inject able

ALbumin Human - AHFS 16:00Products Albumin human is available in 20-, 50-, and 100-mL vials as a 25% aqueous solution. Each 100 mL of solution contains 25 g of serum albumin. Albumin human is also available as a 5% aqueous solution in 50-, 250-, 500-, and 1000-mL sizes. The products also contain sodium carbonate, sodium bicarbonate, sodium hydroxide, and/or acetic acid to adjust the pH. (1-1/05) (4) The products are heat-treated for inactivation of hepatitis viruses. Sodium caprylate and sodium N-acetyltryptophanate are added to the products as stabilizers to prevent denaturation during the heat treatment. Low aluminum-containing albumin human products contain less than 200 mcg/L of aluminum. (1-1/05)

pH From 6.4 to 7.4. (1-1/05) (4)

Sodium Content From 130 to 160 mEq/L. (1-1/05) (4)

Trade Name(s) Albuminar, Albutein, Albumarc, Buminate, Plasbumin

Administration Albumin human is administered intravenously either undiluted or diluted in an intravenous infusion solution having sufficient osmolality to be safely administered. See Infusion Solutions below. (1-1/05) (4)

Stability Albumin human has been variously described as clear amber to deep orange-brown and as a transparent or slightly opalescent pale straw to dark brown solution. The solution should not be used if it is turbid or contains a deposit. Since it contains no preservative, the manufacturer recommends use within four hours after opening the vial. The expiration date is five years after issue from the manufacturer if the labeling recommends storage between 2 and 8 or 10 C, or not more than three years after issue from the manufacturer if the labeling recommends storage at temperatures not greater than 30 or 37 C. (4)

Freezing Solutions Freezing the albumin human solutions may damage the container and result in contamination. (4) Exposure of albumin human to elevated temperatures of 55 and 70 C results in increased degradation, including an increase in dimer formation and aggregation. (2295)

Compatibility Information

Solution Compatibility

Albumin human

=========================================================================== Solution Mfr Mfr Conc/L Remarks Ref C/I =========================================================================== Dextran 6% in AB 5 g Physically compatible 3 C dextrose 5% --------------------------------------------------------------------------- Dextran 6% in AB 5 g Physically compatible 3 C sodium chloride 0.9% --------------------------------------------------------------------------- Dextrose- AB 5 g Physically compatible 3 C Ringer's injection combinations --------------------------------------------------------------------------- Dextrose- AB 5 g Physically

compatible 3 C Ringer's injection, lactated, combinations --------------------------------------------------------------------------- Dextrose- AB 5 g Physically compatible 3 C saline combinations --------------------------------------------------------------------------- Dextrose 2.5% AB 5 g Physically compatible 3 C --------------------------------------------------------------------------- Dextrose 5% AB 5 g Physically compatible 3 C --------------------------------------------------------------------------- Dextrose 10% AB 5 g Physically compatible 3 C --------------------------------------------------------------------------- Fructose 10% AB 5 g Physically compatible 3 C in sodium chloride 0.9% --------------------------------------------------------------------------- Fructose 10% AB 5 g Physically compatible 3 C --------------------------------------------------------------------------- Invert sugar 5 AB 5 g Physically compatible 3 C and 10% in sodium chloride 0.9% --------------------------------------------------------------------------- Invert sugar 5 AB 5 g Physically compatible 3 C and 10% --------------------------------------------------------------------------- Ionosol AB 5 g Physically compatible 3 C products (unless otherwise noted) --------------------------------------------------------------------------- Ionosol D-CM AB 5 g Haze or precipitate 3 I forms within 24 hr --------------------------------------------------------------------------- Ringer's AB 5 g Physically compatible 3 C injection --------------------------------------------------------------------------- Ringer's AB 5 g Physically compatible 3 C injection, lactated --------------------------------------------------------------------------- Sodium AB 5 g Physically compatible 3 C chloride 0.45% --------------------------------------------------------------------------- Sodium AB 5 g Physically compatible 3 C chloride 0.9% --------------------------------------------------------------------------- Sodium lactate AB 5 g Physically compatible 3 C (1/6) M --------------------------------------------------------------------------- TNA #232a 9.5 g Microscopically observed 2267 ? emulsion disruption found with increased fat globule size in 48 hr at room temperature --------------------------------------------------------------------------- TNA #233a 9.5 g Visually apparent 2267 I emulsion disruption with creaming in as little as 4 hr at room temperature. Increased disruption attributed to the added effect of calcium and magnesium ions --------------------------------------------------------------------------- TNA #234a 18.2 g Creaming and free oil 2267 I formation visually observed in 24 hr at room temperature --------------------------------------------------------------------------- TNA #235a 18.2 g Visually apparent 2267 I emulsion disruption with creaming and free oil formation in as little as 4 hr at room temperature. Increased disruption attributed to the added effect of calcium and magnesium ions --------------------------------------------------------------------------- aRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3-in-1 admixture.

Additive Compatibility

Albumin human

========================================================================== Drug Mfr Conc/L Mfr Conc/L Test Remarks Ref C/I Soln ========================================================================== Verapamil KN 80 mg ARC 25 g D5W, NS Cloudiness 764 I HCl develops within 8 hr --------------------------------------------------------------------------

Y-Site Injection Compatibility (1:1 Mixture)

Albumin human

========================================================================================== Drug Mfr Conc Mfr Conc Remarks Ref C/I ========================================================================================== Diltiazem HCl MMD 5 mg/mL AR, AT 5 and Visually compatible 1807 C 25% ------------------------------------------------------------------------------------------ Drotrecogin LI 0.1 and BA 25% Physically compatible 2615 ? alfa 1 mg/ but the pH was outside (activated) mLb the optimal range of drotrecogin alfa (activated) ------------------------------------------------------------------------------------------ Fat emulsion, 20% 20% Emulsion destabilization 2267 I intravenous was evident (Intralipid) immediately ------------------------------------------------------------------------------------------ Lorazepam WY 0.33 mg/ 200 mg/ Visually compatible for 1855 C mLb mL 24 hr at 22 C ------------------------------------------------------------------------------------------ Micafungin ASP 1.5 mg/ ZLB 25% Immediate increase in 2683 I sodium mLb measured haze ------------------------------------------------------------------------------------------ Midazolam HCl RC 5 mg/mL 200 mg/ White precipitate forms 1855 I mL immediately ------------------------------------------------------------------------------------------ Vancomycin HCl 20 mg/ 0.1 and Heavy turbidity forms 1701 I mLa 1%b immediately and precipitate develops subsequently ------------------------------------------------------------------------------------------ Verapamil HCl LY 0.2 mg/ HY 250 mg/ Slight haze in 1 hr 1316 I mLa mLa LY 0.2 mg/ HY 250 mg/ Slight haze in 3 hr 1316 I mLb mLb ------------------------------------------------------------------------------------------ aTested in dextrose 5%. bTested in sodium chloride 0.9%.

Additional Compatibility Information

Infusion Solutions Dextrose 5%, dextrose 10%, and sodium chloride 0.9% have been recommended as infusion vehicles. Albumin human has been stated to be compatible with whole blood, plasma, and sodium lactate solutions as well as dextrose and sodium chloride injections. (4)

CAUTION-Substantial reduction in tonicity, creating the potential for fatal hemolysis and acute renal failure, may result from the use of sterile water as a diluent. The hemolysis and acute renal failure that result from the use of a sufficient volume of sterile water as a diluent may be life-threatening. (4) (1942) (2072) (2073)

Parenteral Nutrition Solutions The addition of albumin human to parenteral nutrition solutions appears to result in visually compatible admixtures for 24 hours. However, occlusion of filters has occurred if the albumin human concentration exceeded 25 g/L (854) and, occasionally, even at concentrations of 19.4 and 10.8 g/L. (1634) Snyder studied the filtration of albumin human 25%, from several suppliers, through 0.22-m filters using a syringe pump. Four products were filtered over 20 minutes, but the Armour product activated the occlusion alarm after only 3.2 minutes. Use of albumin human from suppliers other than Armour in parenteral nutrition solutions resulted in no additional occlusions or flow problems. (1634) However, Feldman and

Bergman noted that although all U.S. manufacturers of albumin human and other plasma proteins use the same cold-alcohol fractionation process, batch-to-batch variations in polymer content occur within all manufacturers' products. Furthermore, parenteral nutrition solution composition, additives, filter composition, and kind of pump may affect flow rates as much as differences in batches or manufacturers. (1635)

Albumin human has also been found to increase the potential of parenteral nutrition solutions to support the growth of fungi and bacteria. Administration of albumin human separately was recommended. (573)

References

For a list of references cited in the text of this monograph, search the monograph titled HID references.

© 2009 American Society of Health-System Pharmacists, Inc. All rights reserved. (+/-) Show / Hide Bibliography RefWorks Citation

Author: o LAWRENCE A. TRISSEL, F.A.S.H.P.

Copyright: o © 2009 American Society of Health-System Pharmacists, Inc. All rights reserved.

Database Title: o STAT!Ref Online Electronic Medical Library

ISBN: o ISBN-13: 978-1-58528-213-5

Publication City: o Bethesda, MD

Publication Year: o 2008

Publisher: o American Society of Health-System Pharmacists

Title: o Handbook on Injectable Drugs - 15th Ed. (2009)

Date Posted: o 2/3/2009 3:41:18 PM PST (GMT -08:00)

Electronic Address: o http://online.statref.com/document.aspx?fxid=141&docid=8

Date Accessed: o 7/28/2009 9:21:47 PM PST (GMT -08:00)

Location In Title: o HANDBOOK ON INJECTABLE DRUGS - 15th Ed. (2009)

"A" Monographs Albumin Human - AHFS 16:00

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Ampicillin Sodium-Sulbactam Sodium - AHFS 8:12.16.08

Products Ampicillin sodium-sulbactam sodium is available in vials and piggyback bottles containing 1.5 g (ampicillin 1 g plus sulbactam 0.5 g) or 3 g (ampicillin 2 g plus sulbactam 1 g) as the sodium salts. (1-7/05)

For intramuscular injection, reconstitute vials with sterile water for injection or lidocaine hydrochloride 0.5 or 2% in the following amounts (1-7/05) :

aSufficient excess is present to permit withdrawal of the volume noted.bAmpicillin 250 mg plus sulbactam 125 mg per milliliter.

==================================================== Vial Size Volume of Withdrawable Concentration Diluent Volume ==================================================== 1.5 g 3.2 mL 4 mLa 375 mg/mLb ---------------------------------------------------- 3.0 g 6.4 mL 8 mLa 375 mg/mLb ----------------------------------------------------

For intravenous use, reconstitute piggyback bottles directly with a compatible diluent to the desired concentration between 3 and 45 mg/mL (ampicillin 2 to 30 mg plus sulbactam 1 to 15 mg per milliliter). Standard vials of 1.5 and 3 g may be reconstituted with 3.2 and 6.4 mL of sterile water for injection, respectively, to yield 375-mg/mL solutions (ampicillin 250 mg plus sulbactam 125 mg per milliliter). The reconstituted solution should be diluted immediately in a compatible infusion solution to yield the desired concentration between 3 and 45 mg/mL. (1-7/05)

/w EPDw ULLTE4N /w EWAgLSw v31

Allow reconstituted solutions to stand so that any foaming may dissipate before inspecting them visually to ensure complete dissolution. (1-7/05)

pH From 8 to 10. (1-7/05)

Sodium Content Each 1.5 g (ampicillin 1 g plus sulbactam 0.5 g as the sodium salts) contains 5 mEq (115 mg) of sodium. (1-7/05)

Trade Name(s) Unasyn

Administration Ampicillin sodium-sulbactam sodium may be administered by deep intramuscular injection or intravenous injection or infusion. By direct intravenous injection, the drug should be given slowly over at least 10 to 15 minutes. By infusion, it may be diluted in 50 to 100 mL of compatible diluent and infused over 15 to 30 minutes. (1-7/05) (4)

Stability Intact vials of the white to off-white powder should be stored at room temperature. Aqueous solutions are pale yellow to yellow. Dilute solutions are pale yellow to colorless. The manufacturer recommends that intramuscular solutions be used within one hour after preparation. The administration of diluted solutions for intravenous infusion should be completed within eight hours of preparation to ensure that the potency is maintained throughout the infusion. (1-7/05) (4)

Elastomeric Reservoir Pumps Ampicillin sodium-sulbactam sodium solutions in elastomeric reservoir pumps have been stated by the pump manufacturers to be stable for the following time periods refrigerated (REF) or at room temperature (RT) (31) :

============================================ Pump Conc. REF RT Reservoir(s) ============================================ Homepump; 30 + 15 mg/ 3 days - Homepump mLa Eclipse -------------------------------------------- Intermate HPC 10 + 5 mg/ 3 days 2 hr mLa -------------------------------------------- Intermate HPC 30 + 15 mg/ 3 days 2 hr mLa -------------------------------------------- aIn sodium chloride 0.9%. --------------------------------------------

Central Venous Catheter Ampicillin sodium-sulbactam sodium (Pfizer-Roerig) 5 + 2.5 mg/mL in sodium chloride 0.9% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. HPLC analysis was used to evaluate completeness of drug delivery through the catheter and the amount of chlorhexidine removed from the internal lumens. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter. (2335)



Ampicillin sodium-sulbactam sodium

======================================================================= Solution Mfr Mfr Conc/L Remarks Ref C/I ======================================================================= Sodium a PF 20 + 10 Visually compatible 1691 C chloride g with 10% ampicillin 0.9% loss by HPLC in 32 hr at 24 C and 68 hr at 5 C ----------------------------------------------------------------------- aTested in PVC containers.



================================================================================================ Drug Mfr Conc/L Mfr Conc/L Test Remarks Ref C/I Soln ================================================================================================ Aztreonam SQ 10 g PF 20 + 10 NSa Visually compatible with 1691 C g 10% ampicillin loss by HPLC in 30 hr at 24 C and 94 hr at 5 C. Ampicillin loss is determining factor ------------------------------------------------------------------------------------------------ Ciprofloxacin MI 2 g 20 + 10 D5W Physically incompatible 888 I g BAY 2 g RR 20 + 10 D5W Immediate precipitation 2413 I g ------------------------------------------------------------------------------------------------ Tramadol HCl GRU 0.4 g PF 20 + 10 NS Visually compatible with up 2652 C g to 9% tramadol loss in 24 hr at room temperature ------------------------------------------------------------------------------------------------ aTested in PVC containers.



========================================================================================================== Drug Mfr Conc Mfr Conc Remarks Ref C/I ========================================================================================================== Amifostine USB 10 mg/mLa WY 20 + 10 mg/ Physically compatible with no 1845 C mLb change in measured turbidity or increase in particle content in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Amiodarone HCl WY 6 mg/mLa PF 30 mg/mLb Immediate opaque white turbidity 2352 I ---------------------------------------------------------------------------------------------------------- Amphotericin B SEQ 0.83 mg/ RR 20 + 10 mg/ Gross precipitate forms 2117 I cholesteryl mLa mLb sulfate complex ---------------------------------------------------------------------------------------------------------- Anidulafungin VIC 0.5 mg/mLa LE 20 + 10 mg/ Physically compatible with no 2617 C mLb change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------

Aztreonam SQ 40 mg/mLa RR 20 + 10 mg/ Physically compatible with no 1758 C mLb subvisual haze or particle formation in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Bivalirudin TMC 5 mg/mLa PF 20 + 10 mg/ Physically compatible with no 2373 C mLb increase in measured haze or particle content in 4 hr at 23 C under fluorescent light ---------------------------------------------------------------------------------------------------------- Cefepime HCl BMS 20 mg/mLa RR 20 + 10 mg/ Physically compatible with no 1689 C mLa change in measured turbidity or increase in particle content in 4 hr at 22 C ---------------------------------------------------------------------------------------------------------- Ciprofloxacin 400 mgc 3 + 1.5 gc Administered sequentially 1887 I through a Y-site into running D5S. White crystals formed immediately ---------------------------------------------------------------------------------------------------------- Cisatracurium GW 0.1 and 2 RR 20 + 10 mg/ Physically compatible with no 2074 C besylate mg/mLa mLb change in measured turbidity or increase in particle content in 4 hr at 23 C GW 5 mg/mLa RR 20 + 10 mg/ Subvisual haze develops in 15 2074 I mLb min ---------------------------------------------------------------------------------------------------------- Dexmedetomidine AB 4 g/mLb PF 20 + 10 mg/ Physically compatible with no 2383 C HCl mLb

increase in measured haze or particle content in 4 hr at 23 C under fluorescent light ---------------------------------------------------------------------------------------------------------- Diltiazem HCl MMD 5 mg/mL RR 45 + 22.5 Cloudiness forms 1807 I mg/mLb MMD 1 mg/mLb

RR 45 + 22.5 Visually compatible 1807 C mg/mLb MMD 5 mg/mL RR 15 + 7.5 mg/ Visually compatible 1807 C mLb MMD 5 mg/mL RR 2 + 1 mg/mLb Visually compatible 1807 C ---------------------------------------------------------------------------------------------------------- Docetaxel RPR 0.9 mg/mLa RR 20 + 10 mg/ Physically compatible with no 2224 C mLb change in measured turbidity or increase in particle content in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Drotrecogin alfa LI 0.1 and 1 PF 30 + 15 mg/ Physically compatible but the pH 2615 ? (activated) mg/mLb mLb was outside the optimal range of drotrecogin alfa (activated) ---------------------------------------------------------------------------------------------------------- Enalaprilat MSD 0.05 mg/ PF 10 + 5 mg/ Physically compatible for 24 hr 1355 C mLb mLb at room temperature under fluorescent light ---------------------------------------------------------------------------------------------------------- Etoposide BR 5 mg/mLa RR 20 + 10 mg/ Physically compatible with no 2218 C phosphate mLb change in measured turbidity or increase in particle content in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Famotidine MSD 0.2 mg/mLa RR 20 + 10 mg/ Physically compatible for 14 hr 1196 C mLb ---------------------------------------------------------------------------------------------------------- Fenoldopam AB 80 g/mLb PF 20 + 10 mg/ Physically compatible with no 2467 C mesylate mLb

increase in measured haze or particle content in 4 hr at 23 C under fluorescent light ---------------------------------------------------------------------------------------------------------- Filgrastim AMG 30 g/mLa RR 20 + 10 mg/ Physically compatible with no 1687 C mLa change in measured turbidity or increase in particle content in 4 hr at 22 C ---------------------------------------------------------------------------------------------------------- Fluconazole RR 2 mg/mL RR 40 + 20 mg/ Physically compatible for 24 hr 1407 C mL at 25 C ---------------------------------------------------------------------------------------------------------- Fludarabine BX 1 mg/mLa RR 20 + 10 mg/ Physically compatible for 4 hr 1439 C phosphate

mLb at room temperature under fluorescent light ---------------------------------------------------------------------------------------------------------- Gallium nitrate FUJ 1 mg/mLb RR 45 + 22.5 Visually compatible for 24 hr at 1673 C mg/mLb 25 C ---------------------------------------------------------------------------------------------------------- Gemcitabine HCl LI 10 mg/mLb RR 20 + 10 mg/ Physically compatible with no 2226 C mLb change in measured turbidity or increase in particle content in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Granisetron HCl SKB 0.05 mg/ RR 20 + 10 mg/ Physically compatible with no 2000 C mLa mLb change in measured turbidity or increase in particle content in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Heparin sodium TR 50 units/ PF 20 + 10 mg/ Visually compatible for 4 hr at 1793 C mL mLb 25 C ---------------------------------------------------------------------------------------------------------- Hetastarch in AB 6% PF 20 + 10 mg/ Physically compatible with no 2339 C lactated mLb change in measured turbidity electrolyte or increase in particle injection content in 4 hr at 23 C (Hextend) ---------------------------------------------------------------------------------------------------------- Idarubicin HCl AD 1 mg/mLb RR 20 + 10 mg/ Haze forms and color changes 1525 I mLb immediately. Precipitate forms within 20 min ---------------------------------------------------------------------------------------------------------- Insulin, regular LI 0.2 unit/ RR 20 + 10 mg/ Physically compatible for 2 hr 1395 C mLb mLb at 25 C ---------------------------------------------------------------------------------------------------------- Linezolid PHU 2 mg/mL PF 20 + 10 mg/ Physically compatible with no 2264 C mLb change in measured turbidity or increase in particle content in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Meperidine HCl WY 10 mg/mLb RR 20 + 10 mg/ Physically compatible for 1 hr 1338 C mLb at 25 C ---------------------------------------------------------------------------------------------------------- Morphine sulfate ES 1 mg/mLb RR 20 + 10 mg/ Physically compatible for 1 hr 1338 C mLb at 25 C ---------------------------------------------------------------------------------------------------------- Nicardipine HCl DCC 0.1 mg/ PF 10 + 5 mg/ Turbidity forms immediately 235 I mLab mLab ---------------------------------------------------------------------------------------------------------- Ondansetron HCl GL 1 mg/mLb RR 20 + 10 mg/ Immediate turbidity and 1365 I mLb precipitation ---------------------------------------------------------------------------------------------------------- Paclitaxel NCI 1.2 mg/mLa RR 20 + 10 mg/ Physically compatible with no 1556 C mLb change in measured turbidity in 4 hr at 22 C ---------------------------------------------------------------------------------------------------------- Pemetrexed LI 20 mg/mLb LED 20 + 10 mg/ Physically compatible with no 2564 C disodium mLb change in measured turbidity or increase in particle content in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Remifentanil HCl GW 0.025 and RR 20 + 10 mg/ Physically compatible with no 2075 C 0.25 mg/ mLb change in measured turbidity mLb or increase in particle content in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Sargramostim IMM 10 g/mLb RR 20 + 10 mg/ Few small particles in 4 hr in 1436 I mLb one of two samples ---------------------------------------------------------------------------------------------------------- Tacrolimus FUJ 1 mg/mLb RR 33.3 + 16.7 Visually compatible for 24 hr at 1630 C mg/mLa 25

C ---------------------------------------------------------------------------------------------------------- Teniposide BR 0.1 mg/mLa RR 20 + 10 mg/ Physically compatible with no 1725 C mLb subvisual haze or particle formation in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Theophylline TR 4 mg/mL PF 20 + 10 mg/ Visually compatible for 6 hr at 1793 C mLb 25 C ---------------------------------------------------------------------------------------------------------- Thiotepa IMMd 1 mg/mLa RR 20 + 10 mg/ Physically compatible with no 1861 C mLb change in measured turbidity or increase in particle content in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- TNA #218 to #226e PF 20 + 10 mg/ Visually compatible with no 2215 C mLb precipitate or emulsion damage apparent in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- TPN #212 to #215e RR 20 + 10 mg/ Physically compatible with no 2109 C mLb change in measured turbidity or increase in particle content in 4 hr at 23 C ---------------------------------------------------------------------------------------------------------- Vancomycin HCl AB 20 mg/mLa PF 250 + 125 Transient precipitate forms, 2189 ? mg/mLf followed by clear solution AB 20 mg/mLa PF 1 + 0.5, 10 Physically compatible with no 2189 C + 5, and change in measured turbidity 50 + 25 or increase in particle mg/mLb content in 4 hr at 23 C AB 2 mg/mLa PF 1 + 0.5b, 10 Physically compatible with no 2189 C + 5b, 50 + change in measured turbidity 25b, and or increase in particle 250 + 125f content in 4 hr at 23 C mg/mL ---------------------------------------------------------------------------------------------------------- aTested in dextrose 5%. bTested in sodium chloride 0.9%. cConcentration and volume not specified. dLyophilized formulation tested. eRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3- in-1 admixture, and TPN indicates a 2-in-1 admixture. fTested in sterile water for injection.


The compatibility information on ampicillin sodium should be considered. See previous monograph.

Infusion Solutions The manufacturer recommends the following use periods for ampicillin sodium-sulbactam sodium diluted in the infusion solutions noted (1-7/05) :

===================================================== Infusion Maximum Storage Use Solution Concentration Temperature Period (mg/mL) (C) (hr) (Ampicillin/ Sulbactam) ===================================================== Dextrose 5% in 3 (2/1) 25 4 sodium 15 (10/5) 4 4 chloride 0.45% ----------------------------------------------------- Dextrose 5% 30 (20/10) 25 2 ----------------------------------------------------- 30 (20/10) 4 4 ----------------------------------------------------- 3 (2/1) 25 4 ----------------------------------------------------- Invert sugar 3 (2/1) 25 4 10% ----------------------------------------------------- 30 (20/10) 4 3 ----------------------------------------------------- Ringer's 45 (30/15) 25 8 injection, 45 (30/15) 4 24 lactated ----------------------------------------------------- Sodium 45 (30/15) 25 8 chloride 0.9% ----------------------------------------------------- 45 (30/15) 4 48 ----------------------------------------------------- 30 (20/10) 4 72

----------------------------------------------------- Sodium lactate 45 (30/15) 25 8 (1/6) M ----------------------------------------------------- 45 (30/15) 4 8 ----------------------------------------------------- Sterile water 45 (30/15) 25 8 forinjection 45 (30/15) 4 48 30 (20/10) 4 72 -----------------------------------------------------

Aminoglycosides The manufacturer indicates that ampicillin sodium-sulbactam sodium should be reconstituted and administered separately from aminoglycosides because of possible in vitro inactivation. (1-7/05)

Vancomycin The compatibility or incompatibility of vancomycin hydrochloride mixed with or administered simultaneously with ampicillin sodium-sulbactam sodium may be concentration dependent. (2189) See Y-Site Compatibility above. Vancomycin hydrochloride has a low pH and is variably compatible with drugs having neutral to mildly alkaline pH, including cephalosporins and penicillins. The compatibility may depend on a number of factors, including concentration of each drug, dilution vehicle, actual pH of solutions, and completeness of mixing during administration. Combinations that are compatible when well mixed may result in precipitation if only partially mixed, presumably because of regionally different concentrations and pH values. If attempting to administer vancomycin hydrochloride with ampicillin sodium-sulbactam sodium, take care to ensure that the specific combination and the concentrations are compatible under the exact administration conditions to be used. An inline filter should be used as a final safety measure. (2189)

References






ISBN: o ISBN-13: 978-1-58528-213-5









"A" Monographs Ampicillin Sodium-Sulbactam Sodium - AHFS 8:12.16.08


Cefotaxime Sodium - AHFS 8:12.06.12

Products Cefotaxime sodium is available in vials containing the equivalent of 500 mg and 1 and 2 g of cefotaxime (as sodium) and in infusion bottles containing the equivalent of 1 g of cefotaxime (as sodium). It is also available in 10- and 20-g pharmacy bulk packages. (1-11/04)

For intravenous administration, the contents of any size vial may be reconstituted with 10 mL of sterile water for injection. (See Table 1.) The 1- and 2-g infusion bottles may be reconstituted with 50 or 100 mL of dextrose 5% or sodium chloride 0.9%. For intramuscular injection, reconstitute with sterile water for injection or bacteriostatic water for injection in the amounts shown in Table 1. (1-11/04)

Table 1. Recommended Reconstitution of Cefotaxime Sodium 1-11/04

======================================================== Vial Size Volume of Withdrawable Approximate Diluent Volume Concentration


======================================================== Intravenous -------------------------------------------------------- 500 mg 10 mL 10.2 mL 50 mg/mL -------------------------------------------------------- 1 g 10 mL 10.4 mL 95 mg/mL -------------------------------------------------------- 2 g 10 mL 11.0 mL 180 mg/mL -------------------------------------------------------- Intramuscular -------------------------------------------------------- 500 mg 2 mL 2.2 mL 230 mg/mL -------------------------------------------------------- 1 g 3 mL 3.4 mL 300 mg/mL -------------------------------------------------------- 2 g 5 mL 6.0 mL 330 mg/mL --------------------------------------------------------

The pharmacy bulk packages may be reconstituted according to the manufacturer's directions, and the dose should be diluted appropriately for administration. (1-11/04) (4)

After addition of the diluent, shake to dissolve the contents and inspect for particulate matter or discoloration. (1-11/04)

For intravenous infusion, the primary solution may be diluted further to 50 to 1000 mL in a compatible diluent. (1-11/04) (See Additional Compatibility Information.)

Cefotaxime sodium is also available as a frozen premixed iso-osmotic infusion solution of 1 or 2 g in dextrose 3.4 or 1.4%, respectively, buffered with sodium citrate. Hydrochloric acid and sodium hydroxide, if needed, are used to adjust the pH during manufacturing. (1-11/04) (4)

pH Injectable solutions of the drug have pH values ranging from 5 to 7.5. (1-11/04)

Osmolality A solution of cefotaxime sodium 1 g/14 mL of sterile water for injection is isotonic. (1-11/04)

The osmolality of cefotaxime sodium 1, 2, and 3 g was calculated for the following dilutions (1054) :

================================== Osmolality (mOsm/kg) Diluent 50 mL 100 mL ================================== 1 g ---------------------------------- Dextrose 5% 350 319 ---------------------------------- Sodium 375 344 chloride 0.9% ---------------------------------- 2 g ---------------------------------- Dextrose 5% 343 327 ---------------------------------- Sodium 406 351 chloride 0.9% ---------------------------------- 3 g ---------------------------------- Dextrose 5% 433 344 ---------------------------------- Sodium 458 382 chloride 0.9% ----------------------------------

The frozen premixed solutions have osmolalities of 340 to 420 mOsm/kg for the 1-g/50 mL concentration and 450 to 540 mOsm/kg for the 2-g/50 mL concentration. (4)

The osmolality of cefotaxime sodium (Hoechst) 50 mg/mL was determined to be 326 mOsm/kg in dextrose 5% and 333 mOsm/kg in sodium chloride 0.9%. (1375)

Robinson et al. recommended the following maximum cefotaxime sodium concentrations to achieve osmolalities suitable for peripheral infusion in fluid-restricted patients (1180) :

========================================== Diluent Maximum Osmolality Concentration (mOsm/kg) (mg/mL) ========================================== Dextrose 5% 86 577 ------------------------------------------ Sodium 73 555 chloride 0.9% ------------------------------------------ Sterile water 147 525 for injection ------------------------------------------

Sodium Content Cefotaxime sodium contains approximately 2.2 mEq (50.5 mg) of sodium per gram of cefotaxime activity. (1-11/04)

Trade Name(s) Claforan

Administration Cefotaxime sodium may be administered by deep intramuscular injection; doses of 2 g should be divided between different injection sites. It may also be administered by direct intravenous injection over three to five minutes directly into the vein or into the tubing of a running compatible infusion solution. In addition, cefotaxime sodium may be administered in 50 to 100 mL of compatible diluent over 20 to 30 minutes by intermittent intravenous infusion or by continuous intravenous infusion. (1-11/04) (4) (8)

Stability Intact vials of cefotaxime sodium (Aventis) should be stored below 30 C. The dry powder is off-white to pale yellow in color. Solutions may range from light yellow to amber, depending on the diluent, concentration, and storage conditions. Both the dry material and solutions may darken and should be protected from elevated temperatures and excessive light. Discoloration of the powder or solution may indicate a loss of potency. (1-11/04) (4)

Store the frozen premixed cefotaxime sodium infusions at -20 C or below. Thaw at room temperature or under refrigeration. Accelerated thawing using water bath immersion or microwave irradiation should not be used. Thawed solutions should not be refrozen. (1-11/04) (4)

When reconstituted as described in the Products section, cefotaxime sodium (Aventis) is stable in the original containers as indicated in Table 2. Storage of reconstituted solutions in disposable glass or plastic syringes for five days under refrigeration is also recommended. Dilutions of cefotaxime sodium in dextrose 5% or sodium chloride 0.9% in PVC bags are also stable for 24 hours at room temperature or five days under refrigeration. (1-11/04)

Table 2. Manufacturer's Recommended Storage Times of Reconstituted Cefotaxime Sodium 1-11/04

================================================ Storage Temperature Vial Size Concentration 22 C 5 C ================================================ 500 mg 230 mg/mL 12 hr 7 days ------------------------------------------------ 50 mg/mL 24 hr 7 days ------------------------------------------------ 1 g 300 mg/mL 12 hr 7 days ------------------------------------------------ 95 mg/mL 24 hr 7 days ------------------------------------------------ (Infusion 10 to 20 mg/mL 24 hr 10 days bottle) ------------------------------------------------ 2 g 330 mg/mL 12 hr 7 days

------------------------------------------------ 180 mg/mL 12 hr 7 days ------------------------------------------------ (Infusion 20 to 40 mg/mL 24 hr 10 days bottle) ------------------------------------------------

Cefotaxime sodium (Hoechst-Roussel) 1 g/10 mL reconstituted with sterile water for injection or 1 g/50 mL in dextrose 5% in PVC bags exhibited no visible changes in 24 hours at 5 and 25 C. Although increased levels of particulate matter were observed in most solutions, the increases were significant only in solutions stored at 25 C. (986)

pH Effects The primary factor in the stability of cefotaxime sodium is solution pH. (792) Cefotaxime sodium in aqueous solutions is stable at pH 5 to 7 (1-11/04) or 4.3 to 6.2. (1077) The theoretical pH of minimum decomposition is 5.13. (793) However, between pH 3 and 7, the hydrolysis rate is virtually independent of pH. (1072) Determination of decomposition kinetics in various aqueous buffer systems at 25 C showed 10% decomposition occurring in 24 hours or longer over a pH range of 3.9 to 7.6. At pH 2.2 and 8.4, 10% decomposition occurred in about 13 hours. (793)

The manufacturer recommends that cefotaxime sodium not be diluted in solutions with a pH greater than 7.5. (1-11/04) (4)

Freezing Solutions When reconstituted as recommended, cefotaxime sodium may be stored frozen in the vial or in disposable glass or plastic syringes for 13 weeks. Similarly, dilutions of cefotaxime sodium in dextrose 5% or sodium chloride 0.9% in PVC bags may be stored frozen for 13 weeks. Thawing at room temperature is recommended; frozen solutions should not be heated. Once thawed, the solutions are stable for 24 hours at room temperature or five days at less than 5 C. Thawed solutions should not be refrozen. (1-11/04) (4)

In one study, cefotaxime sodium (Hoechst-Roussel) 10 g/L in PVC bags of dextrose 5% and sodium chloride 0.9% (Travenol) exhibited no decomposition after 63 days of storage at -10 C. (751)

Syringes Cefotaxime sodium (Roussel) 250 mg/mL in sterile water for injection, packaged as 0.18 mL in 1-mL Injekt syringes (Braun) sealed with blind hubs and stored at about 6 C, retained antibiotic activity against Pseudomonas aeruginosa for seven days. However, the yellow color of the solution became much darker over this period. (1697)

Cefotaxime sodium (Aventis) 50 mg/mL in sodium chloride 0.9% packaged in 5-mL polypropylene plastic syringes is visually compatible and undergoes about 10% loss by HPLC in 2 days at 25 C and about 3% loss in 18 days at 5 C. (2371)

Elastomeric Reservoir Pumps Cefotaxime sodium solutions in elastomeric reservoir pumps have been stated by the pump manufacturers to be stable for the following time periods frozen, refrigerated (REF), or at room temperature (RT) (31) :

======================================================= Pump Conc. Frozen REF RT Reservoir(s) ======================================================= Homepump; 16.66

mg/ - - 24 hr Homepump mLb Eclipse ------------------------------------------------------- Intermate 40 mg/mLb 30 days 10 days 24 hr ------------------------------------------------------- Medflo 20 mg/mLa 13 weeks 22 days 48 hr ------------------------------------------------------- ReadyMed 10 mg/mLa - 22 days 24 hr ------------------------------------------------------- 20 mg/mLb 4 weeks 14 days 48 hr ------------------------------------------------------- aIn dextrose 5%. bIn sodium chloride 0.9%. -------------------------------------------------------

Sorption Cefotaxime sodium (Aventis) 50 mg/mL in sodium chloride 0.9% packaged in polypropylene plastic syringes exhibited no evidence of sorption when compared to glass containers. (2371)

Central Venous Catheter Cefotaxime sodium (Hoechst-Roussel) 5 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. HPLC analysis was used to evaluate completeness of drug delivery through the catheter and the amount of chlorhexidine removed from the internal lumens. Delivery of the cefotaxime sodium ranged from 93 to 95% of the initial concentration among the three lumens. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter. (2335)



Cefotaxime sodium

================================================================================= Solution Mfr Mfr Conc/L Remarks Ref C/I ================================================================================= Dextrose TRa HO 10 g Physically compatible with 3% 751 1077 C 5% decomposition in 24 hr at 24 C. No decomposition in 22 days at 4 C --------------------------------------------------------------------------------- Dextrose ABb HO 20 g Physically compatible with 994 C 5% little or no cefotaxime loss in 24 hr at 25 C --------------------------------------------------------------------------------- Sodium TRa HO 10 g Physically compatible with 2% 751 1077 C chloride decomposition in 24 hr at 24 0.9% C. No decomposition in 22 days at 4 C --------------------------------------------------------------------------------- Sodium ABb HO 20 g Physically compatible with 994 C chloride little or no cefotaxime loss 0.9% in 24 hr at 25 C --------------------------------------------------------------------------------- TPN #107c 1 g Cefotaxime activity retained 1326 C for 24 hr at 21 C by microbiological assay --------------------------------------------------------------------------------- aTested in PVC containers. bTested in both glass bottles and PVC bags. cRefer to Appendix I for the composition of parenteral nutrition solutions. TPN indicates a 2-in-1 admixture.


Cefotaxime sodium

======================================================================================================== Drug Mfr Conc/L Mfr Conc/L Test Remarks Ref C/I Soln ======================================================================================================== Amikacin BR 25 mg RS 50 mg D5W About 33% loss of amikacin in 2 504 I sulfate hr at 22 C by microbiological assay BR 15 mg RS 50 mg D5W Less than 8% loss of amikacin in 504 C 24 hr at 22 C by microbiological assay -------------------------------------------------------------------------------------------------------- Clindamycin UP 9 g HO 20 g D5W, Physically compatible with no 994 C phosphate NSa clindamycin loss and 3% cefotaxime loss in 24 hr at 25 C -------------------------------------------------------------------------------------------------------- Fusidate sodium LEO 500 mg 2.5 g D-S Physically compatible and 1800 C chemically stable for 48 hr at room temperature -------------------------------------------------------------------------------------------------------- Gentamicin SC 9 mg RS 50 mg D5W About 30% loss of gentamicin in 2 504 I sulfate hr at 22 C by microbiological assay SC 6 mg RS 50 mg D5W Less than 4% loss of gentamicin 504 C in 24 hr at 22 C by microbiological assay -------------------------------------------------------------------------------------------------------- Metronidazole RP 5 gb RS 20 g Physically compatible with little 807 C or no pH change for at least 24 hr at 4 C AB 5 g HO 10 g Potency of both drugs by HPLC 1547 C retained for 72 hr at 8 C AB 5 g HO 10 g Visually compatible with 10% 1754 C cefotaxime loss by HPLC in 19 hr at 28 C and 8% loss in 96 hr at 5 C. No metronidazole loss in 96 hr at 5 or 28 C -------------------------------------------------------------------------------------------------------- Verapamil HCl KN 80 mg HO 4 g D5W, NS Physically compatible for 24 hr 764 C -------------------------------------------------------------------------------------------------------- aTested in both glass and PVC containers. bMinibags (100 mL) containing metronidazole 500 mg with disodium phosphate 150 mg, citric acid 44 mg, and sodium chloride 740 mg. This product differs from the Searle product.

Drugs in Syringe Compatibility

Cefotaxime sodium

======================================================================================= Drug (in Mfr Amt Mfr Amt Remarks Ref C/I syringe) ======================================================================================= Caffeine citrate 20 mg/1 HO 200 mg/ Visually compatible 2440 C mL 1 mL for 4 hr at 25 C --------------------------------------------------------------------------------------- Dimenhydrinate 10 mg/1 100 mg/ Clear solution 2569 C mL 1 mL --------------------------------------------------------------------------------------- Doxapram HCl RB 400 mg/20 500 mg/ Immediate 1177 I mL 4 mL precipitation --------------------------------------------------------------------------------------- Heparin sodium 2500 HO 2 g Physically compatible 1053 C units/1 for at least 5 min mL --------------------------------------------------------------------------------------- Ofloxacin HO 200 mg HO 2 g Visually compatible 1735 C with no loss of either drug by HPLC in 4 hr at room temperature ---------------------------------------------------------------------------------------

Pantoprazole 4 mg/1 mL 100 mg/ Precipitates 2574 I sodium 1 mL immediately ---------------------------------------------------------------------------------------


Cefotaxime sodium

===================================================================================================== Drug Mfr Conc Mfr Conc Remarks Ref C/I ===================================================================================================== Acyclovir sodium BW 5 mg/mLa HO 20 mg/mLa Physically compatible for 4 hr 1157 C at 25 C ----------------------------------------------------------------------------------------------------- Allopurinol sodium BW 3 mg/mLb HO 20 mg/mLb Tiny particles form immediately 1668 I ----------------------------------------------------------------------------------------------------- Amifostine USB 10 mg/ HO 20 mg/mLa Physically compatible with no 1845 C mLa change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------- Anakinra SYN 4 and 36 HO 10 mg/mLb Physically compatible but 2508 ? mg/mLb uncertain anakinra stability. No cefotaxime loss in 4 hr at 25 C ----------------------------------------------------------------------------------------------------- Azithromycin PF 2 mg/mLb HMR 200 mg/ White microcrystals found upon 2368 I mLij filter inspection ----------------------------------------------------------------------------------------------------- Aztreonam SQ 40 mg/ HO 20 mg/mLa Physically compatible with no 1758 C mLa subvisual haze or particle formation in 4 hr at 23 C ----------------------------------------------------------------------------------------------------- Bivalirudin TMC 5 mg/mLa HO 20 mg/mLa Physically compatible with no 2373 C increase in measured haze or particle content in 4 hr at 23 C under fluorescent light ----------------------------------------------------------------------------------------------------- Cisatracurium GW 0.1 mg/ HO 20 mg/mLa Physically compatible with no 2074 C besylate mLa change in measured turbidity or increase in particle content in 4 hr at 23 C GW 2 mg/mLa HO 20 mg/mLa Subvisual haze forms in 4 hr 2074 I GW 5 mg/mLa HO 20 mg/mLa Subvisual haze forms 2074 I immediately ----------------------------------------------------------------------------------------------------- Cyclophosphamide MJ 20 mg/ HO 20 mg/mLa Physically compatible for 4 hr 1194 C mLa at 25 C ----------------------------------------------------------------------------------------------------- Dexmedetomidine AB 4 g/mLb HO 20 mg/mLb Physically compatible with no 2383 C HCl increase in measured haze or particle content in 4 hr at 23 C under fluorescent light ----------------------------------------------------------------------------------------------------- Diltiazem HCl MMD 5 mg/mL HO 10 and Visually compatible 1807 C 180 mg/ mLb MMD 1 mg/mLb HO 180 mg/ Visually compatible 1807 C mLb ----------------------------------------------------------------------------------------------------- Docetaxel RPR 0.9 mg/ HO 20 mg/mLa Physically compatible with no 2224 C mLa change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------- Etoposide BR 5 mg/mLa HO 20 mg/mLa Physically compatible with no 2218 C phosphate change in measured turbidity or increase in particle content in 4 hr at 23 C

----------------------------------------------------------------------------------------------------- Famotidine MSD 0.2 mg/ HO 20 mg/mLb Physically compatible for 14 hr 1196 C mLa ME 2 mg/mLb 20 mg/mLa Visually compatible for 4 hr at 1936 C 22 C ----------------------------------------------------------------------------------------------------- Fenoldopam AB 80 g/ HO 20 mg/mLb Physically compatible with no 2467 C mesylate mLb increase in measured haze or particle content in 4 hr at 23 C under fluorescent light ----------------------------------------------------------------------------------------------------- Filgrastim AMG 30 g/ HO 20 mg/mLa Particles form in 4 hr 1687 I mLa ----------------------------------------------------------------------------------------------------- Fluconazole RR 2 mg/mL HO 20 mg/mL Cloudiness and amber color 1407 I develop ----------------------------------------------------------------------------------------------------- Fludarabine BX 1 mg/mLa HO 20 mg/mLa Physically compatible for 4 hr 1439 C phosphate at room temperature under fluorescent light ----------------------------------------------------------------------------------------------------- Gemcitabine HCl LI 10 mg/ HO 20 mg/mLb Slight subvisual haze forms in 2226 I mLb 1 hr with increased haze and a subvisual precipitate in 4 hr ----------------------------------------------------------------------------------------------------- Granisetron HCl SKB 0.05 mg/ HO 20 mg/mLa Physically compatible with no 2000 C mLa change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------- Hetastarch in AB 6% HO 20 mg/mLa Physically compatible with no 2339 C lactated change in measured turbidity electrolyte or increase in particle injection content in 4 hr at 23 C (Hextend) ----------------------------------------------------------------------------------------------------- Hetastarch in DCC 6% HO 20 mg/mLa Small crystals formed 1313 I sodium chloride immediately after mixing and 0.9% persisted for 4 hr ----------------------------------------------------------------------------------------------------- Hydromorphone HCl WY 0.2 mg/ HO 20 mg/mLa Physically compatible for at 987 C mLa least 4 hr at 25 C under fluorescent light ----------------------------------------------------------------------------------------------------- Levofloxacin OMN 5 mg/mLa HO 200 mg/mL Visually compatible for 4 hr at 2233 C 24 C under fluorescent light ----------------------------------------------------------------------------------------------------- Lorazepam WY 0.33 mg/ RS 10 mg/mL Visually compatible for 24 hr 1855 C mLb at 22 C ----------------------------------------------------------------------------------------------------- Magnesium sulfate IX 16.7, HO 20 mg/mLa Physically compatible for at 813 C 33.3, least 4 hr at 32 C 66.7, 100 mg/mLa ----------------------------------------------------------------------------------------------------- Melphalan HCl BW 0.1 mg/ HO 20 mg/mLb Physically compatible with no 1557 C mLb change in measured turbidity or increase in particle content in 3 hr at 22 C ----------------------------------------------------------------------------------------------------- Meperidine HCl WY 10 mg/ HO 20 mg/mLa Physically compatible for at 987 C mLa least 4 hr at 25 C under fluorescent light ----------------------------------------------------------------------------------------------------- Midazolam HCl RC 1 mg/mLa HO 20 mg/mLa Visually compatible for 24 hr 1847 C at 23 C RC 5 mg/mL RS 10 mg/mL Visually compatible for 24 hr 1855 C at 22 C ----------------------------------------------------------------------------------------------------- Milrinone lactate SS 0.2 mg/ HO 150 mg/ Visually compatible for 4 hr at 2381 C mLa mLa 25 C

----------------------------------------------------------------------------------------------------- Morphine sulfate WI 1 mg/mLa HO 20 mg/mLa Physically compatible for at 987 C least 4 hr at 25 C under fluorescent light ----------------------------------------------------------------------------------------------------- Ondansetron HCl GL 1 mg/mLb HO 20 mg/mLa Physically compatible for 4 hr 1365 C at 22 C ----------------------------------------------------------------------------------------------------- Pemetrexed LI 20 mg/ APP 20 mg/mLa Slight color darkening occurs 2564 I disodium mLb over 4 hr ----------------------------------------------------------------------------------------------------- Pentamidine FUJ 3 mg/mLa HO 20 mg/mLa Fine precipitate, difficult to 1880 I isethionate see, forms immediately ----------------------------------------------------------------------------------------------------- Propofol ZEN 10 mg/mL HO 20 mg/mLa Physically compatible for 1 hr 2066 C at 23 C with no increase in particle content ----------------------------------------------------------------------------------------------------- Remifentanil HCl GW 0.025 HO 20 mg/mLa Physically compatible with no 2075 C and change in measured turbidity 0.25 or increase in particle mg/mLb content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------- Sargramostim IMM 10 g/ HO 20 mg/mLb Physically compatible for 4 hr 1436 C mLb at 22 C ----------------------------------------------------------------------------------------------------- Teniposide BR 0.1 mg/ HO 20 mg/mLa Physically compatible with no 1725 C mLa subvisual haze or particle formation in 4 hr at 23 C ----------------------------------------------------------------------------------------------------- Thiotepa IMMc 1 mg/mLa HO 20 mg/mLa Physically compatible with no 1861 C change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------- Tigecycline WY 1 mg/mLb 40 mg/mLb Physically compatible for 4 hr 2714 C ----------------------------------------------------------------------------------------------------- TNA #218 to #226d HO 20 mg/mLa Visually compatible with no 2215 C precipitate or emulsion damage apparent in 4 hr at 23 C ----------------------------------------------------------------------------------------------------- TPN #61d e HO 200 mg/ Physically compatible 1012 C 0.7 mLf g HO 1.2 g/4 Physically compatible 1012 C mLf ----------------------------------------------------------------------------------------------------- TPN #189d RS 200 mg/ Visually compatible for 24 hr 1767 C mLe at 22 C ----------------------------------------------------------------------------------------------------- TPN #203 and TPN HO 60 mg/mL Visually compatible for 2 hr at 1974 C #204d 23 C ----------------------------------------------------------------------------------------------------- TPN #212 to #215d HO 20 mg/mLa Physically compatible with no 2109 C change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------- Vancomycin HCl 12.5, 100 mg/ White precipitate forms 1721 I 25, mLh immediately 30, 50 mg/mLh 5 mg/mLh 100 mg/ No precipitate visually 1721 ? mLh observed over 7 days at room temperature, but nonvisual incompatibility cannot be ruled out AB 20 mg/ HO 200 mg/ Transient precipitate forms, 2189 ? mLa mLh followed by clear solution AB 20 mg/ HO 50 mg/mLa White cloudiness forms 2189 I mLa immediately AB 20 mg/ HO 1 and 10 Physically compatible with no 2189 C mLa mg/mLa change in measured turbidity or increase in particle content in 4 hr at 23 C AB 2 mg/mLa HO 1a, 10a, Physically compatible with no 2189 C 50a, change in measured turbidity and or increase in particle 200h content in 4 hr at 23 C mg/mL

----------------------------------------------------------------------------------------------------- Vinorelbine BW 1 mg/mLb HO 20 mg/mLb Physically compatible with 1558 C tartrate little change in measured turbidity or increase in particle content in 4 hr at 22 C ----------------------------------------------------------------------------------------------------- aTested in dextrose 5%. bTested in sodium chloride 0.9%. cLyophilized formulation tested. dRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3- in-1 admixture, and TPN indicates a 2-in-1 admixture. eRun at 21 mL/hr. fGiven over five minutes by syringe pump. gRun at 94 mL/hr. hTested in sterile water for injection. iTested in sodium chloride 0.45%. jInjected via Y-site into an administration set running azithromycin.


Infusion Solutions Cefotaxime sodium maintains potency for 24 hours at room temperature and at least five days under refrigeration diluted in 50 to 1000 mL of the following infusion solutions (1-11/04) :

Amino acids 8.5%

Dextrose 5% in sodium chloride 0.2, 0.45, and 0.9%

Dextrose 5 and 10%

Invert sugar 10%

Ringer's injection, lactated

Sodium chloride 0.9%

Sodium lactate (1/6) M

The manufacturer recommends that additives not be introduced into the premixed cefotaxime sodium in dextrose infusion. (1-11/04)

Peritoneal Dialysis Solutions Cefotaxime sodium 2 mg/mL in peritoneal dialysis solution (McGaw) containing dextrose 2.5% and electrolytes was physically compatible for three hours at room temperature. Furthermore, no significant loss of antibacterial activity was apparent by microbiological determination. (142)

The stability of cefotaxime sodium (Hoechst-Roussel) 125 mg/L in peritoneal dialysis solutions (Dianeal 137 and PD2) with heparin sodium 500 units/L was evaluated at 25 C by microbiological assay. Approximately 95 6% activity remained after 24 hours. (1228)

Paap and Nahata studied the stability of cefotaxime sodium (Hoechst-Roussel) 1 mg/mL in Dianeal PD-1 with dextrose 1.5 and 4.25% (Travenol). At 25 C, the drug exhibited an 8% loss in 24 hours and a 16% loss in 48 hours in both solutions. Storage at 37 C for 12 hours resulted in 11 and 14% losses in the solutions containing dextrose 1.5% and dextrose 4.25%, respectively. (1481)

Alkaline Drugs Cefotaxime sodium should not be mixed in alkaline solutions such as sodium bicarbonate injection (1-11/04) or solutions containing aminophylline. (792)

Aminoglycosides The manufacturer states that cefotaxime sodium should not be admixed with aminoglycosides. (1-11/04) However, they may be administered separately to the same patient. (1-11/04) (792)

No inactivation of tobramycin, gentamicin, and amikacin 10 g/mL was caused by cefotaxime 100 and 500 g/mL when the mixtures were stored at 37 C for six hours. Further, no loss of cefotaxime activity was detected in any combination. (973)

The inactivation of gentamicin, tobramycin, and amikacin, each 5 g/mL, by seven -lactam antibiotics, 250 and 500 g/mL, in serum at 25 C over 24 hours was studied using bioassay, enzyme-mediated immunoassay technique (EMIT), fluorescence polarization immunoassay (TDx), and radioimmunoassay. No inactivation of any aminoglycosides by the cephalosporins moxalactam, cefotaxime, and cefazolin occurred within the study period. (654)

Spruill et al. evaluated the effect of various cephalosporins on tobramycin sulfate 7.7 g/mL in human serum. At concentrations of 250 and 1000 g/mL, cefazolin, cefoxitin, cefamandole, cefoperazone, and cefotaxime caused about a 10 to 15% loss of tobramycin over 48 hours at 0 and 21 C. Moxalactam caused about a 15% loss at 0 C and a 20 to 30% loss at 21 C over 48 hours. (1005)

Pennell et al. evaluated the potential for inactivation of tobramycin sulfate (Lilly) 9 g/mL with 100- and 200-g/mL concentrations of cefotaxime (Hoechst-Roussel) in human serum. No loss of tobramycin sulfate was determined by TDx fluorescence polarization immunoassay over 48 hours when stored at 4, 24, and 37 C. (1420)

The in vivo activities of amikacin sulfate and gentamicin sulfate administered with cefotaxime sodium were evaluated in volunteers. Microbiological assays found no statistically significant reductions in aminoglycoside blood levels in the aminoglycoside-cefotaxime combinations. (504)

Vancomycin The compatibility or incompatibility of vancomycin hydrochloride mixed with or administered simultaneously with cefotaxime sodium is concentration dependent. (2189) See Y-Site Compatibility above. Vancomycin hydrochloride has a low pH and is variably compatible with drugs having neutral to mildly alkaline pH, including cephalosporins and penicillins. The compatibility may depend on a number of factors, including concentration of each drug, dilution vehicle, actual pH of solutions, and completeness of mixing during administration. Combinations that are compatible when well mixed may result in precipitation if only partially mixed, presumably because of regionally different concentrations and pH values. If attempting to administer vancomycin hydrochloride with cefotaxime sodium, take care to ensure that the specific combination and the concentrations are compatible under the exact administration conditions to be used. An inline filter should be used as a final safety measure. (2189)

References






ISBN: o ISBN-13: 978-1-58528-213-5









"C" Monographs Cefotaxime Sodium - AHFS 8:12.06.12


Ceftazidime - AHFS 8:12.06.12

Products Ceftazidime is supplied in vials containing 500 mg, 1 g, and 2 g of drug (under reduced pressure), infusion packs containing 1 and 2 g of drug, and 6-g pharmacy bulk packages. The dosage forms contain sodium carbonate 118 mg per gram of ceftazidime. The sodium salt of ceftazidime and carbon dioxide are formed during reconstitution. (1-1/07) (1-2/07) (4) The use of a venting needle has been suggested for ease of use. (1136) Spraying or leaking of the solution after needle withdrawal has been reported, especially with smaller vials. (1137) The use of larger vials reduces the occurrence of such leakage. (1137) (1138) Care must be taken if a multiple-additive set with a two-way valve is used for reconstitution. The negative pressure in the Glaxo Wellcome product may cause inaccuracies in the volume of diluent added to the vial. In one test, almost 3 mL extra entered the vial during reconstitution. (1240) Vials have been vented prior to reconstitution, but Glaxo Wellcome recommends clamping the tubing from the supply bottle prior to adding the diluent to the vial when multiple-additive sets are used. (1241)

Ceftazidime is also supplied in frozen solutions containing 1 and 2 g/50 mL of dextrose 4.4 and 3.2%, respectively. (1-2/07) (4)

For intramuscular injection, ceftazidime should be reconstituted with sterile water for injection, bacteriostatic water for injection, or lidocaine hydrochloride 0.5 or 1% using 1.5 mL for the 500-mg vial and 3 mL for the 1-g vial. Any carbon dioxide bubbles that are withdrawn into the syringe should be expelled prior to injection. (1-1/07) (1-2/07) (4)

For direct intravenous injection, ceftazidime should be reconstituted with sterile water for injection. Carbon dioxide will form during dissolution, but the solution will clear in about one to two minutes. (1-1/07) (1-2/07) (4)

For intravenous infusion, the reconstituted solution can be added to a compatible infusion solution (after expelling any carbon dioxide bubbles that have entered the syringe). Alternatively, the 1- or 2-g infusion packs can be reconstituted with 100 mL of compatible infusion solution, yielding a 10- or 20-mg/mL solution, respectively. (1-1/07) (1-2/07) (4) To reconstitute the infusion packs, add the diluent in two increments. Initially, add 10 mL with shaking to dissolve the drug. To release the carbon dioxide pressure, insert a venting needle through the closure only after the drug has dissolved and become clear (about one to two minutes). Then add the remaining 90 mL and remove the venting needle. Additional pressure may develop, especially during storage, and should be released prior to use. (4)

The 6-g pharmacy bulk package should be reconstituted with 26 mL of a compatible diluent to yield 30 mL of solution containing 200 mg/mL of ceftazidime. The carbon dioxide pressure that


develops should be released using a venting needle. The 200-mg/mL concentrated solution must be diluted further for intravenous use. (1-1/07) (1-2/07)

Table 1. Reconstitution for Intravenous Injection 1-1/07 1-2/07

================================================== Product Volume of Withdrawable Concentration Diluent Volume ================================================== 500 mg 5.3 mL 5.7 mL 100 mg/mL -------------------------------------------------- 1 g 10 mL 10.6 mL 100 mg/mL -------------------------------------------------- 2 g 10 mL 11.5 mL 170 mg/mL --------------------------------------------------

pH From 5 to 8. (1-1/07) (1-2/07) (4)

Osmolality The osmolality of ceftazidime (Fortaz, Glaxo) 50 mg/mL was determined to be 321 mOsm/kg in dextrose 5% and 330 mOsm/kg in sodium chloride 0.9%. (1375)

Robinson et al. recommended the following maximum ceftazidime concentrations to achieve osmolalities suitable for peripheral infusion in fluid-restricted patients (1180) :

========================================== Diluent Maximum Osmolality Concentration (mOsm/kg) (mg/mL) ========================================== Dextrose 5% 70 503 ------------------------------------------ Sodium 63 486 chloride 0.9% ------------------------------------------ Sterile water 126 302 for injection ------------------------------------------

Sodium Content Each gram of ceftazidime activity provides 2.3 mEq (54 mg) of sodium from the sodium carbonate present in the formulation. (1-1/07) (1-2/07) (4)

Trade Name(s) Fortaz, Tazicef

Administration Ceftazidime may be administered by deep intramuscular injection, by direct intravenous injection over three to five minutes directly into a vein or through the tubing of a running compatible infusion solution, or by intermittent intravenous infusion over 15 to 30 minutes. The manufacturer recommends temporarily discontinuing other solutions being administered at the same site during ceftazidime infusion. The sodium carbonate-containing formulation may be instilled intraperitoneally in a concentration of 250 mg/2 L of compatible dialysis solution. (1-1/07) (1-2/07) (4)

Stability Intact vials should be stored at controlled room temperature and protected from light. (1-1/07) (1-2/07) Approximately 2% decomposition has been reported after 12 months of storage at 37 C with protection from light. (1136)

Reconstituted ceftazidime solutions are light yellow to amber, depending on the diluent and concentration, and may darken on storage. Color changes do not necessarily indicate a potency loss. (1-1/07) (1-2/07) (4)

Solutions in sterile water for injection at 95 to 280 mg/mL, in lidocaine hydrochloride 0.5 or 1% or bacteriostatic water for injection at 280 mg/mL, and in sodium chloride 0.9% or dextrose 5% at 10 or 20 mg/mL in piggyback infusion packs are stable for 24 hours at room temperature and seven days under refrigeration. Tazicef and Tazidime in sterile water for injection at 95 to 280 mg/mL or in sodium chloride 0.9% at 10 to 20 mg/mL are stable for 24 hours at room temperature and seven days under refrigeration. (1-1/07) (1-2/07)

One report of ceftazidime in concentrations of 1, 40, and 333 mg/mL in water indicated no loss after 24 hours at 4 C and six hours at 25 C. About a 4 to 6% loss was reported after 24 hours at 25 C. (1136)

Ceftazidime vials reconstituted with sterile water for injection to a concentration of 270 mg/mL were evaluated for stability at four temperatures. HPLC and capillary electrophoresis analyses were in good agreement for the samples. About 8 to 9% ceftazidime loss occurred in 7 days under refrigeration at 4 C and in 4 days at 10 C. At 20 C about 7 to 8% loss occurred in 24 hours, but at a higher room temperature of 30 C about 5% loss occurred in six hours and 12% loss occurred in 18 hours. (2285)

Freezing Solutions The various ceftazidime products differ in their reported stabilities, both during frozen storage of their solutions and after thawing. Table 2 summarizes the reported stabilities. (4)

Table 2. Reported Stabilities of Frozen and Thawed Solutions of Ceftazidime Products 1-1/07 1-2/07 4 aIn sterile water for injection.bThawed and stored at room temperature.cThawed and stored at 4 to 5 C.dIn sodium chloride 0.9%.eIn sodium chloride 0.9% and dextrose 5%.fIn infusion packs.

======================================== Concentration Fortaz Tazicef ======================================== 280 mg/mL 3 monthsa 3 monthsa ---------------------------------------- Thawed/RTb 8 hr 8 hr ---------------------------------------- Thawed/4 Cc 4 days 4 days ---------------------------------------- ---------------------------------------- 100 to 180 mg/ 6 monthsad 3 monthse mL ---------------------------------------- Thawed/RT 24 hr 8 hr ---------------------------------------- Thawed/4 C 7 days 4 days ---------------------------------------- ---------------------------------------- 10 to 20 mg/mLf 9 monthsa ---------------------------------------- Thawed/RT 24 hr ---------------------------------------- Thawed/4 C 7 days ----------------------------------------

The commercially available frozen ceftazidime solutions (Fortaz, Glaxo) of 1 and 2 g/50 ml of sodium chloride 0.9%, when thawed, are stable for 24 hours at room temperature or seven days under refrigeration. (4)

Minibags of ceftazidime in dextrose 5% or sodium chloride 0.9%, frozen at -20 C for up to 35 days, were thawed at room temperature and in a microwave oven, with care taken that the

thawed solution temperature never exceeded 25 C. No significant differences in ceftazidime concentrations occurred between the two thawing methods. (1192)

Ceftazidime (Fortaz, Glaxo) 1 g/50 mL in sodium chloride 0.9% was stored frozen at -20 C. HPLC and microbiological analyses found about 7% loss in 97 days. After thawing at room temperature, subsequent storage refrigerated for 4 days and at room temperature for 24 hours resulted in additional loss with only about 90% of the ceftazidime remaining. (500)

Ceftazidime (Tazidime, Lilly) 40 mg/mL in both dextrose 5% and sodium chloride 0.9% exhibited approximately a 4 to 6% loss after storage at -10 C for 90 days. Thawing in a microwave oven did not affect stability. (1341)

Stiles et al. reported less than a 2% ceftazidime (Fortaz, Glaxo) loss from a solution containing 36.6 mg/mL in sterile water for injection in PVC and glass containers after 30 days at -20 C. Subsequent thawing and storage for four days at 5 C, followed by 24 hours at 37 C to simulate the use of a portable infusion pump, resulted in little additional ceftazidime loss. (1391)

Ceftazidime (Fortaz, Glaxo) 100 and 200 mg/mL in sterile water for injection in glass vials and polypropylene syringes (Becton-Dickinson) was stored frozen at -20 C for 91 days followed by eight hours at 22 C. Losses of about 5 and 10% by HPLC occurred in the 100- and 200-mg/mL concentrations, respectively. Freezing at -20 C for 91 days followed by refrigeration at 4 C for four days resulted in losses of about 10 and 6% in the 100- and 200-mg/mL concentrations, respectively. Particle counts remained within USP limits throughout the study. (1580)

Ceftazidime (Fortaz, Glaxo) 20 mg/mL in dextrose 5% and sodium chloride 0.9% frozen at -20 C for 12 weeks exhibited 5% or less loss of potency by HPLC analysis in latex elastomeric reservoirs (Secure Medical) and in glass containers. (1970)

Usually, frozen solutions should be thawed at room temperature or under refrigeration. Other techniques are not recommended. Thawed solutions should not be refrozen. (1-2/07) (4)

Light Effects Ceftazidime reconstituted with sterile water for injection to a concentration of 270 mg/mL exhibited no substantial difference in stability when stored protected from light or exposed to daylight. (2285)

Syringes Ceftazidime (Fortaz, Glaxo) 100 and 200 mg/mL in sterile water for injection in polypropylene syringes (Becton-Dickinson) and glass vials exhibited a 5% or less loss by HPLC in eight hours at 22 C and 96 hours at 4 C. (1580)

Ceftazidime (Fortaz, Glaxo) 100 mg/mL in sterile water for injection, packaged as 0.4 mL in 1-mL Injekt syringes (Braun) sealed with blind hubs and stored at about 6 C, retained antibiotic activity against Pseudomonas aeruginosa for seven days. However, the yellow color of the solution became much darker over this period. (1697)

Ambulatory Pumps Exposure of ceftazidime (Fortaz, Glaxo) 36.6 mg/mL in sterile water for injection to 37 C for 24 hours, to simulate the use of a portable infusion pump, resulted in little or no ceftazidime loss. (1391)

Ceftazidime (Fortaz, Glaxo) at a concentration of 60 mg/mL in water for injection was filled into PVC portable infusion pump reservoirs (Pharmacia Deltec). Storage at -20 C resulted in less than 3% loss in 14 days. The thawed reservoirs were then stored under refrigeration at 6 C. Losses totaled 10% after five days of refrigerated storage. Under simulated use conditions at 30 C, ceftazidime decomposes at a rate of about 10% in 18 hours. The authors concluded prefilling of reservoirs with ceftazidime solutions for home use was not advisable. (2008)

Ceftazidime (Fortaz, Glaxo Wellcome) 40 mg/mL in UltraFlow PVC reservoirs (Fresenius-Kabi) and Outbound polyethylene reservoirs (Zambon) was unstable. Over 10% loss occurred in about 12 hours when diluted in dextrose 5% and in 12 to 16 hours when diluted in sodium chloride 0.9%. Utility periods restricted to about 9 hours in dextrose 5% and 12 hours in sodium chloride 0.9% are appropriate based on these data. (2421)

Elastomeric Reservoir Pumps Ceftazidime (Fortaz, Glaxo) 20 mg/mL in dextrose 5% and sodium chloride 0.9% 100 mL was packaged in latex elastomeric reservoirs (Secure Medical). A 5% loss by HPLC analysis occurred in seven days at 5 C. Stored at 25 C, a 9% loss in dextrose 5% and a 4% loss in sodium chloride 0.9% occurred in 18 hours. (1970)

Ceftazidime (Fortaz, Glaxo) was prepared as a 60-mg/mL solution in sodium chloride 0.9% and packaged in elastomeric ambulatory pumps (Homepump, Block Medical). The solutions were visually compatible and exhibited 9% loss stored at 4 C and no loss at -20 C in 14 days protected from light. However, potentially toxic pyridine 0.53 mg/mL was found in the refrigerated solutions. Frozen solutions had much less pyridine. The authors recommended freezing such solutions if long-term storage is needed. (2113)

Ceftazidime (Fortaz, Glaxo Wellcome) 40 mg/mL in Infusor LV 10 reservoirs (Baxter) and Easypump reservoirs (B. Braun) was unstable. Over 10% loss occurred in about 12 hours when diluted in dextrose 5% and in 16 to 20 hours when diluted in sodium chloride 0.9%. Utility periods restricted to about 10 hours in dextrose 5% and 14 hours in sodium chloride 0.9% are appropriate based on these data. (2421)

Solutions of ceftazidime in elastomeric reservoir pumps have been stated by the pump manufacturers to be stable for the following time periods frozen, refrigerated (REF), or at room temperature (RT) (31) :

========================================================= Pump Conc. Frozen REF RT Reservoir(s) ========================================================= Homepump; 20 mg/mLb 84 days 7 days 18 hr Home- --------------------------------------------------------- pump Eclipse 5 to 40 mg/ 14 days 24 hr mLb --------------------------------------------------------- Intermate 5 to 40 mg/ 7 days 24 hr mLab --------------------------------------------------------- 5 to 60 mg/ 8 weeks mLb --------------------------------------------------------- Medflo 20 mg/mLab 12 weeks 10 days 24 hr --------------------------------------------------------- ReadyMed 20 mg/mLb 4 weeks 14 days 48 hr --------------------------------------------------------- aIn dextrose 5%. bIn sodium chloride 0.9%. ---------------------------------------------------------

Sorption Ceftazidime 4 mg/mL in dextrose 5% and sodium chloride 0.9% exhibited no loss due to sorption to PVC containers over 24 hours and to administration sets during one-hour simulated infusions. (1953)

Ceftazidime (Fortaz, Glaxo Wellcome) 10 mg/mL in dextrose 5% and sodium chloride 0.9% packaged in PVC, polyethylene, and glass containers exhibited little or no loss due to sorption to any of the container types when stored at 4 and 22 C for 24 hours protected from light. (2289)

Central Venous Catheter Ceftazidime (Fortaz, Glaxo Wellcome) 10 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. HPLC analysis was used to evaluate completeness of drug delivery through the catheter and the amount of chlorhexidine removed from the internal lumens. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter. (2335)

Ceftazidime 10 mg/mL with heparin sodium 5000 units/mL as an antibiotic lock in polyurethane central hemodialysis catheters lost about 50% of the antibiotic over 72 hours at 37 C. The loss was attributed to sorption to the catheters. Nevertheless, the reduced antibiotic concentration (about 5 mg/mL) remained effective against common microorganisms in catheter-related bacteremia in hemodialysis patients. (2515) (2516)



Ceftazidime

=========================================================================================== Solution Mfr Mfr Conc/L Remarks Ref C/I =========================================================================================== Amino acids AB GLc 6 g No substantial amino acid 1535 C 5%, degradation in 48 hr at 22 C and dextrose 10 days at 4 C. Ceftazidime 25% stability the determining factor ------------------------------------------------------------------------------------------- Dextrose 5% GLc 20 g 5% loss in 24 hr at 25 C and no 1136 C in sodium loss in 48 hr at 4 C chloride 0.9% ------------------------------------------------------------------------------------------- Dextrose 5% MGa GLc 20 g Physically compatible with 5% drug 1026 C loss in 24 hr and 9% in 48 hr at 25 C under fluorescent light ------------------------------------------------------------------------------------------- Dextrose 5% GLc 20 g 6% loss in 24 hr at 25 C. No loss 1136 C in 24 hr and 3% loss in 48 hr at 4 C ------------------------------------------------------------------------------------------- Dextrose 5% TRa 40 g Physically compatible with 8% loss 1341 C in 2 days at 25 C and 6% loss in 21 days at 5 C ------------------------------------------------------------------------------------------- Dextrose 5% b GLc 40 g Physically compatible with 7% loss 1353 C in 1 day and 19% loss in 3 days at 23 C; 8% loss in 10 days at 4 C ------------------------------------------------------------------------------------------- Dextrose 5% BAb GLc 2 and 6 Visually compatible with 7 to 9% 1937 C g loss by HPLC in 24 hr at room

temperature ------------------------------------------------------------------------------------------- Dextrose 5% b 4 g Visually compatible with little or 1953 C no loss by HPLC in 24 hr at room temperature and 4 C ------------------------------------------------------------------------------------------- Dextrose 5% ABd GLc 20 g 6 to 9% loss by HPLC in 18 hr at 25 1970 C C and in 7 days at 5 C ------------------------------------------------------------------------------------------- Dextrose 5% BAb, GW 10 g Visually compatible with little or 2289 C BRNaj no loss by HPLC in 24 hr at 4 and 22 C ------------------------------------------------------------------------------------------- Dextrose 5% BAl

GW 40 g 10% loss in about 12 hr at 37 C in 2421 I the dark ------------------------------------------------------------------------------------------- Dextrose 5% m GW 40 g Losses of 5, 8, and 10% in 20 hr at 2539 C 20 C, and losses of 9, 17, and 21% in 20 hr at 35 C in glass, polypropylene, and PVC containers, respectively ------------------------------------------------------------------------------------------- Ringer's GLc 20 g 6% loss in 24 hr at 25 C and 1% 1136 C injection, loss in 48 hr at 4 C lactated ------------------------------------------------------------------------------------------- Sodium GLc 20 g 3% loss in 6 hr and 11% in 24 hr at 1136 C bicarbonate 25 C. 1% loss in 24 hr and 3% in 4.2% 48 hr at 4 C ------------------------------------------------------------------------------------------- Sodium MGa GLc 20 g Physically compatible with 2% drug 1026 C chloride loss in 24 hr and 5% in 48 hr at 0.9% 25 C under fluorescent light ------------------------------------------------------------------------------------------- Sodium GLc 20 g 7% loss in 24 hr at 25 C and no 1136 C chloride loss in 48 hr at 4 C 0.9% ------------------------------------------------------------------------------------------- Sodium TRa 40 g Physically compatible with 5% loss 1341 C chloride in 2 days and 12% loss in 3 days 0.9% at 25 C; 7% loss in 28 days at 5 C ------------------------------------------------------------------------------------------- Sodium b GLc 40 g Physically compatible with 3% loss 1353 C chloride in 1 day and 14% loss in 3 days 0.9% at 25 C; 10% loss in 14 days at 5 C ------------------------------------------------------------------------------------------- Sodium BAe GLf 60 g 9% loss by HPLC in 24 hr stored at 1860 C chloride 27 C 0.9% ------------------------------------------------------------------------------------------- Sodium BAe GLf 60 g Stored for up to 144 hr at 4 C 1860 C chloride followed by 27 C; 9% loss by 0.9% HPLC in 20 hr at 27 C ------------------------------------------------------------------------------------------- Sodium BAe GLf 120 g 9% loss by HPLC in 16 hr stored at 1860 C chloride 27 C 0.9% ------------------------------------------------------------------------------------------- Sodium BAe GLf 120 g Stored for up to 144 hr at 4 C 1860 C chloride followed by 27 C; 9 to 11% loss 0.9% by HPLC in 16 hr at 27 C ------------------------------------------------------------------------------------------- Sodium BAb GLc 2 and 6 Visually compatible with 4 to 6% 1937 C chloride g loss by HPLC in 24 hr at room 0.9% temperature ------------------------------------------------------------------------------------------- Sodium b 4 g Visually compatible with little or 1953 C chloride no loss by HPLC in 24 hr at room 0.9% temperature and 4 C ------------------------------------------------------------------------------------------- Sodium ABd GLc 20 g 3 to 5% loss of drug by HPLC in 18 1970 C chloride hr at 25 C and 7 days at 5 C 0.9% ------------------------------------------------------------------------------------------- Sodium KAh GLc 60 g Visually compatible with little or 2113 C chloride no loss of ceftazidime by HPLC 0.9% and little formation of pyridine in 14 days frozen at -20 C protected from light ------------------------------------------------------------------------------------------- Sodium KAh GLc 60 g Visually compatible with 9% loss of 2113 ? chloride ceftazidime by HPLC but formation 0.9%

of potentially toxic pyridine 0.53 mg/mL in 14 days at 4 C protected from light ------------------------------------------------------------------------------------------- Sodium BAi GWf 24 g Losses of 0 to 4% by HPLC in 24 hr 2273 ? chloride in samples cooled by ice packs. 0.9% One sample exhibited 18% loss ------------------------------------------------------------------------------------------- Sodium BAb, GW 10 g Visually compatible with little or 2289 C chloride BRNaj no loss by HPLC in 24 hr at 4 and 0.9% 22 C ------------------------------------------------------------------------------------------- Sodium BAk GSKc 20 g Physically compatible with no 2370 C chloride increase in measured haze or 0.9% particle content. About 4% loss in 24 hr and 15% loss in 3 days at 23 C and about 2% loss in 7 days and 15% loss in 14 days at 4 C protected from light ------------------------------------------------------------------------------------------- Sodium BAl GW 40 g 10% loss occurred in about 12 to 16 2421 I chloride hr at 37 C in the dark 0.9% ------------------------------------------------------------------------------------------- Sodium m GW 40 g Losses of 1, 3, and 6% in 20 hr at 2539 C chloride 20 C, and losses of 6, 11, and 0.9% 13% in 20 hr at 35 C in glass, polypropylene, and PVC containers, respectively ------------------------------------------------------------------------------------------- TPN #107g 1 g Ceftazidime activity retained for 1326 C 24 hr at 21 C by microbiological assay ------------------------------------------------------------------------------------------- TPN #141 to GLc 1 g Visually compatible with 8% 1535 C #143g ceftazidime loss in 6 hr and 10% loss in 24 hr by HPLC at 22 C. 8% ceftazidime loss in 3 days at 4 C ------------------------------------------------------------------------------------------- TPN #141 to GLc 6 g Visually compatible with 6% 1535 C #143g ceftazidime loss in 12 hr and 11 to 13% loss in 24 hr by HPLC at 22 C. 7 to 9% ceftazidime loss in 3 days at 4 C ------------------------------------------------------------------------------------------- aTested in glass containers. bTested in PVC containers. cSodium carbonate-containing formulation. dTested in glass containers and latex elastomeric reservoirs (Secure Medical). eTested in Singleday Infusors (Baxter). fArginine-containing formulation. gRefer to Appendix I for the composition of parenteral nutrition solutions. TPN indicates a 2- in-1 admixture. hTested in elastomeric ambulatory pumps (Homepump, Block Medical). iTested in Homepump (Block Medical) elastomeric infusion devices. jTested in polyethylene plastic containers. kTested in ethylene vinyl acetate (EVA) plastic AutoDose bags (Tandem Medical). lTested in Infusor LV 10 (elastomeric), Easypump LT 125 (elastomeric), Ultra-Flow (PVC), and Outbound (polyethylene) infusion device reservoirs. mTested in glass, polypropylene, and PVC containers.


Ceftazidime

============================================================================================================== Drug Mfr Conc/L Mfr Conc/L Test Soln Remarks Ref C/I ============================================================================================================== Amikacin BR 25 mg GLa 50 mg D5W About 28% loss of amikacin in 2 hr 504 I sulfate at 22 C by microbiological assay BR 25 mg GLa 50 mg D5W About 17% loss of amikacin in 24 hr 504 I at 22 C by microbiological assay -------------------------------------------------------------------------------------------------------------- Aminophylline ES 1 g GLa 2 g D5W, NS 20 to 23% ceftazidime loss by HPLC 1937 I in 6 hr at

room temperature ES 1 g GLa 6 g D5W, NS 8 to 10% ceftazidime loss and 13% 1937 I theophylline loss by HPLC in 6 hr at room temperature ES 2 g GLa 2 g D5W, NS 35 to 40% ceftazidime loss by HPLC 1937 I in 6 hr at room temperature ES 2 g GLa 6 g D5W, NS 22% ceftazidime loss by HPLC in 6 1937 I hr at room temperature -------------------------------------------------------------------------------------------------------------- Ciprofloxacin MI 2 g 20 g D5W Physically incompatible 888 I BAY 2 g SKBa 19.8 g D5W Visually compatible but pH changed 2413 ? by more than 1 unit -------------------------------------------------------------------------------------------------------------- Clindamycin UP 9 g GLa 20 g D5Wb Physically compatible with 9% 1026 C phosphate clindamycin loss and 11% ceftazidime loss in 48 hr at 25 C under fluorescent light UP 9 g GLa 20 g NSb Physically compatible with 5% 1026 C clindamycin loss and 7% ceftazidime loss in 48 hr at 25 C under fluorescent light -------------------------------------------------------------------------------------------------------------- Floxacillin GSK 40 g GSK 40 g NS, W Physically compatible with less 2658 C sodium than 10% drug loss by HPLC in 24 hr at room temperature and 4 C GSK 120 g GSK 60 g NS, W Physically compatible with less 2658 C than 10% drug loss by HPLC in 24 hr at room temperature and 4 C GSK 240 g GSK 180 g NS, W Physically compatible with less 2658 C than 10% drug loss by HPLC in 24 hr at room temperature and 4 C -------------------------------------------------------------------------------------------------------------- Fluconazole PF 1 g GL 20 g D5W Visually compatible with no 1677 C fluconazole loss by HPLC in 72 hr at 25 C under fluorescent light. Ceftazidime not tested -------------------------------------------------------------------------------------------------------------- Gentamicin SC 6 and 9 GLa 50 mg D5W 10 to 20% loss of gentamicin in 2 504 I sulfate mg hr at 22 C by microbiological assay -------------------------------------------------------------------------------------------------------------- Linezolid PHU 2 g GWa 20 g c Physically compatible with no 2262 C linezolid loss by HPLC in 7 days at 4 and 23 C protected from light. Ceftazidime losses of 5% in 24 hr and 12% in 3 days at 23 C and about 3% in 7 days at 4 C -------------------------------------------------------------------------------------------------------------- Metronidazole 5 g GLa 20 g No loss of either drug in 4 hr 1345 C AB 5 g LIa 10 g Visually compatible with little or 1849 C no loss of either drug by HPLC in 72 hr at 8 C -------------------------------------------------------------------------------------------------------------- Ofloxacin HO 1.67 g GLa 8.3 g W Visually compatible with little or 1613 C no loss of either drug by HPLC in 48 hr -------------------------------------------------------------------------------------------------------------- Ranitidine HCl GL 500 mg GLa 10 g D2.5(1/2)S 8% ranitidine loss in 4 hr and 37% 1632 I loss in 24 hr by HPLC at 22 C -------------------------------------------------------------------------------------------------------------- Tenoxicam RC 200 mg LIa 5 g D5Wd Visually compatible for up to 72 hr 2557 C with yellow discoloration. 10% loss of ceftazidime in 96 hr and of tenoxicam in 168 hr at 4 and 25 C RC 200 mg LIa 5 g D5Wb Visually compatible with about 10% 2557 C loss of both drugs in 168 hr at 4 and 25 C -------------------------------------------------------------------------------------------------------------- aSodium carbonate-containing formulation tested. bTested in glass containers. cAdmixed in the linezolid infusion container. dTested in PVC bags.


Ceftazidime

===================================================================================== Drug (in Mfr Amt Mfr Amt Remarks Ref C/I syringe) ===================================================================================== Dimenhydrinate 10 mg/1 a 100 mg/1 Clear solution 2569 C mL mL ------------------------------------------------------------------------------------- Hydromorphone KN 2, 10, GLa 180 mg/1 Visually compatible 2082 C HCl 40 mg/ mL with less than 10% 1 mL loss of either drug by HPLC in 24 hr at room temperature ------------------------------------------------------------------------------------- Pantoprazole 4 mg/1 a 100 mg/1 Precipitates 2574 I sodium mL mL immediately ------------------------------------------------------------------------------------- aSodium carbonate-containing formulation tested.


Ceftazidime

=========================================================================================================== Drug Mfr Conc Mfr Conc Remarks Ref C/I =========================================================================================================== Acetylcysteine 100 mg/mL GSKc 120 mg/ More than 10% ceftazidime loss 2513 I mLk occurs in 1 hr ----------------------------------------------------------------------------------------------------------- Acyclovir sodium BW 5 mg/mLa SKFc 20 mg/mLa Physically compatible for 4 hr 1157 C at 25 C ----------------------------------------------------------------------------------------------------------- Allopurinol sodium BW 3 mg/mLb LIc 40 mg/mLa Physically compatible with no 1686 C change in measured turbidity or increase in particle content in 4 hr at 22 C ----------------------------------------------------------------------------------------------------------- Amifostine USB 10 mg/mLa LIc 40 mg/mLa Physically compatible with no 1845 C change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------- Amikacin sulfate 1.5 mg/mL SKBc 125 mg/mL Visually compatible with less 2434 C than 10% loss of both drugs in 1 hr 15 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Amikacin not tested ----------------------------------------------------------------------------------------------------------- Aminophylline ES 2 mg/mLa GLc 40 mg/mLa Visually compatible with 4% 1937 C ceftazidime loss and 9% theophylline loss by HPLC in 2 hr at room temperature ES 2 mg/mLa GLc 40 mg/mLb Visually compatible with 5% 1937 C ceftazidime loss and 4% theophylline loss by HPLC in 2 hr at room temperature ES 2 mg/mLa GLd 40 mg/mL Visually compatible with no 1937 C ceftazidime or theophylline loss by HPLC in 2 hr at room temperature ES 2 mg/mLa GLe 40 mg/mLa Visually compatible with 5% 1937 C ceftazidime loss and 7% theophylline loss by HPLC in 2 hr at room temperature ES 2 mg/mLa GLe 40 mg/mLb Visually compatible with 2% 1937 C ceftazidime loss and no theophylline loss by HPLC in 2 hr at room temperature

----------------------------------------------------------------------------------------------------------- Amiodarone HCl WY 6 mg/mLa GWc 40 mg/mLa Immediate opaque white turbidity 2352 I ----------------------------------------------------------------------------------------------------------- Amphotericin B SEQ 0.83 mg/ SKBc 40 mg/mLa Increased turbidity forms in 4 2117 I cholesteryl mLa hr at 23 C under fluorescent sulfate complex light SEQ 0.83 mg/ GWe 40 mg/mLa Gross precipitate forms 2117 I mLa ----------------------------------------------------------------------------------------------------------- Amsacrine NCI 1 mg/mLa GLc 40 mg/mLa Light flocculent orange 1381 I precipitate forms immediately, becoming heavier with time ----------------------------------------------------------------------------------------------------------- Anidulafungin VIC 0.5 mg/mLa GSKc 40 mg/mLa Physically compatible with no 2617 C change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------- Azithromycin PF 2 mg/mLb GWc 80 mg/ Amber and white microcrystals 2368 I mLlm found upon filter inspection ----------------------------------------------------------------------------------------------------------- Aztreonam SQ 40 mg/mLa LIc 40 mg/mLa Physically compatible with no 1758 C subvisual haze or particle formation in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------- Bivalirudin TMC 5 mg/mLa GWc 40 mg/mLa Physically compatible with no 2373 C increase in measured haze or particle content in 4 hr at 23 C under fluorescent light ----------------------------------------------------------------------------------------------------------- Ciprofloxacin MI 1 mg/mLa SKFc 20 mg/mLf Physically compatible for 24 hr 1189 C at 22 C ----------------------------------------------------------------------------------------------------------- Cisatracurium GW 0.1 and 2 SKBc 40 mg/mLa Physically compatible with no 2074 C besylate mg/mLa change in measured turbidity or increase in particle content in 4 hr at 23 C GW 5 mg/mLa SKBc 40 mg/mLa Subvisual haze forms immediately 2074 I GW 0.1, 2, 5 GWe 40 mg/mLa Physically compatible with no 2074 C mg/mLa change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------- Clarithromycin 50 mg/mL SKBc 125 mg/mL Immediate precipitation 2434 I 10 mg/mL SKBc 125 mg/mL Trace precipitation 2434 I 50 mg/mL GSKc 120 mg/ Precipitates 2513 I mLk ----------------------------------------------------------------------------------------------------------- Daptomycin CUB 16.7 mg/ GSKc 16.7 mg/ Physically compatible with no 2553 C mLbn mLbc loss by HPLC of either drug in 2 hr at 25 C ----------------------------------------------------------------------------------------------------------- Dexmedetomidine HCl AB 4 g/mLb GWc 40 mg/mLb Physically compatible with no 2383 C increase in measured haze or particle content in 4 hr at 23 C under fluorescent light ----------------------------------------------------------------------------------------------------------- Diltiazem HCl MMD 5 mg/mL GLc 10 and Visually compatible 1807 C 170 mg/ mLb MMD 1 mg/mLb GLc 170 mg/ Visually compatible 1807 C mLb ----------------------------------------------------------------------------------------------------------- Dobutamine HCl 1 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Dobutamine not tested 250 mg/mL GSKc 120 mg/ Precipitates 2513 I mLk ----------------------------------------------------------------------------------------------------------- Docetaxel RPR 0.9 mg/mLa SKBc 40 mg/mLa Physically compatible with no 2224 C change in

measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------- Dopamine HCl 0.4 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Dopamine not tested ----------------------------------------------------------------------------------------------------------- Doxapram HCl RB 2 mg/mLa GWc 40 mg/mLa Visually compatible for 4 hr at 2470 C 23 C ----------------------------------------------------------------------------------------------------------- Doxorubicin HCl SEQ 0.4 mg/mLa SKBc 40 mg/mLa Partial loss of measured natural 2087 I liposome injection turbidity ----------------------------------------------------------------------------------------------------------- Drotrecogin alfa LI 0.1 and 1 GWc 100 mg/ Physically compatible but the pH 2615 ? (activated) mg/mLb mLb was outside the optimal range of drotrecogin alfa (activated) ----------------------------------------------------------------------------------------------------------- Enalaprilat MSD 0.05 mg/ GLc 10 mg/mLa Physically compatible for 24 hr 1355 C mLb at room temperature under fluorescent light ----------------------------------------------------------------------------------------------------------- Epinephrine HCl 50 mcg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Epinephrine not tested ----------------------------------------------------------------------------------------------------------- Erythromycin 50 mg/mL SKBc 125 mg/mL Immediate precipitation 2434 I lactobionate 10 mg/mL SKBc 125 mg/mL Trace precipitation 2434 I 5 mg/mL GSKc 120 mg/ Precipitates 2513 I mLk ----------------------------------------------------------------------------------------------------------- Esmolol HCl DCC 10 mg/mLa GLc 10 mg/mLa Physically compatible for 24 hr 1169 C at 22 C ----------------------------------------------------------------------------------------------------------- Etoposide phosphate BR 5 mg/mLa SKBc 40 mg/mLa Physically compatible with no 2218 C change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------- Famotidine MSD 0.2 mg/mLa GLc 20 mg/mLb Physically compatible for 14 hr 1196 C ME 2 mg/mLb c 20 mg/mLa Visually compatible for 4 hr at 1936 C 22 C ----------------------------------------------------------------------------------------------------------- Fenoldopam mesylate AB 80 g/mLb GWc 40 mg/mLb Physically compatible with no 2467 C increase in measured haze or particle content in 4 hr at 23 C under fluorescent light ----------------------------------------------------------------------------------------------------------- Filgrastim AMG 30 g/mLa LIc 40 mg/mLa Physically compatible with no 1687 C change in measured turbidity or increase in particle content in 4 hr at 22 C AMG 10g and LIc 10 mg/mLa Visually compatible with little 2060 C 40a g/ or no loss of filgrastim mL activity by bioassay and ceftazidime by HPLC in 4 hr at 25 C ----------------------------------------------------------------------------------------------------------- Fluconazole RR 2 mg/mL GL 20 mg/mL Immediate precipitation 1407 I 2 mg/mL SKBc 125 mg/mL Visually compatible with less 2434 C than 10% loss of ceftazidime in 30 min. Fluconazole not tested 2 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Fluconazole not tested ----------------------------------------------------------------------------------------------------------- Fludarabine BX 1 mg/mLa GLc 40 mg/mLa Physically compatible for 4 hr 1439 C phosphate at room temperature under fluorescent light -----------------------------------------------------------------------------------------------------------

Foscarnet sodium AST 24 mg/mL GL 20 mg/mL Physically compatible for 24 hr 1335 C at room temperature under fluorescent light AST 24 mg/mL GL 20 mg/mLf Physically compatible for 24 hr 1393 C at 25 C under fluorescent light by visual and microscopic examination ----------------------------------------------------------------------------------------------------------- Furosemide 10 mg/mL SKBc 125 mg/mL Visually compatible with less 2434 C than 10% loss of ceftazidime in 30 min. Furosemide not tested 10 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Furosemide not tested ----------------------------------------------------------------------------------------------------------- Gallium nitrate FUJ 1 mg/mLb LIc 100 mg/ Visually compatible for 24 hr at 1673 C mLb 25 C ----------------------------------------------------------------------------------------------------------- Gemcitabine HCl LI 10 mg/mLb SKBc 40 mg/mLb Physically compatible with no 2226 C change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------- Gentamicin sulfate 0.6 mg/mL SKBc 125 mg/mL Visually compatible with less 2434 C than 10% loss of both drugs in 1 hr 6 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Gentamicin not tested ----------------------------------------------------------------------------------------------------------- Granisetron HCl SKB 1 mg/mL SKBc 16.7 mg/ Physically compatible with 1883 C mLb little or no loss of either drug by HPLC in 4 hr at 22 C ----------------------------------------------------------------------------------------------------------- Heparin sodium TR 50 units/ LIc 20 mg/mL Visually compatible for 4 hr at 1793 C mL 25 C ----------------------------------------------------------------------------------------------------------- Hetastarch in AB 6% GWc 40 mg/mLa Physically compatible with no 2339 C lactated change in measured turbidity electrolyte or increase in particle injection content in 4 hr at 23 C (Hextend) ----------------------------------------------------------------------------------------------------------- Hydromorphone HCl KN 2, 10, 40 GLc 40a and Visually compatible and potency 1532 C mg/mL 180 mg/ of both drugs by HPLC retained mL for 24 hr ----------------------------------------------------------------------------------------------------------- Idarubicin HCl AD 1 mg/mLb LIc 20 mg/mLa Haze forms in 1 hr 1525 I ----------------------------------------------------------------------------------------------------------- Insulin, regular 100 units/ GSKc 120 mg/ Physically compatible with less 2513 C mL mLk than 10% ceftazidime loss. Insulin not tested ----------------------------------------------------------------------------------------------------------- Isosorbide dinitrate 0.2 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Isosorbide not tested ----------------------------------------------------------------------------------------------------------- Ketamine HCl 10 mg/mL SKBc 125 mg/mL Visually compatible with less 2434 C than 10% loss of ceftazidime in 24 hr. Ketamine not tested 10 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Ketamine not tested ----------------------------------------------------------------------------------------------------------- Labetalol HCl SC 1 mg/mLa GLc 10 mg/mLa Physically compatible for 24 hr 1171 C at 18 C ----------------------------------------------------------------------------------------------------------- Linezolid PHU 2 mg/mL SKBc 40 mg/mLa Physically compatible with no 2264 C change in measured turbidity or increase in particle content in 4 hr at 23 C PHU 2 mg/mL GWe 40 mg/mLa

Physically compatible with no 2264 C change in measured turbidity or increase in particle content in 4 hr at 23 C

----------------------------------------------------------------------------------------------------------- Melphalan HCl BW 0.1 mg/mLb LIc 40 mg/mLb Physically compatible with no 1557 C change in measured turbidity or increase in particle content in 3 hr at 22 C ----------------------------------------------------------------------------------------------------------- Meperidine HCl AB 10 mg/mL LIc 20 and 40 Physically compatible for 4 hr 1397 C mg/mLa at 25 C ----------------------------------------------------------------------------------------------------------- Methylprednisolone 50 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C sodium succinate mLk than 10% ceftazidime loss. Methylprednisolone not tested ----------------------------------------------------------------------------------------------------------- Midazolam HCl RC 1 mg/mLa LIc 20 mg/mLa Haze forms in 1 hr 1847 I 5 mg/mL SKBc 125 mg/mL Immediate precipitation 2434 I 5 mg/mL GSKc 120 mg/ Precipitates 2513 I mLk ----------------------------------------------------------------------------------------------------------- Milrinone lactate SS 0.2 mg/mLa GWc 100 mg/ Visually compatible for 4 hr at 2381 C mLa 25 C ----------------------------------------------------------------------------------------------------------- Morphine sulfate AB 1 mg/mL LIc 20 and 40 Physically compatible for 4 hr 1397 C mg/mLa at 25 C 1 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Morphine not tested ----------------------------------------------------------------------------------------------------------- Nicardipine HCl DCC 0.1 mg/mLa GLc 10 mg/mLa Visually compatible for 24 hr at 235 C room temperature 1 mg/mL SKBc 125 mg/mL Immediate precipitation 2434 I 1 mg/mL GSKc 120 mg/ Precipitates 2513 I mLk ----------------------------------------------------------------------------------------------------------- Ondansetron HCl GL 1 mg/mLb GLc 40 mg/mLa Physically compatible for 4 hr 1365 C at 22 C GL 16 to 160 100 to Physically compatible when 1366 C g/mL 200 mg/ ceftazidime given as 5-min mL bolus via Y-site GL 1 mg/mLb GLe 40 mg/mLa Physically compatible for 4 hr 1365 C at 22 C GL 0.03 and LIc 40 mg/mLa Visually compatible with less 1732 C 0.3 mg/ than 10% loss of either drug mLa by HPLC in 4 hr at 25 C ----------------------------------------------------------------------------------------------------------- Paclitaxel NCI 1.2 mg/mLa LIc 40 mg/mLa Physically compatible with no 1556 C change in measured turbidity in 4 hr at 22 C ----------------------------------------------------------------------------------------------------------- Pemetrexed disodium LI 20 mg/mLb GWc 40 mg/mLa Color darkening and brownish 2564 I discoloration occurs over 4 hr ----------------------------------------------------------------------------------------------------------- Pentamidine FUJ 3 mg/mLa LIc 20 mg/mLa Fine precipitate, difficult to 1880 I isethionate see, forms immediately ----------------------------------------------------------------------------------------------------------- Phenytoin sodium 50 mg/mL GSKc 120 mg/ Precipitates 2513 I mLk ----------------------------------------------------------------------------------------------------------- Propofol ZEN 10 mg/mL SKBc 40 mg/mLa Physically compatible for 1 hr 2066 C at 23 C with no increase in particle content 1 mg/mL SKBc 125 mg/mL Physically incompatible 2434 I 1 mg/mL GSKc 120 mg/ Precipitates 2513 I mLk ----------------------------------------------------------------------------------------------------------- Ranitidine HCl GL 1 mg/mLb GLc 20 mg/mLa 8% ranitidine loss and no 1632 C ceftazidime loss by HPLC in 4 hr at 22 C -----------------------------------------------------------------------------------------------------------

Remifentanil HCl GW 0.025 and GWe 40 mg/mLa Physically compatible with no 2075 C 0.25 mg/ change in measured turbidity mLb or increase in particle content in 4 hr at 23 C 0.2 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Remifentanil not tested ----------------------------------------------------------------------------------------------------------- Sargramostim IMM 10 g/mLb GLc 40 mg/mLb Particles and filaments form in 1436 I 4 hr IMM 6h and 15 LIc 40 mg/mLf Visually compatible for 2 hr 1618 C g/mLb ----------------------------------------------------------------------------------------------------------- Sufentanil citrate 50 g/mL SKBc 125 mg/mL Visually compatible with less 2434 C than 10% loss of ceftazidime in 24 hr. Sufentanil not tested 5 mcg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Sufentanil not tested ----------------------------------------------------------------------------------------------------------- Tacrolimus FUJ 1 mg/mLb GLc 20 mg/mLa Visually compatible for 24 hr at 1630 C 25 C FUJ 10 and 40 GWc 40 mg/mLa Visually compatible with no loss 2216 C g/mLa of either drug by HPLC in 4 hr at 24 C under fluorescent light FUJ 10 and 40 GWc 200 mg/ Visually compatible with no loss 2216 C g/mLa mLa of either drug by HPLC in 4 hr at 24 C under fluorescent light ----------------------------------------------------------------------------------------------------------- Teniposide BR 0.1 mg/mLa LIc 40 mg/mLa Physically compatible with no 1725 C subvisual haze or particle formation in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------- Theophylline TR 4 mg/mL LIc 20 mg/mL Visually compatible for 6 hr at 1793 C 25 C 20 mg/mL GSKc 120 mg/ More than 25% ceftazidime loss 2513 I mLk occurs in 1 hr ----------------------------------------------------------------------------------------------------------- Thiotepa IMMi 1 mg/mLa LIc 40 mg/mLa Physically compatible with no 1861 C change in measured turbidity or increase in particle content in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------- Tigecycline WY 1 mg/mLb 40 mg/mLb Physically compatible for 4 hr 2714 C ----------------------------------------------------------------------------------------------------------- TNA #218 to #226j SKBc 40 mg/mLa Visually compatible with no 2215 C precipitate or emulsion damage apparent in 4 hr at 23 C GLe 40 mg/mLa Visually compatible with no 2215 C precipitate or emulsion damage apparent in 4 hr at 23 C ----------------------------------------------------------------------------------------------------------- Tobramycin sulfate 0.6 mg/mL SKBc 125 mg/mL Visually compatible with less 2434 C than 10% loss of both drugs in 1 hr 6 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Tobramycin not tested ----------------------------------------------------------------------------------------------------------- TPN #141 to #143j GLc 40 mg/mLf Visually compatible with 4% or 1535 C less ceftazidime loss in 2 hr at 22 C in 1:1 and 1:3 ratios ----------------------------------------------------------------------------------------------------------- TPN #189j GLc 200 mg/ Visually compatible for 24 hr at 1767 C mLk 22 C ----------------------------------------------------------------------------------------------------------- TPN #203 and TPN LIc 60 mg/mL Visually compatible for 2 hr at 1974 C #204j 23 C ----------------------------------------------------------------------------------------------------------- TPN #212 to #215j SKBc 40 mg/mLa Physically compatible with no 2109 C change in measured turbidity or increase in particle content in 4 hr at 23 C -----------------------------------------------------------------------------------------------------------

Uradipil HCl 0.5 mg/mL SKBc 125 mg/mL Visually compatible with less 2434 C than 10% loss of both drugs in 1 hr 5 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Uradipil not tested ----------------------------------------------------------------------------------------------------------- Valproate sodium 100 mg/mL SKBc 125 mg/mL Visually compatible with less 2434 C than 10% loss of ceftazidime in 24 hr. Valproate sodium not tested 100 mg/mL GSKc 120 mg/ Physically compatible with less 2513 C mLk than 10% ceftazidime loss. Valproate sodium not tested ----------------------------------------------------------------------------------------------------------- Vancomycin HCl AB 20 mg/mLa SKBc 10a, 50a, Gross white precipitate forms 2189 I 200k immediately mg/mL AB 20 mg/mLa SKBc 1 mg/mLa Physically compatible with no 2189 C change in measured turbidity or increase in particle content in 4 hr at 23 C AB 2 mg/mLa SKBc 1a, 10a, Physically compatible with no 2189 C 50a, change in measured turbidity 200k or increase in particle mg/mL content in 4 hr at 23 C 30 mg/mL SKBc 125 mg/mL Immediate precipitation 2434 I 30 mg/mL GSKc 120 mg/ Precipitates 2513 I mLk ----------------------------------------------------------------------------------------------------------- Vinorelbine tartrate BW 1 mg/mLb LIc 40 mg/mLb Physically compatible with no 1558 C change in measured turbidity or increase in particle content in 4 hr at 22 C ----------------------------------------------------------------------------------------------------------- Warfarin sodium DME 2 mg/mLk SKBc 20 mg/mLa Haze forms in 24 hr at 24 C 2078 I ----------------------------------------------------------------------------------------------------------- Zidovudine BW 4 mg/mLa GLc 20 mg/mLa Physically compatible for 4 hr 1193 C at 25 C under fluorescent light by visual and microscopic examination ----------------------------------------------------------------------------------------------------------- aTested in dextrose 5%. bTested in sodium chloride 0.9%. cSodium carbonate-containing formulation tested. dTested in the ceftazidime premixed infusion. eArginine formulation tested. fTested in both dextrose 5% and sodium chloride 0.9%. gTested in dextrose 5% with human albumin 2 mg/mL. hWith human albumin 0.1%. iLyophilized formulation tested. jRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3- in-1 admixture, and TPN indicates a 2-in-1 admixture. kTested in sterile water for injection. lTested in sodium chloride 0.45%. mInjected via Y-site into an administration set running azithromycin. nFinal concentration after mixing.


Infusion Solutions Ceftazidime, at the concentrations and in the infusion solutions noted in Table 3, is stated to be physically compatible and chemically stable for 24 hours at room temperature and for seven days under refrigeration. (1-1/07) (1-2/07) (4)

Table 3. Infusion Solutions and Concentrations for Ceftazidime Dilution

======================================= Concentration (mg/mL) Infusion Fortaz Tazicef Solution ======================================= Dextrose 5% 1 to 40 1 to 40 in sodium chloride 0.2, 0.45, or 0.9% --------------------------------------- Dextrose 5% 1 to 40 1 to 40 --------------------------------------- Dextrose 10% 1 to 40 1 to 40 --------------------------------------- Invert sugar 1 to 20 10% --------------------------------------- Normosol M in 1 to 20 dextrose 5% --------------------------------------- Ringer's 1 to 20 1 to 40 injection --------------------------------------- Ringer's 1 to 20 1 to 40 injection, lactated

--------------------------------------- Sodium 1 to 40 1 to 40 chloride 0.9% --------------------------------------- Sodium 1 to 40 lactate (1/ 6) M ---------------------------------------

Infusions in sodium chloride 0.9% or dextrose 5% are stated to be stable for six hours at room temperature in plastic tubing, drip chambers, and volume-control devices of administration sets. (1-1/07) (1-2/07) (4)

The drug is stated to be less stable in sodium bicarbonate injection, and its use as a diluent is not recommended. (1-1/07) (1-2/07) (4)

Peritoneal Dialysis Solutions Ceftazidime 2 mg/mL in Dianeal with dextrose 1.5% is stated to be stable for 10 days under refrigeration, 24 hours at room temperature, and at least four hours at 37 C. (4)

Ceftazidime (Fortaz, Glaxo) 125 mg/L and tobramycin sulfate (Lilly) 8 mg/L in Dianeal PD-2 with dextrose 2.5% (Baxter) were visually compatible and chemically stable by HPLC (ceftazidime) and fluorescence polarization immunoassay (tobramycin). After 16 hours of storage at 25 C under fluorescent light, the loss of both drugs was less than 3%. Additional storage for eight hours at 37 C, to simulate the maximum peritoneal dwell time, showed tobramycin sulfate concentrations of 96% and ceftazidime concentrations of 92 to 96%. (1652)

Ceftazidime (Fortaz, Glaxo) 0.1 mg/mL in Dianeal PD-2 with dextrose 1.5% in PVC containers was physically and chemically stable by HPLC analysis for 24 hours at 25 C exposed to light, exhibiting about 9% loss; additional storage for eight hours at 37 C resulted in additional loss of about 6%. Under refrigeration at 4 C protected from light, no loss occurred in seven days. Additional storage for 16 hours at 25 C followed by eight hours at 37 C resulted in about 6% loss. (1989)

Ceftazidime (Fortaz, Glaxo) 0.1 mg/mL admixed with teicoplanin (Marion Merrell Dow) 0.025 mg/mL in Dianeal PD-2 with dextrose 1.5% in PVC containers did not result in a stable mixture. Using HPLC analysis, large (but variable) teicoplanin losses generally in the 20% range were noted in as little as two hours at 25 C exposed to light. Ceftazidime losses of about 9% occurred in 16 hours. Refrigeration and protection from light of the peritoneal dialysis admixture reduced losses of both drugs to negligible levels. Even so, the authors did not recommend admixing these two drugs because of the high levels of teicoplanin loss at room temperature. (1989)

Ceftazidime (Fortaz, Glaxo) 0.1 mg/mL in Dianeal PD-2 with dextrose 1.5% with or without heparin sodium 1 unit/mL in PVC bags was chemically stable by HPLC analysis for up to six days at 4 C (about 3 to 4% loss), four days at 25 C (about 9 to 10% loss), and less than 12 hours at body temperature of 37 C. (866)

The addition of vancomycin hydrochloride (Lederle) 0.05 mg/mL to this peritoneal dialysis solution demonstrated similar stability with the ceftazidime being the defining component. Ceftazidime was chemically stable by HPLC analysis for up to six days at 4 C (about 3% loss), three days at 25 C (about 9 to 10% loss), and 12 hours at body temperature of 37 C with the vancomycin exhibiting less loss throughout. (866)

Vancomycin hydrochloride (Lilly) 1 mg/mL admixed with ceftazidime (Tazidime, Lilly) 0.5 mg/mL in Dianeal PD-2 (Baxter) with 1.5% and also 4.25% dextrose were evaluated for compatibility and stability. Samples were stored under fluorescent light at 4 and 24 C for 24 hours and at 37 C for 12 hours. No precipitation or other change was observed by visual inspection in any sample. HPLC analysis found no loss of either drug in the samples stored at 4 C and no loss of vancomycin hydrochloride and about 4 to 5% ceftazidime loss in the samples stored at 24 C in 24 hours. Vancomycin hydrochloride losses of 3% or less and ceftazidime loss of about 6% were found in the samples stored at 37 C for 12 hours. No difference in stability was found between samples at either dextrose concentration. (2217) Also see Vancomycin below.

Ceftazidime (GlaxoWellcome) 0.125 mg/mL in Delflex peritoneal dialysis solution bags with 2.5% dextrose (Fresenius) was stable by bioassay with 10% loss occurring in 7 days at refrigerator temperature and 3 days at room temperature. (2573)

Aminoglycosides The manufacturers recommend that ceftazidime not be admixed with aminoglycosides because of the potential for interactions. (1-1/07) (1-2/07) (4)

Pennell et al. evaluated the potential for inactivation of tobramycin sulfate (Tazidime, Lilly) 9 g/mL with 100- and 200-g/mL concentrations of ceftazidime (Lilly) in human serum. No loss of tobramycin sulfate was determined by TDx fluorescence polarization immunoassay over 48 hours when stored at 4, 24, and 37 C. (1420)

The in vivo activities of amikacin sulfate and gentamicin sulfate administered with ceftazidime were evaluated in volunteers. Microbiological assays found no statistically significant reductions in aminoglycoside blood levels in the aminoglycoside-ceftazidime combinations. (504)

Tobramycin sulfate 10 g/mL was also evaluated as in vitro solutions for inactivation potential with aztreonam, ceftazidime, and imipenem, each at a concentration of 100 g/mL in water. Little or no loss of activity of any of the antibiotics was found in 24 hours at 37 C using HPLC (for the -lactam antibiotics) and enzyme-mediated immunoassay technique (EMIT) for the tobramycin as well as microbiological plate assays. (498)

Vancomycin The compatibility or incompatibility of vancomycin hydrochloride mixed with or administered simultaneously with ceftazidime is concentration dependent. (2189) See Y-Site Compatibility above. Vancomycin hydrochloride has a low pH and is variably compatible with drugs having neutral to mildly alkaline pH, including cephalosporins and penicillins. The compatibility may depend on a number of factors, including concentration of each drug, dilution vehicle, actual pH of solutions, and completeness of mixing during administration. Combinations that are compatible when well mixed may result in precipitation if only partially mixed, presumably because of regionally different concentrations and pH values. If attempting to administer vancomycin hydrochloride with ceftazidime, take care to ensure that the specific combination and the concentrations are compatible under the exact administration conditions to be used. An inline filter should be used as a final safety measure. (2189)

A precipitate formed instantaneously when ceftazidime 2 g/50 mL of sterile water for injection was added to a burette previously used to administer vancomycin hydrochloride 1 g/100 mL of

dextrose 5%. The authors suggested that vancomycin may have precipitated because of the alkaline pH due to the sodium carbonate in the ceftazidime formulation, (873) although similar results occurred with the l-arginine formulation that contained no sodium carbonate.

Other Drugs Ceftazidime 4 mg/mL in sodium chloride 0.9% and dextrose 5% is stated to be stable for 24 hours at room temperature or seven (Fortaz) or 10 (Tazidime) days under refrigeration when admixed with heparin 10 or 50 units/mL, potassium chloride 10 or 40 mEq/L, or cefuroxime 3 mg/mL. (4)

Tazicef 20 mg/mL in sterile water for injection is stated to be stable for 18 hours at room temperature or seven days under refrigeration when admixed with cefazolin sodium 330 mg/mL, cimetidine 150 mg/mL, or heparin 1000 units/mL. At 20 mg/mL in dextrose 5%, Tazicef is stated to be stable for 24 hours at room temperature or seven days refrigerated when admixed with potassium chloride 40 mEq/L. (4)

References






ISBN: o ISBN-13: 978-1-58528-213-5








Location In Title:

o HANDBOOK ON INJECTABLE DRUGS - 15th Ed. (2009) "C" Monographs Ceftazidime - AHFS 8:12.06.12


Fentanyl Citrate - AHFS 28:08.08

Products Fentanyl citrate is available in 2-, 5-, 10-, and 20-mL ampuls, 2- and 5-mL syringe cartridges, and 30- and 50-mL vials. (29) (154) Each milliliter contains fentanyl (as the citrate) 50 g (0.05 mg) with hydrochloric acid and/or sodium hydroxide for pH adjustment. (1-8/05) (4)

pH From 4 to 7.5. (1-8/05) (4)

Osmolality The product osmolality was determined to be essentially 0 mOsm/kg. (1233)

Trade Name(s) Sublimaze

Administration Fentanyl citrate is administered by intramuscular or intravenous injection. (1-8/05)

Stability Intact containers should be stored at controlled room temperature and protected from light. Brief exposure to temperatures up to 40 C does not affect potency. (1-8/05) (4)

pH Effects Fentanyl citrate is most stable at pH 3.5 to 7.5. (1638) Fentanyl is hydrolyzed in acidic solutions. (4)

Syringes Fentanyl citrate (Elkins Sinn) 0.0167 mg/mL in sodium chloride 0.9% packaged in polypropylene syringes (Sherwood) was physically stable and exhibited little or no loss by stability-indicating HPLC analysis in 24 hours stored at 4 and 23 C in the dark. (2199)

/w EPDw ULLTE4N

Fentanyl citrate (David Bull) at a concentration of 12.5 g/mL in sodium chloride 0.9% was packaged as 8 mL in 10-mL polypropylene syringes (Terumo) with 19-gauge needles attached (Becton-Dickinson). Fentanyl citrate (David Bull) at a concentration of 33.3 g/mL in sodium chloride 0.9% was packaged as 18 mL in 20-mL polypropylene syringes (Terumo) with 19-gauge needles attached (Becton-Dickinson). The syringes were stored refrigerated at 5 C, at 22 C exposed to light, and at 38 C for seven days. The solutions were visually unchanged, and HPLC analysis found no loss at 5 and 22 C. At 38 C, the 12.5-g/mL solution exhibited less than 7% loss, whereas the 33.3-g/mL solution had no loss in seven days. (2202)

Fentanyl citrate (Janssen) 35 g/mL in sodium chloride 0.9% was packaged in two types of polypropylene syringes. The Omnifix (B. Braun) syringes had polyisoprene piston tips while the Terumo syringes had no natural or synthetic rubber in the product. Stored at 4, 21, and 35 C for 30 days, the test solutions exhibited no visual changes or changes in measured pH. Although the pH remained within the stability range for the drug, this does not definitively demonstrate stability. (2387)

Undiluted fentanyl citrate 50 mcg/mL was tested for stability in polypropylene syringes. The fentanyl citrate injection was filled into polypropylene syringes that were then capped off. The samples were stored for 28 days under refrigeration at 5 C and at room temperature of 22 C exposed to light. No change in color or clarity occurred. No loss of fentanyl citrate at either set of storage conditions occurred when evaluated using stability-indicating HPLC analysis. (2648)

Ambulatory Pumps Fentanyl citrate (Janssen) 20 g/mL in sodium chloride 0.9% in PVC portable infusion pump reservoirs exhibited little or no loss after 30 days at 23 and 3 C. Wrapping the reservoirs to prevent possible moisture loss was not necessary for storage of 30 days. (1356)

Fentanyl citrate (Merck) 50 and 30 mcg/mL diluted in sodium chloride 0.9% was evaluated in CADD-1 and CADD-PRIZM medication cassettes. HPLC analysis found about 4% drug loss occurred in 14 days at room and refrigeration temperatures. (2717)

Elastomeric Reservoir Pumps Fentanyl citrate 1 to 5 g/mL in dextrose 5% or in sodium chloride 0.9% in Infusor elastomeric reservoir pumps has been stated by the pump manufacturer to be stable for 90 days under refrigeration followed by 14 days at room temperature and then followed by seven additional days at 37 C. The manufacturer also has indicated that these fentanyl citrate solutions are stable for 30 days at room temperature followed by seven days at 37 C. (31)

Sorption Fentanyl citrate (Janssen) 5 g/mL in dextrose 5% or sodium chloride 0.9% exhibited no loss due to sorption to PVC infusion solution containers when compared to glass containers. Furthermore, use of a PCA infusion pump to deliver fentanyl citrate 4.5 g/mL in dextrose 5% in a PVC bag did not result in concentration losses associated with sorption. Delivered concentrations were relatively consistent during the 30-hour evaluation period. (1357)

Xu et al. reported extensive and rapid loss of fentanyl citrate due to sorption to PVC containers when the solution pH was adjusted to the alkaline range. Fentanyl citrate 12.5 g/mL in both dextrose 5% and sodium chloride 0.9% at pH 9 (with added sodium hydroxide) or combined

with fluorouracil with nearly the same pH lost 25% of the fentanyl content in 15 minutes and 50% in one hour by HPLC analysis. Loss of fentanyl citrate did not occur in polyethylene containers under these conditions. Sorptive loss of fentanyl citrate to PVC containers is expected to occur from any alkaline solution. (2064)

Fentanyl citrate 2 g/mL in various buffer solutions ranging from pH 5.5 to pH 6.7 packaged in PVC containers (Baxter) was shown to undergo slow sorption to the PVC in amounts dependent on the pH of the solution. The lower pH solutions exhibited less loss with increasing loss as the pH increased. At the highest pH tested of 6.7, 17% fentanyl loss occurred in one day. Refrigeration decreased the extent of loss but did not eliminate it. See Table 1. Little or no fentanyl loss was found in identical fentanyl citrate 2-g/mL solutions packaged in glass containers. (2305)

Undiluted fentanyl citrate 50 mcg/mL was tested for stability in PVC bags. The fentanyl citrate injection was filled into PVC bags that were stored for 28 days under refrigeration at 5 C and at room temperature of 22 C exposed to light. No change in color or clarity occurred. No loss of fentanyl citrate at either set of storage conditions occurred when evaluated using stability-indicating HPLC analysis. (2648)

Table 1. Percentage of Fentanyl Citrate 2 g/mL Remaining After Storage for 30 Days at 23 C in PVC Containers 2305 Buffer pH Fentanyl Remaining (%)

5.5 855.8 776.3 566.7 27

Filtration Fentanyl citrate (Janssen) 2.5 g/mL in dextrose 5% or sodium chloride 0.9% was delivered over four hours through three kinds of 0.2-m membrane filters varying in size and composition. HPLC analysis of the delivered solution showed no fentanyl loss due to sorption to the filter. (1399)

Central Venous Catheter Fentanyl citrate (Abbott) 10 g/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. HPLC analysis was used to evaluate completeness of drug delivery through the catheter and the amount of chlorhexidine removed from the internal lumens. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter. (2335)



Fentanyl citrateSolution Mfr Mfr Conc/L Remarks Ref C/I

Dextrose 5% DB,a TRb JN 5 mg Physically compatible with no fentanyl loss in

48 hr at 22 C in normal room light 1357 C

Dextrose 5% AB JN 20 and 40 mg

Visually compatible with 3% or less loss by HPLC in 3 hr at 24 C 1852 C

Sodium chloride 0.9% TRb JN 20 mg Physically compatible with little or no fentanyl

loss in 30 days at 3 and 23 C 1356 C


DB,a TRb JN 5 mg Physically compatible with no fentanyl loss in

48 hr at 22 C in normal room light 1357 C

aTested in glass containers.

bTested in PVC containers.


Fentanyl citrate

Drug Mfr Conc/L Mfr Conc/L Test Soln Remarks Ref C/I

Bupivacaine HCl WI 1.25 g JN 20 mg NSa

Physically compatible with little or no loss of either drug in 30 days at 3 and 23 C

1396 C

1.25 g 2 mg NSa

Physically compatible with no bupivacaine loss and about 6 to 7% fentanyl loss by HPLC in 30 days at 4 and 23 C

2305 C

600 mg 2 mg NSa

Physically compatible with no bupivacaine loss and about 2 to 4% fentanyl loss by HPLC in 30 days at 4 and 23 C

2305 C

Bupivacaine HCl with clonidine HCl

AST BI

1 g 9 mg JN 35 mg NSa

Visually compatible with less than 10% change of any drug in 28 days at 4 C and 24 days at 25 C in the dark

2437 C

Bupivacaine HCl with epinephrine bitartrate

IVX 1 g 2 mg IVX 2 mg

Visually compatible with less than 10% loss of epinephrine and no loss of other drugs in 182 days at 4 and 22 C

2613 C

Droperidol and ketamine HCl

JA JA

50 mg 1 g DB 10 mg NSa

Visually compatible with about 5% increase in all of the drug concentrations in 30 days at both 4 and 25 C due to loss of moisture

2653 C

JA JA

50 mg 1 g DB 10 mg NSd

Visually compatible with little or no loss of the drug concentrations in 30 days at 25 C

2653 C

Fluorouracil AB 1 and 16 g AB 12.5 mg D5W,

NSa25% fentanyl loss in 15 min due to sorption to PVC 2064 I

Lidocaine HCl AST 2.5 g 2 mg NSaPhysically compatible with no loss of either drug by HPLC in 30 days at 4 and 23 C

2305 C

BRN 2.5 g 2 mg NSa

Physically compatible with little lidocaine loss but 18% fentanyl loss by HPLC at 23 C and 10% loss at 4 C in 2 days due to sorption at pH 6.7 from higher pH lidocaine product

2305 I

Ropivacaine HCl AZ 1 g JN 1 mg NSb

Visually and microscopically compatible with no loss of either drug in 30 days at 30 C in the dark

2433 C

AZ 2 g JN 1 and 10 mg

b


2433 C

ASZ 1.5 g CUR 3 mg NSc

Physically compatible with no loss of either drug in 51 days at 20 C in light or dark and refrigerated

2498 C

ASZ 1.5 g CUR 3 mg NSaPhysically compatible with no loss of either drug in 7 days at 20 C in light or dark and refrigerated

2498 C

aTested in PVC containers.

bTested in polypropylene bags (Mark II Polybags).

cTested in glass and ethylene vinyl acetate containers.

dTested in glass containers.


Fentanyl citrateDrug (in syringe) Mfr Amt Mfr Amt Remarks Ref C/I

Atracurium besylate BW 10 mg/mL 50 g/mL

Physically compatible and atracurium chemically stable for 24 hr at 5 and 25 C

1694 C

Atropine sulfate 0.6 mg/1.5 mL MN 100 g/1

mLPhysically compatible for at least 15 min 14 C

ST 0.4 mg/1 MN 0.05 Physically compatible for at 326 C

mL mg/1 mL least 15 min


AST BI

50 mg 0.45 mg JN 1.75 mg

Diluted to 50 mL with NS. Visually compatible with less than 10% loss of any drug in 25 days at 4 and 25 C in the dark

2437 C

Bupivacaine HCl with ketamine HCl

SW PD

1.5 mg/mL 2 mg/mL

JN 0.01 mg/mL

Diluted to 5 mL with NS. Visually compatible with no new GC/MS peaks in 1 hr at room temperature

1956 C

Butorphanol tartrate BR 4 mg/2 mL MN 0.1 mg/2

mL

Physically compatible both macroscopically and microscopically for 30 min at room temperature

566 C

Caffeine citrate 20 mg/1 mL ES 50 g/1

mLVisually compatible for 4 hr at 25 C 2440 C

Chlorpromazine HCl PO 50 mg/2 mL MN 0.05

mg/1 mLPhysically compatible for at least 15 min 326 C

Cimetidine HCl SKF 300 mg/2 mL JN 0.1 mg/2

mLPhysically compatible for 4 hr at 25 C 25 C

Clonidine HCl with lidocaine HCl

BI AST

0.03 mg/mL 2 mg/mL

JN 0.01 mg/mL

Diluted to 5 mL with NS. Visually compatible with no new GC/MS peaks in 1 hr at room temperature

1956 C

Dimenhydrinate HR 50 mg/1 mL MN 0.05


Diphenhydramine HCl PD 50 mg/1

mL MN 0.05 mg/1 mL

Physically compatible for at least 15 min 326 C

Droperidol MN 2.5 mg/1 mL MN 0.05


Heparin sodium 2500 units/1 mL JN 0.1 mg/2


Hydromorphone HCl KN 4 mg/2 mL MN 0.05

mg/1 mLPhysically compatible for 30 min 517 C

Hydroxyzine HCl PF 50 mg/1 mL MN 0.05


PF 50 mg/1 mL CR 0.05

mg/1 mL Physically compatible 771 C

PF 100 mg/2 mL CR 0.05

mg/1 mL Physically compatible 771 C

Meperidine HCl WI 50 mg/1 mL MN 0.05


Metoclopramide HCl NO 10 mg/2 mL MN 0.05

mg/1 mL


565 C

Metoclopramide HCl with midazolam HCl

AST RC

20 mg/4 mL 15 mg/3 mL

DB 1 mg/20 mL

Visually compatible with 7% or less loss of each drug in 10 days at 32 C

2268 C

Midazolam HCl RC 5 mg/1 mL ES 0.1 mg/2

mLPhysically compatible for 4 hr at 25 C under fluorescent light 1145 C

RC0.625 and 0.938 mg/mLa

DB 12.5 g/mLa

Visually compatible with little fentanyl loss and 7 to 9% midazolam loss by HPLC in 7 days at 5 and 22 C, respectively

2202 C

RC 0.625 mg/mLa DB 37.5

g/mLa

Visually compatible with no fentanyl loss and 5 to 8% midazolam loss by HPLC in 7 days at 5 and 22 C, respectively

2202 C

RC 0.938 mg/mLa DB 37.5

g/mLa

Visually compatible with little fentanyl loss and 7 to 9% midazolam loss by HPLC in 7 days at 5 and 22 C, respectively

2202 C

RC0.278 and 0.833 mg/mLa

DB 33.3 g/mLa

Visually compatible with no fentanyl loss and not more than 5 to 7% midazolam loss by HPLC in 7 days at 5 and 22 C, respectively

2202 C

Morphine sulfate ST 15 mg/1 mL MN 0.05


Ondansetron HCl GW 1.33 mg/mLa ES 0.0167

mg/mLa

Physically compatible with no measured increase in particulates and little or no loss of either drug by HPLC in 24 hr at 4 or 23 C

2199 C

Pantoprazole sodium 4 mg/1 mL 50 g/1

mLPossible precipitate within 15 min 2574 I

Papaveretum RCb 20 mg/1 mL MN 0.05

mg/1 mLVisually compatible for at least 15 min 326 C

Pentazocine lactate WI 30 mg/1 mL MN 0.05


Pentobarbital sodium AB 50 mg/1 mL MN 0.05

mg/1 mLPhysically incompatible within 15 min 326 I

Prochlorperazine edisylate PO 5 mg/1

mL MN 0.05 mg/1 mL


Promazine HCl WY 50 mg/1 mL MN 0.05


Promethazine HCl PO 50 mg/2 mL MN 0.05


Ranitidine HCl GL 50 mg/2 mL

JN 0.1 mg/2 mL

Physically compatible for 1 hr at 25 C both macroscopically and

978 C

microscopicallyScopolamine butylbromide with midazolam HCl

BI RC

30 mg/1.5 mL 15 mg/3 mL

DB 1 mg/20 mL

Visually compatible with 9% or less loss of each drug in 7 days at 32 C

2268 C

Scopolamine HBr 0.6 mg/1.5 mL MN 100 g/1


ST 0.4 mg/1 mL MN 0.05


aTested in sodium chloride 0.9%.

bThe former formulation was tested.


Fentanyl citrateDrug Mfr Conc Mfr Conc Remarks Ref C/I

Abciximab LI 36 g/mLa AB 50 g/mLVisually compatible for 12 hr at 23 C under fluorescent light

2374 C

Amiodarone HCl WY 6 mg/mLa BA 50 g/mL Visually compatible for 24 hr at 22 C 2352 C

Amphotericin B cholesteryl sulfate complex

SEQ 0.83 mg/mLa AB 0.05

mg/mL

Physically compatible with little or no change in measured turbidity or increase in particle content in 4 hr at 23 C under fluorescent light

2117 C

Anidulafungin VIC 0.5 mg/mLa AB 50 g/mL

Physically compatible with no change in measured turbidity or increase in particle content in 4 hr at 23 C

2617 C

Argatroban GSK 1 mg/mLb ES 50 g/mL Visually compatible for 24 hr at 23 C 2391 C

Atracurium besylate BW 0.5 mg/mLa ES 10 g/mLa Physically compatible for 24 hr at 28 C 1337 C

Atropine sulfate LY 0.4 mg/mL JN 0.025 mg/mLa

Physically compatible with no change in measured haze or increase in particle content in 48 hr at 22 C

1706 C

Azithromycin PF 2 mg/mLb AB 50 g/mLiWhitish-yellow microcrystals found upon filter inspection

2368 I

Bivalirudin TMC 5 mg/mLa AB 50 g/mL Physically compatible with 2373 C

no increase in measured haze or particle content in 4 hr at 23 C under fluorescent light

TMC 5 mg/mLab TAY 50 g/mL Visually compatible for 6 hr at 23 C 2680 C

Cisatracurium besylate GW 0.1, 2, 5 mg/mLa AB 0.0125

mg/mLa


2074 C

Clonidine HCl BI 18 mcg/mLb ALP 50

mcg/mL Visually compatible 2642 C

Dexamethasone sodium phosphate AMR 1 mg/mLa JN 0.025

mg/mLa


1706 C

Diazepam ES 0.5 mg/mLa JN 0.025 mg/mLa


1706 C

Diltiazem HCl MMD 1 mg/mLa ES 0.05 mg/mL

Visually compatible for 4 hr at 27 C 2062 C

Diphenhydramine HCl SCN 2 mg/mLa JN 0.025 mg/mLa


1706 C

Dobutamine HCl LI 4 mg/mLa ES 0.05 mg/mL


Dopamine HCl AB 3.2 mg/mLa ES 0.05 mg/mL


Doxapram HCl RB 2 mg/mLa ESL 25 g/mLa Visually compatible for 4 hr at 23 C 2470 C

Enalaprilat MSD 0.05 mg/mLb ES 2 g/mLa

Physically compatible for 24 hr at room temperature under fluorescent light

1355 C

Epinephrine HCl AB 0.02 mg/mLa ES 0.05

mg/mLVisually compatible for 4 hr at 27 C 2062 C

Esmolol HCl DCC 1 g/100 mLc JN 0.05 mg/1

mL

Physically compatible when fentanyl is injected into Y-site of flowing admixtured

1168 C

DCC 10 mg/mLc JN 0.05 mg/mL

Physically compatible with no loss of either drug in 8 hr at ambient temperature exposed to light

1168 C

Etomidate AB 2 mg/mL ES 0.05 mg/mL

Visually compatible for up to 7 days at 25 C 1801 C

Fenoldopam mesylate AB 80 g/mLb AB 12.5 g/mLb

Physically compatible with no increase in measured haze or particle content in 4 hr at 23 C under fluorescent light

2467 C

Furosemide AMR 10 mg/mL ES 0.05 mg/mL


Haloperidol lactate MN 0.2 mg/mLa JN 0.025 mg/mLa


1706 C

Heparin sodium UP 1000 units/Le MN 0.05

mg/mL

Physically compatible for at least 4 hr at room temperature by visual and microscopic examination

534 C

ES 100 units/mLa ES 0.05


Hetastarch in lactated electrolyte injection (Hextend)

AB 6% ES 12.5 g/mLa


2339 C

Hydrocortisone sodium succinate UP 10 mg/Le MN 0.05

mg/mL


534 C

Hydromorphone HCl KN 1 mg/mL ES 0.05 mg/mL


Hydroxyzine HCl WI 4 mg/mLa JN 0.025 mg/mLa


1706 C

Ketorolac tromethamine WY 1 mg/mLa JN 0.025

mg/mLa


1706 C

Labetalol HCl SC 1 mg/mLa JN 10 g/mLa Physically compatible for 24 hr at 18 C 1171 C

AH 2 mg/mLa ES 0.05 mg/mL


Levofloxacin OMN 5 mg/mLa AB 0.05 mg/mL

Visually compatible for 4 hr at 24 C under fluorescent light

2233 C

Linezolid PHU 2 mg/mL AB 0.05 mg/mL


2264 C

Lorazepam WY 0.33 mg/mLb 0.05


WY 0.5 mg/mLa ES 0.05 mg/mL


WY 0.1 mg/mLa JN 0.025 mg/mLa


1706 C

Methotrimeprazine HCl LE 0.2 mg/mLa JN 0.025

mg/mLa


1706 C

Metoclopramide HCl DU 5 mg/mL JN 0.025 mg/mLa


1706 C

Midazolam HCl RC 1 mg/mLa ES 0.05 mg/mL


RC 0.1 and 0.5 mg/mLa JN 0.02

mg/mLa

Visually compatible with no midazolam loss and 3 to 4% fentanyl loss by HPLC in 3 hr at 24 C

1852 C

RC 0.1 and 0.5 mg/mLa JN 0.04

mg/mLa

Visually compatible with no loss of either drug by HPLC in 3 hr at 24 C

1852 C

RC 5 mg/mL 0.05 mg/mL


RC 2 mg/mLa ES 0.05 mg/mL


RC 0.2 mg/mLa JN 0.025 mg/mLa


1706 C

Milrinone lactate SW 0.2 mg/mLa ES 0.05 mg/mL


SW 0.4 mg/mLa ES 50 g/mL

Visually compatible with little or no loss of either drug by HPLC in 4 hr at 23 C

2214 C

Morphine sulfate SCN 2 mg/mLa ES 0.05 Visually compatible for 4 hr 2062 C

mg/mL at 27 C

Nafcillin sodium WY 33 mg/mLb 0.05 mg/mL No precipitation 547 C

Nesiritide SCI 50 mcg/mLab 0.05

mg/mLPhysically compatible for 4 hr 2625 C

Nicardipine HCl WY 1 mg/mLa ES 0.05 mg/mL


DCC 0.1 mg/mLa ES 2 g/mLa Visually compatible for 24 hr at room temperature 235 C

Nitroglycerin AB 0.4 mg/mLa ES 0.05 mg/mL


Norepinephrine bitartrate AB 0.128

mg/mLa ES 0.05 mg/mL


Oxaliplatin SS 0.5 mg/mLa AB 0.05 mg/mLa


2566 C

Palonosetron HCl MGI 50 mcg/mL AB 50 mcg/mL

Physically compatible with no change in measured haze level or increase in particle content and no palonosetron or fentanyl loss

2720 C

Pancuronium bromide ES 0.05 mg/mLa ES 10 g/mLa Physically compatible for

24 hr at 28 C 1337 C

Phenobarbital sodium WY 2 mg/mLa JN 0.025 mg/mLa


1706 C

Phenytoin sodium ES 2 mg/mLab JN 0.025 mg/mLa

Precipitate forms within 1 hr 1706 I

Potassium chloride AB 40 mEq/Le MN 0.05 mg/mL


534 C

Propofol ZEN 10 mg/mL AB 0.05 mg/mL

Physically compatible for 1 hr at 23 C with no increase in particle content

2066 C

Ranitidine HCl GL 1 mg/mLa ES 0.05 mg/mL


Remifentanil HCl GW0.025 and 0.25 mg/mLb

ES 0.0125 mg/mLa


2075 C

Sargramostim IMM 6f and 15 g/mLb ES 50 g/mL Visually compatible for 2 hr 1618 C

Scopolamine HBr LY 0.05 mg/mLa JN 0.025

mg/mLa


1706 C

Thiopental sodium AB 25 mg/mL ES 0.05 mg/mL


AB 25 mg/mLg ES 0.05 mg/mL


TNA #218 to #226h AB0.0125a and 0.05 mg/mL

Visually compatible with no precipitate or emulsion damage apparent in 4 hr at 23 C

2215 C

TPN #203 and TPN #204h ES 0.05


TPN #212 to #215h AB 0.05 mg/mL


2109 C

JN 0.0125 mg/mLa


2109 C

TPN #216h ES 0.01 mg/mLg

Mixed 1 mL of fentanyl with 9 mL of TPN. Visually compatible for 24 hr

2104 C

Vecuronium bromide OR 0.1 mg/mLa ES 10 g/mLa Physically compatible for 24 hr at 28 C 1337 C

OR 1 mg/mL ES 0.05 mg/mL


Vitamin B complex with C RC 2 mL/Le MN 0.05

mg/mL


534 C

aTested in dextrose 5%.

bTested in sodium chloride 0.9%.

cTested in dextrose 5% in sodium chloride 0.9%.

dFlowing at 1.6 mL/min.

eTested in dextrose 5% in Ringer's injection, dextrose 5% in Ringer's injection, lactated, dextrose 5%, Ringer's injection, lactated, and sodium chloride 0.9%.

fTested with albumin human 0.1%.

gTested in sterile water for injection.

hRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3-in-1 admixture, and TPN indicates a 2-in-1 admixture.

iInjected via Y-site into an administration set running azithromycin.


Bupivacaine and Epinephrine A solution composed of bupivacaine hydrochloride (Winthrop) 0.44 mg/mL, fentanyl citrate (Janssen) 1.25 g/mL, and epinephrine hydrochloride (Abbott) 0.69 g/mL was stored in 100-mL portable infusion pump reservoirs (Pharmacia Deltec) for 30 days at 3 and 23 C. The samples were then delivered through the infusion pumps over 48 hours at near-body temperature (30 C). The samples were visually compatible throughout, and bupivacaine hydrochloride and fentanyl citrate exhibited no loss by HPLC analysis. Epinephrine hydrochloride sustained about a 5 to 6% loss by HPLC analysis after 20 days of storage at both temperatures and about a 9 to 10% loss after 30 days of storage and subsequent pump delivery. The authors recommended restricting storage before administration to only 20 days. (1627)

Multiple Drugs A seven-drug combination consisting of bupivacaine hydrochloride (Sanofi Winthrop) 1.5 mg/mL, clonidine hydrochloride (Boehringer Ingelheim) 0.03 mg/mL, fentanyl citrate (Janssen) 0.01 mg/mL, ketamine (Parke-Davis) 2 mg/mL, lidocaine hydrochloride (Astra) 2 mg/mL, morphine sulfate (Elkins-Sinn) 0.2 mg/mL, and tetracaine hydrochloride (Sanofi Winthrop) 2 mg/mL mixed together in equal quantities was found to be visually compatible with no new GC/MS peaks appearing in one hour at room temperature. (1956)

Other Drugs Fentanyl citrate is stated to be physically incompatible with methohexital, pentobarbital, and thiopental. (4)

References


© 2009 American Society of Health-System Pharmacists, Inc. All rights reserved. (+/-) Show / Hide Bibliography Bibliographic Citations Bibliographic Citations

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Or highlight and copy (Ctrl-C) the plain text citation below ............................................................LAWRENCE A. TRISSEL, F.A.S.H.P.. 2009. Handbook on Injectable Drugs. Bethesda, MD. American Society of Health-System Pharmacists. ISBN-13: 978-1-58528-213-5. STAT!Ref Online Electronic Medical Library. http://online.statref.com/document.aspx?fxid=141&docid=149. 8/21/2010 2:46:30 AM CDT (UTC -05:00).




ISBN: o ISBN-13: 978-1-58528-213-5





Date Posted: o 11/4/2009 4:31:06 PM CDT (UTC -05:00)


Date Accessed: o 8/21/2010 2:46:30 AM CDT (UTC -05:00)


"F" Monographs Fentanyl Citrate - AHFS 28:08.08


Fosfomycin Disodium - AHFS 8:36

Products Fosfomycin disodium is available in vials containing the equivalent of 1 g of fosfomycin as the disodium salt with an accompanying 10-mL ampul of diluent for reconstitution and in vials containing the equivalent of 4 g of fosfomycin as the disodium salt with an accompanying 20-mL ampul of diluent for reconstitution. Also present in the formulation is succinic acid. (116)

Sodium Content Fosfomycin disodium contains 14.4 mEq or mmol (330 mg) of sodium per gram of drug product. (116)

Trade Name(s) Fosfocine

Administration Fosfomycin disodium is administered intramuscularly (5) and by intravenous infusion after dilution of the reconstituted product in a compatible infusion solution. A recommended minimum volume for dilution for infusion is 250 mL. (5) (116)

Stability The reconstituted drug in vials and the solution diluted for infusion in dextrose 5% or sodium chloride 0.9% are stable for 24 hours at room temperature. (116)

Syringes Fosfomycin disodium diluted to concentrations of 50 mg/1 mL and 50 mg/3 mL in water for injection were packaged in infusion pump syringes (Braun Melsungen) and were evaluated for stability under a variety of storage conditions. The stability results are presented in Table 1. No concentration dependency was found, but exposure to light appeared to increase the rate of decomposition. (2303)

Table 1. Stability of Fosfomycin Disodium 50 mg/1 mL and 50 mg/3 mL in Water for Injection in Infusion Pump Syringes 2303

Storage Conditions and Durations Fosfomycin Remaining

Room temperature, light protected for 6 hr 97 to 98%Room temperature, light exposed for 8 hr 88 to 91%Refrigerated at 4 to 8 C for 96 hr plus room tempera ture, light protected for 6 hr 95 to 96%

Frozen at -20 C for 31 days plus 4 to 8 C for 96 hr plus room temperature, light protected for 6 hr 94 to 95%



/w EPDw ULLTE4N

Fosfomycin disodium


Ciprofloxacin Physically incompatible with loss of ciprofloxacin reported due to pH over 6.0

1924 I


Fosfomycin disodiumDrug (in syringe) Mfr Amt Mfr Amt Remarks Ref C/I

Heparin sodium 2500 units/1 mL BM 3 g Visually compatible for at least 5 min 1053 C

References



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"F" Monographs Fosfomycin Disodium - AHFS 8:36


Ganciclovir Sodium - AHFS 8:18.32

Products Ganciclovir sodium is available in vials containing, in dry form, the equivalent of ganciclovir 500 mg. Reconstitute with 10 mL of sterile water for injection and shake to dissolve the drug to yield a solution containing ganciclovir 50 mg/mL. Do not use paraben-containing diluents to reconstitute ganciclovir sodium because precipitation may result. (1-1/06)

pH Approximately 11. (1-1/06)

Sodium Content Each 500-mg vial contains 46 mg of sodium. (1-1/06)

Trade Name(s) Cytovene-IV

/w EPDw ULLTE4N

Administration Ganciclovir sodium is administered by intravenous infusion. After reconstitution, the required dose may be diluted in 50 to 250 mL (usually 100 mL) of compatible infusion solution and given over one hour. Concentrations greater than 10 mg/mL are not recommended. Ganciclovir sodium should not be administered by intramuscular, subcutaneous, or rapid intravenous injection or infusion. (1-1/06) (4)

Stability According to the manufacturer, intact vials should be stored at controlled room temperature and protected from temperatures above 40 C. The reconstituted solution is stable for 12 hours at room temperature. Refrigeration of the reconstituted solution is not recommended because of the possibility of precipitation. (1-1/06) (4) However, Heni reported that ganciclovir sodium 500 mg/10 mL in sterile water for injection was stable, with no significant loss by HPLC analysis, for 60 days when stored at 4 C. (1637)

Freezing Solutions The manufacturer does not recommend freezing ganciclovir sodium solutions. (1-1/06) However, ganciclovir sodium (Syntex) 1.4, 4, and 7 mg/mL in sodium chloride 0.9% packaged in polypropylene syringes and 0.28 and 1.4 mg/mL in sodium chloride 0.9% packaged in PVC containers was evaluated. All samples exhibited 4% or less drug loss by HPLC analysis after 364 days at -20 C. (1836)

In another study, HPLC analysis found no ganciclovir sodium loss from a 10-mg/mL solution in sodium chloride 0.9% in 48 weeks when stored frozen at -8 C. (2595)

Syringes Ganciclovir sodium (Syntex) 5.8 mg/mL in sodium chloride 0.9%, packaged in polypropylene infusion-pump syringes (Healthtek), exhibited 3% or less drug loss in 10 days at 4 C and no loss in 12 hours at 25 C by HPLC analysis. (1742)

Ganciclovir sodium (Syntex) 1.4, 4, and 7 mg/mL in sodium chloride 0.9% was packaged in polypropylene syringes and stored at 20, 4, and -20 C. HPLC analysis found 4% or less drug loss in seven days at 20 C, in 80 days at 4 C, and in 364 days at -20 C. (1836)

Ambulatory Pumps Ganciclovir sodium (Roche) 1 and 5 mg/mL in sodium chloride 0.9% was stored in latex pump reservoirs (Baxter Intermate) and PVC pump reservoirs (I-Flow Sidekick) as well as PVC minibags for comparison. No loss of ganciclovir by HPLC analysis occurred in any of the containers over 35 days stored at 4 C protected from light. The particulate burdens of each container system did vary however. The PVC minibag and PVC Sidekick pump reservoir developed 20-fold increases in microparticulates, mostly of 10 m or less, while the solution latex reservoir did not develop a substantial increase in particulates. The authors attributed this increase in particle burden in PVC to an interaction of the high pH of the ganciclovir solution with PVC. (2251)

Elastomeric Reservoir Pumps Ganciclovir sodium (Syntex) 5 mg/mL in sodium chloride 0.9% 100 mL was packaged in latex elastomeric reservoirs (Secure Medical). About 4 to 6% loss by HPLC analysis occurred in 24 hours at 25 C and in five days at 5 C. (1970)

Ganciclovir sodium solutions in elastomeric reservoir pumps have been stated by the pump manufacturers to be stable for the following time periods refrigerated (REF) or at room temperature (RT) (31) :

Pump Reservoir(s) Conc. REF RTHomepump; Homepump Eclipse 5 mg/mLb 15 days 24 hrIntermate HPC 2 to 5 mg/mLb 7 days 1 to 6 mg/mLab 15 days 24 hrMedflo 5 mg/mLb 35 days 35 daysReadyMed 5 mg/mLb 15 days 48 hraIn dextrose 5%.bIn sodium chloride 0.9%.

Also see Ambulatory Pumps section above.

Sorption During a solution stability study, no sorption to PVC containers was noted. (1288)

Central Venous Catheter Ganciclovir sodium (Roche) 5 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. HPLC analysis was used to evaluate completeness of drug delivery through the catheter and the amount of chlorhexidine removed from the internal lumens. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter. (2335)



Ganciclovir sodiumSolution Mfr Mfr Conc/L Remarks Ref C/I

Dextrose 5% TRa SY 2.44 g

Physically compatible and chemically stable with no drug loss in 5 days at 25 C exposed to light or in the dark and at 4 C

1288 C

Dextrose 5% BAa SY 1, 5, 10 g Visually compatible with 3 to 7% ganciclovir loss by

HPLC in 35 days at 4 to 8 C in the dark 1545 C

Dextrose 5% ABa SY 1 and 5 g Visually compatible with 1% or less ganciclovir loss

by HPLC in 35 days at 5 and 25 C 1643 C


TRa SY 2.59 gPhysically compatible and chemically stable with no drug loss in 5 days at 25 C exposed to light or in the dark and at 4 C

1288 C


ABa SY 1 and 5 g Visually compatible with 1% or less ganciclovir loss by HPLC in 35 days at 5 and 25 C 1643 C


SY 2.2 g Little or no ganciclovir loss by HPLC in 14 days at 4 C 1637 C

Sodium chloride

a SY 0.28 and 1.4 g

4% or less drug loss by HPLC in 7 days at 20 C, 80 days at 4 C, and 364 days at -20 C

1836 C

0.9%Sodium chloride 0.9%

ABb SY 5 g 4 to 6% loss of drug by HPLC in 24 hr at 25 C and in 5 days at 5 C 1970 C


BAa RC 1 and 5 gNo ganciclovir loss in 35 days at 4 C protected from light. No visible particulates but a substantial increase in microparticulates less than 10 m in size developed

2251 C


BAd RC 1 and 5 g Physically compatible with no ganciclovir loss in 35 days at 4 C protected from light 2251 C

TPN #183c SY 2 g Precipitate forms 1744 ITPN #183 to #185c SY 3 and 5 g Precipitate forms 1744 I


bTested in glass containers and latex elastomeric reservoirs (Secure Medical).

cRefer to Appendix I for the composition of parenteral nutrition solutions. TPN indicates a 2-in-1 admixture.

dTested in latex elastomeric pump reservoirs (Baxter Intermate).


Ganciclovir sodiumDrug Mfr Conc Mfr Conc Remarks Ref C/I

Aldesleukin CHI 33,800 I.U./mLa SY 10

mg/mLaAldesleukin bioactivity inhibited 1857 I

Allopurinol sodium BW 3 mg/mLb SY 20 mg/mLb


1686 C

Amifostine USB 10 mg/mLa SY 20 mg/mLa

Crystalline needles form immediately, becoming a dense flocculent precipitate in 1 hr

1845 I


SEQ 0.83 mg/mLa RC 20

mg/mLa

Physically compatible with little or no change in measured turbidity or increase in particle content in 4 hr at 23 C under fluorescent light

2117 C

Amsacrine NCI 1 mg/mLa SY 20 mg/mLa

Immediate dark orange turbidity 1381 I

Anidulafungin VIC 0.5 mg/mLa

RC 20 mg/mLa

Physically compatible with no change in measured turbidity

2617 C

or increase in particle content in 4 hr at 23 C

Aztreonam SQ 40 mg/mLa SY 20 mg/mLa

White crystalline needles form immediately and become dense flocculent precipitate in 1 hr

1758 I

Cefepime HCl BMS 20 mg/mLa SY 20 mg/mLa

Flocculent precipitate forms immediately 1689 I

Cisatracurium besylate GW 0.1 and 2 mg/mLa SY 20

mg/mLa


2074 C

GW 5 mg/mLa SY 20 mg/mLa

White cloudiness forms immediately 2074 I

Cisplatin BR 1 mg/mL SY 20 mg/mLa

Visually compatible for 4 hr at room temperature under fluorescent light

1685 C

Cyclophosphamide MJ 10 mg/mLa SY 20 mg/mLa


1685 C

Cytarabine UP 50 mg/mL SY 20 mg/mLa

Turbidity and particles form in 30 min, becoming gel-like in 4 hr

1685 I

Docetaxel RPR 0.9 mg/mLa RC 20

mg/mLa


2224 C

Doxorubicin HCl AD 0.2 mg/mLa SY 20

mg/mLaColor changes to deep purple immediately 1685 I

Doxorubicin HCl liposome injection SEQ 0.4

mg/mLa RC 20 mg/mLa

Physically compatible with little or no change in measured turbidity and no increase in particle content in 4 hr at 23 C

2087 C

Enalaprilat MSD 1.25 mg/mL SY 5

mg/mLc

Physically compatible for 4 hr at 21 C under fluorescent light by macroscopic and microscopic examination

1409 C

Etoposide phosphate BR 5 mg/mLa RC 20 mg/mLa


2218 C

Filgrastim AMG 30 g/mLa SY 20 mg/mLa


1687 C

Fluconazole RR 2 mg/mL SY 50 Physically compatible for 24 hr 1407 C

mg/mL at 25 C

Fludarabine phosphate BX 1 mg/mLa SY 20 mg/mLa

Darker color visible under high intensity light within 4 hr 1439 I

Foscarnet sodium AST 24 mg/mL 50 mg/mL Immediate precipitation 1335 I

Gemcitabine HCl LI 10 mg/mLb RC 20

mg/mLb

Subvisual crystals form immediately, becoming a gross precipitate in 1 hr

2226 I

Granisetron HCl SKB 0.05 mg/mLa SY 20

mg/mLa


2000 C

Linezolid PHU 2 mg/mL RC 20 mg/mLa


2264 C

Melphalan HCl BW 0.1 mg/mLb SY 20

mg/mLb


1557 C

Methotrexate sodium AD 15 mg/mLd SY 20

mg/mLa


1685 C

Ondansetron HCl GL 1 mg/mLb SY 20 mg/mLa

Immediate turbidity and precipitation 1365 I

Paclitaxel NCI 1.2 mg/mLa SY 20

mg/mLa

Physically compatible with no change in measured turbidity in 4 hr at 22 C

1556 C

Pemetrexed disodium LI 20 mg/mLb RC 20

mg/mLa


2564 C

Piperacillin sodium-tazobactam sodium LE 40 + 5

mg/mLa SY 20 mg/mLa

Large crystals form in 1 hr and become heavy white precipitate in 4 hr

1688 I

Propofol ZEN 10 mg/mL SY 20 mg/mLa


2066 C


SY 20 mg/mLa


2075 C

Sargramostim IMM 10 g/mLb SY 20 mg/mLb

Few small particles formed in 4 hr in one of two samples 1436 I

Tacrolimus FUJ Significant tacrolimus loss 191 I

within 15 min

Teniposide BR 0.1 mg/mLa SY 20

mg/mLa

Physically compatible with no subvisual haze or particle formation in 4 hr at 23 C

1725 C

Thiotepa IMMe 1 mg/mLa SY 20 mg/mLa


1861 C

TNA #218 to #226f RC 20 mg/mLa

Large amount of white precipitate forms immediately 2215 I

TPN #144f SY 1 and 5 mg/mLa


SY 10 mg/mLa

Heavy precipitate forms within 30 min 1522 I

TPN #183f SY 2 mg/mL Precipitate forms 1744 I

SY 1 mg/mLg

Visually compatible with no ganciclovir loss by HPLC in 3 hr at 24 C under fluorescent light. Less than 10% amino acid loss by HPLC in 2 hr

1744 C

TPN #183 to #185f SY 3 and 5 mg/mL Precipitate forms 1744 I

TPN #184 and TPN #185f SY 2

mg/mLh

Visually compatible with no ganciclovir loss by HPLC in 3 hr at 24 C under fluorescent light. Less than 10% amino acid loss by HPLC in 3 hr

1744 C

TPN #212 to #215f SY 20 mg/mLa

Gross white precipitate forms immediately 2109 I

Vinorelbine tartrate BW 1 mg/mLb SY 20 mg/mLb

White turbid solution with precipitate forms immediately 1558 I



cTested in both dextrose 5% and sodium chloride 0.9%.

dTested in dextrose 5% with sodium bicarbonate 0.05 mEq/mL.

eLyophilized formulation tested.

fRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3-in-1 admixture, and TPN indicates a 2-in-1 admixture.

gGanciclovir sodium concentration after mixing was 0.83 mg/mL.

hGanciclovir sodium concentration after mixing was 1.4 mg/mL.


Infusion Solutions The manufacturer states that ganciclovir sodium is chemically and physically compatible when diluted for intravenous infusion in the following solutions (1-1/06) :

Dextrose 5%

Ringer's injection



The manufacturer recommends that admixtures of ganciclovir sodium in compatible infusion solutions be stored under refrigeration but not frozen. Ganciclovir reconstituted with sterile water for injection and diluted further in sodium chloride 0.9% in PVC bags is physically and chemically stable for up to 14 days when stored under refrigeration at 5 C. However, because of the absence of an antibacterial preservative, use within 24 hours is recommended. (1-1/06)

Amino Acids The addition of ganciclovir sodium to parenteral nutrition admixtures may result in precipitation due to its alkaline pH. It has been recommended that if ganciclovir sodium is to be administered by simultaneous Y-site administration with parenteral nutrition admixtures that the ganciclovir concentration not exceed 0.83 mg/mL for a 1% amino acids solution and not exceed 1.4 mg/mL for 2.5% or higher concentration amino acids solution. However, great care and careful observation should still be undertaken because the potential for precipitation may still remain. (1744)

Other Information

Parabens Ganciclovir sodium is stated to be incompatible with paraben-containing solutions. Reconstitution with bacteriostatic water for injection containing parabens may cause precipitation. (1-1/06)

Microbial Growth Ganciclovir sodium (Syntex) 0.35 mg/mL diluted in sodium chloride 0.9% and stored at 22 C did not exhibit a substantial antimicrobial effect on the growth of four organisms (Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) inoculated into the solution. S. aureus and C. albicans remained viable for 24 hours, and the others remained viable to the end of the study at 120 hours. The author recommended that diluted solutions of ganciclovir sodium be stored under refrigeration whenever possible and that the potential for microbiological growth should be considered when assigning expiration periods. (2160)

References








ISBN: o ISBN-13: 978-1-58528-213-5









"G" Monographs Ganciclovir Sodium - AHFS 8:18.32



Gentamicin Sulfate - AHFS 8:12.02

Products Gentamicin (as the sulfate) is available at a concentration of 40 mg/mL in 2- and 20-mL vials and 1.5- and 2-mL syringe cartridges. The drug is also available at a concentration of 10 mg/mL in 2-mL vials for pediatric use. The products may also contain edetate disodium, sodium bisulfite, and parabens. (1-10/06) (1-7/04) (4) (29)

Gentamicin sulfate is also available from several manufacturers premixed in various concentrations in sodium chloride 0.9% for intravenous infusion. (4)

pH The injection for intravenous or intramuscular administration has a pH of 3 to 5.5. Premixed infusions of gentamicin sulfate in sodium chloride 0.9% have a pH of around 4 to 4.5. (4)

Osmolality Gentamicin sulfate (Wyeth) 40 mg/mL has a reported osmolality of 160 mOsm/kg. (50) Gentamicin sulfate pediatric injection (Elkins-Sinn) 10 mg/mL has a reported osmolality of 116 mOsm/kg by freezing-point depression or 212 mOsm/kg by vapor pressure. (1071)

The osmolality of gentamicin sulfate (SoloPak) 1 mg/mL was determined to be 262 mOsm/kg in dextrose 5% and 278 mOsm/kg in sodium chloride 0.9%. At a 2.5-mg/mL concentration, the osmolality was determined to be 278 mOsm/kg in dextrose 5% and 293 mOsm/kg in sodium chloride 0.9%. (1375)

The osmolality of gentamicin sulfate 80 mg was calculated for the following dilutions (1054) :

Osmolality (mOsm/kg)Diluent 50 mL 100 mL

Dextrose 5% 293 285Sodium chloride 0.9% 320 315

/w EPDw ULLTE4N

The osmolarity of the premixed infusions in sodium chloride 0.9% is approximately 284 to 308 mOsm/L. (4)

Administration Gentamicin sulfate is administered by intramuscular injection or intermittent intravenous infusion over 0.5 to two hours. For adults, intravenous administration after dilution in 50 to 200 mL of sodium chloride 0.9% or dextrose 5% is recommended, while the volume for pediatric patients should be reduced consistent with the patient's needs. (1-10/06) (1-7/04) (4)

Stability Gentamicin sulfate injection is colorless to slightly yellow. (4) Intact containers should be stored at controlled room temperature and protected from freezing. (1-10/06) (1-7/04) (4) Potency loss has been determined to be unrelated to color intensity of gentamicin sulfate solutions. (2139)

Freezing Solutions Gentamicin sulfate (Schering) 50 mg in 50 mL of dextrose 5% and also sodium chloride 0.9% in PVC containers was frozen at -20 C for 30 days. Potency was retained for the duration of the study. (299)

In another study, gentamicin sulfate (Schering) 80 mg/100 mL of dextrose 5% in PVC bags was frozen at -20 C for 30 days and then thawed by exposure to ambient temperature or microwave radiation. No evidence of precipitation or color change was observed, and no loss of potency was determined microbiologically. Subsequent storage of the admixture at room temperature for 24 hours also yielded a physically compatible solution, exhibiting little or no loss of potency. (554)

Marble et al. reported that gentamicin sulfate (Elkins-Sinn) 120 mg/50 mL lost 6% activity in dextrose 5% and 2% activity in sodium chloride 0.9% in 28 days when frozen at -20 C. (981)

Syringes Gentamicin sulfate (Schering) 40 mg/mL was found to retain potency for three months at room temperature when 1 and 2 mL of solution were packaged in Tubex cartridges. (13)

In another report, the stability of gentamicin sulfate (Schering) repackaged in plastic syringes (Monoject) was significantly less than in glass syringes (Glaspak, Becton-Dickinson) at both 4 and 25 C. The commercial concentrations were tested in the following amounts: 40 mg/mL-1, 0.75, 0.5, and 0.25 mL; and 10 mg/mL-1.5, 1, and 0.5 mL. Storage in plastic syringes resulted in an average potency loss of 16% in 30 days and in the formation of a brown precipitate. In glass syringes, the average potency loss was 7% at 30 days. The brown precipitate did not appear after 30 days but was present at 60 days. It appeared in the cannula of the needle in both glass and plastic syringes. For the 40-mg/mL concentration, the volume of the sample also affected stability. Significantly less potency loss was noted in the smaller volumes (0.25 and 0.5 mL) than in the larger volumes (0.5 and 1 mL). This volume-related phenomenon was not demonstrated in the 10-mg/mL pediatric concentration. Storage temperature had no effect on potency during the 90-day study period. The authors recommended that only glass disposable syringes be used for long-term unit dose storage of gentamicin sulfate and that storage not exceed 30 days. (297)

The appearance of this report stimulated the interest of Kresel et al. They packaged gentamicin sulfate 40 mg/1 mL in polypropylene syringes (Plastipak, Becton-Dickinson) and found no significant change in potency by enzymatic assay over 30 days at 4 or 25 C. (401)

In reply, McNealy et al. noted that a different brand of polypropylene syringes had been used in the study and that plastic composition can vary considerably. Further, they disputed the applicability of the enzymatic assay to long-term plastic-stored samples. (402)

The manufacturer also expressed concern about plastic packaging of gentamicin, noting a possibly inadequate oxygen and moisture barrier both through the tip and the walls of the syringe. It was indicated that gentamicin is oxygen sensitive and that depletion of the antioxidant present could result in instability. Further, loss of moisture at the tip could result in occlusion by the dried product. It was noted that disposable syringes are manufactured by Schering with a two-year expiration date. (403)

Zbrozek et al. found that gentamicin sulfate (Elkins-Sinn) 120 mg, diluted with 1 mL of sodium chloride 0.9% to a final volume of 4 mL, was stable (less than 10% loss) when stored in polypropylene syringes (Becton-Dickinson) for 48 hours at 23 C under fluorescent light. (1159)

Nahata et al. studied the stability of gentamicin sulfate (Elkins-Sinn) diluted to 10 mg/mL with sodium chloride 0.9% and stored in glass syringes (Becton-Dickinson) at 4 C. No loss of gentamicin sulfate was found by enzyme-mediated immunoassay during 12 weeks of storage. (1265)

Ambulatory Pumps Tu et al. studied the stability of gentamicin sulfate (Schering) 5.45 mg/mL in dextrose 5% in an ambulatory pump reservoir. The drug-filled reservoirs were stored at -20 C for 30 days and then thawed at 5 C for four days. This thawing was then followed by two days of drug delivery through the pump at 37 C. No visible changes and no gentamicin loss occurred during the entire storage and delivery sequence. Furthermore, plasticizer (DEHP) levels were insignificant. (1490)

Elastomeric Reservoir Pumps Gentamicin sulfate (Lyphomed) 0.8 mg/mL in sodium chloride 0.9% 100 mL was packaged in latex elastomeric reservoirs (Secure Medical). Little or no loss by HPLC analysis occurred in 24 hours at 25 C. (1970)

Gentamicin sulfate 0.6 mg/mL in both dextrose 5% and sodium chloride 0.9% was evaluated for binding potential to natural rubber elastomeric reservoirs (Baxter). No binding was found after storage for two weeks at 35 C with gentle agitation. (2014)

Gentamicin sulfate solutions in elastomeric reservoir pumps have been stated by the pump manufacturers to be stable for the following time periods frozen, refrigerated (REF), or at room temperature (RT) (31) (2043) :

Pump Reservoir(s) Conc. Frozen REF RTIntermate 0.5 to 5 mg/mLab 30 days 10 days 24 hrInfusor 0.8 to 2.4 mg/mLb 17 days 17 daysMedflo 0.8 mg/mLab 4 weeks 4 days 48 hrReadyMed 1 mg/mLb 4 weeks 14 days 48 hraIn dextrose 5%.bIn sodium chloride 0.9%.

Sorption Gentamicin sulfate (Schering) 40 mg/L in sodium chloride 0.9% (Travenol) in PVC bags did not exhibit significant sorption to the plastic during one week of storage at room temperature (15 to 20 C). (536)

In another study, gentamicin sulfate (Schering) 40 mg/L in sodium chloride 0.9% did not exhibit any loss due to sorption during a seven-hour simulated infusion through an infusion set (Travenol) consisting of a cellulose propionate burette chamber and 170 cm of PVC tubing. (606)

The drug was also tested as a simulated infusion over at least one hour by a syringe pump system. A glass syringe on a syringe pump was fitted with 20 cm of polyethylene tubing or 50 cm of Silastic tubing. No drug loss due to sorption was observed with either tubing. (606)

A 25-mL aliquot of gentamicin sulfate (Schering) 40 mg/L in sodium chloride 0.9% was stored in all-plastic syringes composed of polypropylene barrels and polyethylene plungers for 24 hours at room temperature in the dark. No loss of drug due to sorption occurred. (606)

Gentamicin sulfate (Dakota) 1.6 mg/mL in dextrose 5% and in sodium chloride 0.9% was packaged in PVC bags (Macropharma) and in multilayer bags composed of polyethylene, polyamide, and polypropylene (Bieffe Medital). The solutions were delivered through PVC administration sets (Abbott) over one hour and evaluated for drug loss by HPLC analysis. No loss due to sorption to any of the plastic materials was found. (2269)

Filtration The effect of several filters on the delivered concentration of gentamicin sulfate (Roussel) from simulated pediatric infusions was studied by Nazeravich and Otten. A syringe containing dextrose 10% on a syringe pump set at 8.26 mL/hr was connected by intravenous tubing to a 0.5-m air-blocking filter set (Travenol), a 0.22-m air-eliminating filter set (Travenol), and a 0.2-m air-eliminating filter set (Pall). Gentamicin doses of 2.5 and 7.5 mg were injected antegrade to the filter. The effluents were sampled at 1, 1.5, 2, and 4 hours and tested using an enzyme-mediated immunoassay technique (EMIT) assay. No significant drug sorption to the plastic tubing or inline filters occurred. However, because of the difference in specific gravity of the drug (1.010) and intravenous solution (1.032), variations in delivered gentamicin did occur due to filter design and position. With the Travenol filters, gentamicin delivery was more rapid with ascending flow in both horizontal and vertical positions. Drug delivery was significantly delayed with descending flow in both positions. The Pall filter delivered gentamicin more rapidly in the horizontal position with either ascending or descending flow. The vertical filter position significantly delayed drug delivery in both flow directions. (804)

However, in another study, gentamicin sulfate 60 mg/15 mL was injected as a bolus through a 0.2-m nylon air-eliminating filter (Ultipor, Pall) to evaluate the effect of filtration on simulated intravenous push delivery. Enzyme-mediated assays showed that only about 38% of the drug was delivered through the filter after flushing with 10 mL of sodium chloride 0.9%. (809)

Filtration of 30 mL of a solution of gentamicin 500 g/mL (as the sulfate) (Schering) through Seitz sterilizing filters resulted in substantial binding of the drug to the filters. Losses ranged from 31 to 66%, depending on the filter size. (823) However, this filter medium does not

resemble current clinical filters. Subsequent reassay using membrane filters indicated little or no loss of activity. (829)

Thompson et al. evaluated gentamicin sulfate 5 and 10 mg/55 mL of dextrose 5% and sodium chloride 0.9% filtered over 20 minutes through a 0.22-m cellulose ester filter set (Ivex-2, Millipore). EMIT showed that virtually all of the drug was delivered through the filter. (1003)

Kane et al. evaluated the binding of gentamicin sulfate to the filter of a set used for continuous ambulatory peritoneal dialysis (CAPD). Gentamicin sulfate (Schering) 60 mg/2 L in Dianeal 137 with dextrose 4.25 and 1.5% was filtered through a Peridex CAPD filter set (Millipore); this set has a surface area 27 times larger than an inline intravenous filter. About 25% binding occurred from the solution containing dextrose 4.25%, but only 7.5% was bound with the 1.5% solution. (1112)

Gentamicin sulfate (Unicet-Unilabo) 0.32 mg/mL in dextrose 5% and sodium chloride 0.9% was filtered through a 0.22-m cellulose ester membrane filter (Ivex-HP, Millipore) over six hours. No significant drug loss due to binding to the filter was noted. (1034)

Central Venous Catheter Gentamicin sulfate (Fujisawa) 1 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. HPLC analysis was used to evaluate completeness of drug delivery through the catheter and the amount of chlorhexidine removed from the internal lumens. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter. (2335)



Gentamicin sulfateSolution Mfr Mfr Conc/L Remarks Ref C/IAmino acids 4.25%, dextrose 25%

MG SC 80 mg No increase in particulate matter in 24 hr at 5 C 349 C

Dextrose 4.3% in sodium chloride 0.18%

RS 160 mg Potency retained for up to 48 hr at room temperature 157 C

Dextrose 5% RS 160 mg Potency retained for up to 48 hr at room temperature 157 C

Dextrose 5% AB SC 160 mg Potency retained for 24 hr at 5 and 25 C 88 C

Dextrose 5% BAa, TR SC 1 g Potency retained for 24 hr at 5 and 22 C 298 C

Dextrose 5% BAb SC 1 g Potency retained for 30 days at -20 C 299 C

Dextrose 5% TRb SC 800 mg Physically compatible with little or no loss of potency in 24 hr at room temperature 554 C

Dextrose 5% 120 mg Physically compatible and gentamicin stable by microbiological assay for 24 hr at 25 C 897 C

Dextrose 5% ABb LY 1.2 gVisually compatible and potency by immunoassay retained for 48 hr at 25 C under fluorescent light and 4 C in the dark

1541 C

Dextrose 5% 600 mgFormation of decomposition products found by HPLC in 48 hr at room temperature. Gentamicin not quantified

2139 ?

Dextrose 10% SO SC60 mg/21.5 mLc

Visually compatible with no gentamicin loss by TDx in 30 days at 5 C in the dark 1731 C

Dextrose 10% SO SC120 mg/23 mLc

Visually compatible with no gentamicin loss by TDx in 30 days at 5 C in the dark 1731 C

Fat emulsion 10%, intravenous VT RS 160 mg Microscopic globule coalescence within 24 hr

at 8 and 25 C 825 I

Fructose 5% 120 mg Physically compatible and gentamicin stable by microbiological assay for 24 hr at 25 C 897 C

Mannitol 20% 120 mg Physically compatible and gentamicin stable by microbiological assay for 24 hr at 25 C 897 C

Ringer's injection 120 mg Physically compatible and gentamicin stable by microbiological assay for 24 hr at 25 C 897 C

Sodium chloride 0.9% 120 mg Physically compatible and gentamicin stable

by microbiological assay for 24 hr at 25 C 897 C

Sodium chloride 0.9% RS 160 mg Potency retained for up to 48 hr at room

temperature 157 C


BAa, TR SC 1 g Potency retained for 24 hr at 5 and 22 C 298 C

Sodium chloride 0.9% BAb SC 1 g Potency retained for 30 days at -20 C 299 C

Sodium chloride 0.9% ABb LY 1.2 g

Visually compatible and potency by immunoassay retained for 48 hr at 25 C under fluorescent light and 4 C in the dark

1541 C

Sodium chloride 0.9% ABd LY 800 mg Little or no loss of drug by HPLC in 24 hr at

25 C 1970 C

Sodium chloride 0.9% BAf APP 850 mg

Physically compatible with no increase in measured haze or particle content. About 4% gentamicin loss in 7 days at 23 C and 30 days at 4 C protected from light

2379 C

TPN #1, #4, #5, #7e SC 80 mg Physically compatible for 24 hr at 22 C 313 C

TPN #2, #3, #6, #8, #9e SC 80 mg Physically incompatible with precipitate noted

in 8 to 24 hr at 22 C 313 I

TPN #1e SC 80 mg Antibiotic potency retained for at least 12 hr at 313 C

22 C

TPN #10e SC 80 mg Physically compatible for 24 hr and antibiotic potency retained for at least 12 hr at 22 C 313 C

TPN #22e SC 800 mgPhysically compatible with no loss of activity by microbiological assay in 24 hr at 22 C in the dark

837 C

TPN #52 and TPN #53e SC 50 mg Physically compatible with no gentamicin loss

in 24 hr at 29 C by microbiological assay 440 C

TPN #107e 75 mgPhysically compatible and gentamicin activity retained for 24 hr at 21 C by microbiological assay

1326 C

aTested in both glass and PVC containers.


cTested in glass vials as a concentrate.

dTested in glass containers and latex elastomeric reservoirs (Secure Medical).

eRefer to Appendix I for the composition of parenteral nutrition solutions. TPN indicates a 2-in-1 admixture.

fTested in ethylene vinyl acetate (EVA) plastic AutoDose containers (Tandem Medical).


Gentamicin sulfateDrug Mfr Conc/L Mfr Conc/L Test Soln Remarks Ref C/IAmphotericin B 200 mg 320 mg D5W Haze develops over 3 hr 26 I

Ampicillin sodium BE 8 g RS 160 mg D5(1/4)S,

D5W, NS

50% gentamicin decomposition in 2 hr at room temperature

157 I

1 g 100 mg TPN #107a

42% gentamicin loss and 25% ampicillin loss in 24 hr at 21 C by microbiological assay

1326 I

Atracurium besylate BW 500 mg 2 g D5W

Physically compatible and atracurium chemically stable for 24 hr at 5 and 30 C

1694 C

Aztreonam SQ 10 and 20 g

SC 200 and 800 mg

D5W, NSb Little or no aztreonam loss in 48 hr at 25 C and 7 days at 4 C. Gentamicin potency retained for 12 hr at 25 C and 24 hr at 4 C, with up to

1023 C

10% loss in 48 hr at 25 C and 7 days at 4 C

Bleomycin sulfate BR 20 and

30 units SC50, 100, 300, 600 mg

NS

Physically compatible and bleomycin activity retained for 1 week at 4 C. Gentamicin not tested

763 C

Cefazolin sodium with clindamycin phosphate

SKF UP 10 g 9 g ES 800 mg D5Wc

10% cefazolin loss in 4 hr at 25 C. Clindamycin and gentamicin potency retained for 24 hr

1328 I

SKF UP 10 g 9 g ES 800 mg NSc

10% cefazolin loss in 12 hr at 25 C. Clindamycin and gentamicin potency retained for 24 hr

1328 I

Cefepime HCl BR 40 g ES 1.2 g D5W, NS Cloudiness forms in 18 hr at room temperature 1681 I

Cefotaxime sodium RS 50 mg SC 9 mg D5W

About 30% loss of gentamicin in 2 hr at 22 C by microbiological assay

504 I

RS 50 mg SC 6 mg D5WLess than 4% loss of gentamicin in 24 hr at 22 C by microbiological assay

504 C

Cefoxitin sodium MSD 5 g SC 400 mg D5S

4% cefoxitin decomposition in 24 hr and 11% in 48 hr at 25 C. 2% in 48 hr at 5 C. 9% gentamicin decomposition in 24 hr and 23% in 48 hr at 25 C. 2% in 48 hr at 5 C

308 C

Ceftazidime GLg 50 mg SC 6 and 9 mg D5W

10 to 20% loss of gentamicin in 2 hr at 22 C by microbiological assay

504 I

Ceftriaxone sodium RC 100 mg SC 9 mg D5W

13% loss of gentamicin in 8 hr at 22 C by microbiological assay

504 I

RC 100 mg SC 6 mg D5W5% loss of gentamicin in 24 hr at 22 C by microbiological assay

504 C

Cefuroxime sodium GL 7.5 g EX 800 mg D5W, NSb Physically compatible with

no loss of either drug in 1 hr 1036 C

1 g 100 mg TPN #107a

32% gentamicin loss in 24 hr at 21 C by microbiological assay

1326 I

Cimetidine HCl SKF 3 g SC 800 mg D5W Physically compatible and cimetidine chemically stable

551 C

for 24 hr at room temperature. Gentamicin not tested

SKF 1.2 and 5 g SC 80 mg D5W, NS

Physically compatible and cimetidine chemically stable for 24 hr at room temperature. Gentamicin not tested

551 C

Ciprofloxacin MI 1.6 g LY 1 g D5W, NS

Visually compatible and ciprofloxacin potency by HPLC and gentamicin potency by immunoassay retained for 48 hr at 25 C under fluorescent light and 4 C in the dark

1541 C

BAY 2 g SC 10 g NS

Visually compatible with little or no ciprofloxacin loss by HPLC in 24 hr at 25 C. Gentamicin not tested

1934 C

BAY 2 g SC 1.6 g D5W

Visually compatible with no loss of ciprofloxacin in 24 hr at 22 C under fluorescent light. Gentamicin not tested

2413 C

Clindamycin phosphate UP 1.2 g 60 mg D5W

Physically compatible. Clindamycin potency retained for 24 hr at room temperature

104 C

UP 2.4 g 120 mg D5W

Physically compatible. Clindamycin potency retained for 24 hr at room temperature

104 C

UP 9 g 800 mg D5W Clindamycin stability maintained for 24 hr 101 C

UP 12 g 600 mg D5W Physically compatible 101 C

UP 9 g AB 1 g D5W, NSd

Physically compatible and potency of both drugs retained for 48 hr at room temperature exposed to light and 1 week frozen

174 C

UP 9 g ES 1.2 g D5W, NScPhysically compatible and potency of both drugs retained for 28 days frozen

174 C

UP 9 g LY 1.2 g D5Wc Physically compatible and potency of both drugs retained for 7 days at 4 and

174 C

25 C

UP 18 g LY 2.4 g D5Wb

Physically compatible and potency of both drugs retained for 14 days at 4 and 25 C

174 C

UP 9 g LY 1.2 g NSc


174 C

UP 18 g LY 2.4 g NSb


174 C

UP 18 g ES 2.4 g D5W, NSbPotency of both drugs retained for 28 days frozen at -20 C

981 C

UP 6 g ES 667 mg D5Wb

Physically compatible with no clindamycin loss and 9% gentamicin loss in 24 hr at room temperature

995 C

400 mg 75 mg TPN #107a

19% gentamicin loss and 15% clindamycin loss in 24 hr at 21 C by microbiological assay

1326 I

Cloxacillin sodium BE 4 g RS 160 mg D5(1/4)S,

D5W, NS Precipitate forms 157 I

Cytarabine UP 100 mg 80 mg D5W Physically compatible for 24 hr 174 C

UP 300 mg 240 mg D5W Physically incompatible 174 I

Dopamine HCl AS 800 mg SC 2 g D5W

No dopamine decomposition and 7% gentamicin decomposition in 24 hr at 25 C

312 C

AS 800 mg SC 320 mg D5W

80% gentamicin decomposition in 24 hr at 23 to 25 C. Gentamicin potency retained for 6 hr. Dopamine potency retained for 24 hr

78 I

Floxacillin sodium BE 20 g RS 8 g NS Haze forms immediately and

precipitate forms in 2 hr 1479 I

BE 10 g EX 8 g NS

Physically compatible for 48 hr. Potency of both drugs retained when assayed after 1 hr at room temperature

1036 C

BE 10 g EX 8 g D5W Immediate precipitation 1036 I

Fluconazole PF 1 g SO 0.5 g D5W

Visually compatible with no fluconazole loss by HPLC in 72 hr at 25 C under fluorescent light. Gentamicin not tested

1677 C

Furosemide HO 800 mg SC 1.6 g D5W, NS Immediate precipitation of furosemide 876 I

HO 1 g RS 8 g NS

Physically compatible for 24 hr at 15 to 30 C. Slight precipitate forms in 48 to 72 hr

1479 C

Fusidate sodium LEO 1 g 160 mg D-SPhysically compatible and chemically stable for 48 hr at room temperature

1800 C

LEO 1 g 1.5 g D-S Physically incompatible 1800 I

Heparin sodium BP 20,000 units 320 mg D5W, NS Immediate precipitation 26 I

OR 20,000 units SC 1 g D5W, NS Opalescence 113 I

BRN1000 to 6000 units

ME 88 mg D10W, NS

Activity of both drugs by biological assays greatly reduced

1570 I

Linezolid PHU 2 g AB 800 mg f

Physically compatible with little or no linezolid loss by HPLC in 7 days at 4 and 23 C protected from light. Gentamicin losses of about 5 to 7% occurred in 7 days at 4 C and losses of about 8% occurred in 5 days at 23 C

2332 C

Meropenem ZEN 1 and 20 g SC 800 mg NS Visually compatible for 4 hr

at room temperature 1994 C

Metronidazole RP 5 ge RS 800 mg Physically compatible with little or no pH change for at least 72 hr at 23 C

807 C

5 g EX 800 mg D5W, NSb Physically compatible with no loss of either drug in 1 hr 1036 C

SE 5 g SC800 mg and 1.2 g

Physically compatible with no loss of either drug in 2 days at 18 C. At 4 C, no metronidazole loss but up to 10% gentamicin loss in 7 days

1242 C

RP 5 g 800 mg Visually compatible with no loss of metronidazole by

1931 C

HPLC in 15 days at 5 and 25 C. 10% gentamicin loss by immunoassay in 63 hr at 25 C and 10.6 days at 5 C

Midazolam HCl RC 50, 250, 400 mg EX 800 mg NS Visually compatible for 4 hr 355 C

Nafcillin sodium 1 g 75 mg TPN #107a

10% gentamicin loss in 24 hr at 21 C by microbiological assay

1326 I

Ofloxacin HO 2 g EX 800 mg WVisually compatible with little or no loss of either drug by HPLC in 48 hr

1613 C

Penicillin G sodium GL

13 and 40 million units

RS 160 mg D5(1/4)S, D5W, NS

Gentamicin potency retained for 24 hr at room temperature

157 C

Ranitidine HCl GL 100 mg 160 mg D5WPhysically compatible for 24 hr at ambient temperature under fluorescent light

1151 C

GL 50 mg and 2 g 80 mg D5W, NS

Physically compatible and ranitidine chemically stable by HPLC for 24 hr at 25 C. Gentamicin not tested

1515 C

Verapamil HCl KN 80 mg SC 160 mg D5W, NS Physically compatible for 24 hr 764 C

aRefer to Appendix I for the composition of parenteral nutrition solutions. TPN indicates a 2-in-1 admixture.


cTested in glass containers.

dTested in both glass and PVC containers.

eMinibags (100 mL) containing metronidazole 500 mg with disodium phosphate 150 mg, citric acid 44 mg, and sodium chloride 740 mg. This product differs from the Searle product.

fAdmixed in the linezolid infusion container.

gSodium carbonate-containing formulation tested.


Gentamicin sulfate

Drug (in syringe) Mfr Amt Mfr Amt Remarks Ref C/I

Ampicillin sodium AY 500 mg 80 mg/2 mL

Physically incompatible within 1 hr at room temperature 99 I

Caffeine citrate 20 mg/1 mL ES

10 mg/1 mL


Clindamycin phosphate UP 900 mg/6 mL ES

120 mg/4 mLa

Physically compatible with little or no loss of either drug for 48 hr at 25 C in polypropylene syringes

1159 C

Cloxacillin sodium BE 250 mg 80 mg/2 mL

Physically incompatible within 1 hr at room temperature 99 I

Diatrizoate meglumine 52%, diatrizoate sodium 8%

SQ 5 mL SC0.8 mg/1 mL

Physically compatible for at least 2 hr 1438 C

Diatrizoate meglumine 60% MA 5 mL SC

0.8 mg/1 mL


Dimenhydrinate 10 mg/1 mL

10 mg/1 mL

Clear solution 2569 C

10 mg/1 mL

40 mg/1 mL

Clear solution 2569 C

Heparin sodium 2500 units/1 mL

40 mg Turbidity or precipitate forms within 5 min 1053 I

Iohexol WI 64.7%, 5 mL SC

0.8 mg/1 mL


Iopamidol SQ 61%, 5 mL SC

0.8 mg/1 mL


Iothalamate meglumine 60% MA 5 mL SC

0.8 mg/1 mL


Ioxaglate meglumine 39.3%, ioxaglate sodium 19.6%

MA 5 mL SC0.8 mg/1 mL

Transient precipitate clears within 5 min 1438 ?

Pantoprazole sodium 4 mg/1 mL

40 mg/1 mL

Whitish precipitate 2574 I

Penicillin G sodium 1 million units

80 mg/2

No precipitate or color change within 1 hr at room temperature

99 C

mL

aDiluted to 4 mL with 1 mL of sodium chloride 0.9%.


Gentamicin sulfateDrug Mfr Conc Mfr Conc Remarks Ref C/I

Acyclovir sodium BW 5 mg/mLa TR 1.6 mg/mLa

Physically compatible for 4 hr at 25 C under fluorescent light

1157 C

Aldesleukin RCs 4800 I.U./mLb ES 40

mg/mL

Visually compatible and IL-2 activity by bioassay retained. Gentamicin not tested

1552 C

Allopurinol sodium BW 3 mg/mLb ES 5 mg/mLb Hazy solution with crystals forms in 1 hr 1686 I

Amifostine USB 10 mg/mLa ES 5 mg/mLa


1845 C

Amiodarone HCl LZ 4 mg/mLc LY 0.8 mg/mLc

Physically compatible for 4 hr at room temperature 1444 C

WY 6 mg/mLa APP 5 mg/mLa Visually compatible for 24 hr at 22 C 2352 C


SEQ 0.83 mg/mLa FUJ 5 mg/mLa Gross precipitate forms 2117 I

Amsacrine NCI 1 mg/mLa SO 5 mg/mLaPhysically compatible for 4 hr at room temperature under fluorescent light

1381 C

Anidulafungin VIC 0.5 mg/mLa AB 5 mg/mLa


2617 C

Atracurium besylate BW 0.5 mg/mLa ES 2 mg/mLa Physically compatible for 24 hr at 28 C 1337 C

Azithromycin PF 2 mg/mLb AMR 21 mg/mLep

Whitish-yellow microcrystals found upon filter inspection

2368 I

Aztreonam SQ 40 mg/mLa ES 5 mg/mLa Physically compatible with no subvisual haze or particle formation in 4 hr at

1758 C

23 C

Bivalirudin TMC 5 mg/mLa AB 5 mg/mLa


2373 C

Cefepime HCl BMS 120 mg/mLc 6 mg/mL

Physically compatible with less than 10% cefepime loss. Gentamicin not tested

2513 C

Ceftazidime SKBq 125 mg/mL 0.6 mg/mL

Visually compatible with less than 10% loss of both drugs in 1 hr

2434 C

GSKq 120 mg/mLg 6 mg/mL

Physically compatible with less than 10% ceftazidime loss. Gentamicin not tested

2513 C

Ciprofloxacin MI 2 mg/mLc LY 1.6 mg/mLc


Cisatracurium besylate GW 0.1, 2, 5 mg/mLa ES 5 mg/mLa


2074 C

Clarithromycin AB 4 mg/mLa RS 40 mg/mL

Visually compatible for 72 hr at both 30 and 17 C 2174 C

Cyclophosphamide MJ 20 mg/mLa TR 1.6 mg/mLa

Physically compatible for 4 hr at 25 C 1194 C

Cytarabine UP 16 mg/mLb GNS 15 mg/mLe

Visually compatible for 24 hr at room temperature in test tubes. No precipitate found on filter from Y-site delivery

2063 C

Daptomycin CUB 19.2 mg/mLbr AB 1.5

mg/mLr

Physically compatible with no loss of either drug by HPLC in 2 hr at 25 C

2553 C

Dexmedetomidine HCl AB 4 g/mLb APP 5 mg/mLb


2383 C

Diltiazem HCl MMD 1b and 5 mg/mL SCH

2.4b and 40 mg/mL

Visually compatible 1807 C

Docetaxel RPR 0.9 mg/mLa AB 5 mg/mLa Physically compatible with no change in measured turbidity or increase in

2224 C

particle content in 4 hr at 23 C

Doxapram HCl RB 2 mg/mLa APP 10 mg/mLa


Doxorubicin HCl liposome injection SEQ 0.4 mg/mLa ES 5 mg/mLa


2087 C

Drotrecogin alfa (activated) LI 0.1 and 1

mg/mLb AB 5 mg/mLb Strands form within 30 min 2615 I

Enalaprilat MSD 0.05 mg/mLb ES 0.8

mg/mLa


1355 C

Esmolol HCl DCC 10 mg/mLa ES 0.8 mg/mLa


Etoposide phosphate BR 5 mg/mLa AB 5 mg/mLa


2218 C

Famotidine MSD 0.2 mg/mLa ES 0.8 mg/mLb

Physically compatible for 14 hr 1196 C

ME 2 mg/mLb 5 mg/mLa Visually compatible for 4 hr at 22 C 1936 C

Fenoldopam mesylate AB 80 g/mLb APP 5 mg/mLb


2467 C

Filgrastim AMG 30 g/mLa LY 5 mg/mLa


1687 C

AMG 40 g/mLa GNS 1.6 mg/mLa

Visually compatible with little or no loss of filgrastim activity by bioassay and gentamicin by immunoassay in 4 hr at 25 C

2060 C

AMG 10 g/mLf GNS 1.6 mg/mLa

23% loss of filgrastim activity by bioassay in 4 hr at 25 C. Little or no gentamicin loss by

2060 I

immunoassay

Fluconazole RR 2 mg/mL ES 4 mg/mL Physically compatible for 24 hr at 25 C 1407 C

Fludarabine phosphate BX 1 mg/mLa ES 5 mg/mLaPhysically compatible for 4 hr at room temperature under fluorescent light

1439 C

Foscarnet sodium AST 24 mg/mL ES 4 mg/mLPhysically compatible for 24 hr at room temperature under fluorescent light

1335 C

AST 24 mg/mL ES 2 mg/mLc

Physically compatible for 24 hr at 25 C under fluorescent light by visual and microscopic examination

1393 C

Furosemide HO 10 mg/mL SC 1.6 mg/mLc

White precipitate of furosemide forms immediately

876 I

Gemcitabine HCl LI 10 mg/mLb AB 5 mg/mLb


2226 C

Granisetron HCl SKB 1 mg/mL ES 1.5 mg/mLb

Physically compatible with little or no loss of either drug by HPLC in 4 hr at 22 C

1883 C

Heparin sodium ES 50 units/mLc ES 3.2

mg/mLc Immediate gross haze 1316 I

TR 50 units/mL TR 2 mg/mL Visually incompatible

within 4 hr at 25 C 1793 I


AB 6% SC 5 mg/mLa


2339 C

Hetastarch in sodium chloride 0.9% DCC 6% TR 0.8

mg/mLb

Immediate precipitation which disappeared after 1 hr at room temperature

1313 I

Hydromorphone HCl WY 0.2 mg/mLa TR 0.8 mg/mLa

Physically compatible for at least 4 hr at 25 C under fluorescent light

987 C

Idarubicin HCl AD 1 mg/mLb ES 3 mg/mLa Color changes immediately 1525 IIL-2 RC 4800

I.U./mLbES 40

mg/mLVisually compatible and IL-2 activity by bioassay retained. Gentamicin not

1552 C

tested

Indomethacin sodium trihydrate MSD 0.5 and 1

mg/mLa 1 mg/mLaWhite turbidity forms immediately and becomes white flakes in 1 hr

1550 I

Insulin LI 0.2 unit/mLb TR 1.2

mg/mLbPhysically compatible for 2 hr at 25 C 1395 C

Iodipamide meglumine SQ

White precipitate forms immediately downstream to Y-site when given into a set through which gentamicin was administered previously

324 I

Labetalol HCl SC 1 mg/mLa ES 0.8 mg/mLa


Levofloxacin OMN 5 mg/mLa ES 10 mg/mL


2233 C

Linezolid PHU 2 mg/mL FUJ 5 mg/mLa


2264 C

Lorazepam WY 0.33 mg/mLb CNF 3 mg/mL Visually compatible for 24

hr at 22 C 1855 C

Magnesium sulfate IX16.7, 33.3, 66.7, 100 mg/mLa

SC 0.8 mg/mLa

Physically compatible for at least 4 hr at 32 C 813 C

Melphalan HCl BW 0.1 mg/mLb LY 5 mg/mLb


1557 C

Meperidine HCl WY 10 mg/mLa TR 0.8 mg/mLa


987 C

WY 10 mg/mLb ES 1.2 and 2 mg/mLb


Meropenem ZEN 1 and 50 mg/mLb SC 4 mg/mLg Visually compatible for 4

hr at room temperature 1994 C

Midazolam HCl RC 1 mg/mLa ES 10 mg/mL


RC 5 mg/mL CNF 3 mg/mL Visually compatible for 24 hr at 22 C 1855 C

Milrinone lactate SS 0.2 mg/mLa APP 10 mg/mLa


Morphine sulfate WI 1 mg/mLa TR 0.8 mg/mLa


987 C

ES 1 mg/mLb ES 1.2 and 2 mg/mLb


Multivitamins USV 5 mL/La SC80 mg/100 mLa


Nicardipine HCl DCC 0.1 mg/mLa ES 0.8 mg/mLa

Visually compatible for 24 hr at room temperature 235 C

Ondansetron HCl GL 1 mg/mLb ES 5 mg/mLa Physically compatible for 4 hr at 22 C 1365 C

Paclitaxel NCI 1.2 mg/mLa ES 5 mg/mLaPhysically compatible with no change in measured turbidity in 4 hr at 22 C

1556 C

Pancuronium bromide ES 0.05 mg/mLa ES 2 mg/mLa Physically compatible for

24 hr at 28 C 1337 C

Pemetrexed disodium LI 20 mg/mLb AB 5 mg/mLa Gross white precipitate forms immediately 2564 I

Propofol ZEN 10 mg/mL ES 5 mg/mLa White precipitate forms immediately 2066 I


ES 5 mg/mLa


2075 C

Sargramostim IMM 10 g/mLb SO 5 mg/mLa Physically compatible for 4 hr at 22 C 1436 C

Tacrolimus FUJ 1 mg/mLb SCN 4 mg/mLa Visually compatible for 24 hr at 25 C 1630 C

Teniposide BR 0.1 mg/mLa LY 5 mg/mLa


1725 C

Theophylline TR 4 mg/mL TR 2 mg/mL Visually compatible for 6 hr at 25 C 1793 C

Thiotepa IMMh 1 mg/mLa ES 5 mg/mLa


1861 C

Tigecycline WY 1 mg/mLb 1.4 mg/mLb


TNA #73i 32.5 mLj SC 80 mg/50 mLa

Physically compatible for 4 hr at 25 C by visual

1008 C

observation

TNA #97 to #104i ES 40 mg/mL

Physically compatible and gentamicin content retained for 6 hr at 21 C by TDx

1324 C

TNA #218 to #226i AB, FUJ 5 mg/mLa


2215 C

TPN #54i 13 and 20 mg/mL

Physically compatible and gentamicin activity retained over 6 hr at 22 C by microbiological assay

1045 C

TPN #61i k IX12.5 mg/1.25 mLl

Physically compatible 1012 C

m IX 75 mg/1.9 mLl Physically compatible 1012 C

TPN #91i n IX 5 mgo Physically compatible 1170 C

TPN #189i DB 1 mg/mLb Visually compatible for 24 hr at 22 C 1767 C

TPN #203 and TPN #204i ES 10


TPN #212 to #215i AB 5 mg/mLa


2109 C

Vasopressin APP 0.2 unit/mLb APP 1.2

mg/mLeVisually and microscopically compatible 2641 C

Vecuronium bromide OR 0.1 mg/mLa ES 2 mg/mLa Physically compatible for 24 hr at 28 C 1337 C

Vinorelbine tartrate BW 1 mg/mLb ES 5 mg/mLb


1558 C

Vitamin B complex with C (Berocca-C 500)

RC 4 mL/La SC80 mg/100 mLa


Vitamin B complex with C (Berocca-C) RC 20 mL/La SC

80 mg/100 mLa


Warfarin sodium DU 2 mg/mLg SC 1.6 mg/mLa Haze forms immediately 2010 I

DME 2 mg/mLg SC 1.6 Haze forms immediately 2078 I

mg/mLa

Zidovudine BW 4 mg/mLa IMS 2 mg/mLa


1193 C




dTested in dextrose 5%, Ringer's injection, lactated, sodium chloride 0.45%, and sodium chloride 0.9%.

eTested in sodium chloride 0.45%.

fTested in dextrose 5% with albumin human 2 mg/mL.

gTested in sterile water for injection.

hLyophilized formulation tested.

iRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3-in-1 admixture, and TPN indicates a 2-in-1 admixture.

jA 32.5-mL sample of parenteral nutrition solution mixed with 50 mL of antibiotic solution.

kRun at 21 mL/hr.

lGiven over 30 minutes by syringe pump.

mRun at 94 mL/hr.

nRun at 10 mL/hr.

oGiven over one hour by syringe pump.

pInjected via Y-site into an administration set running azithromycin.

qSodium carbonate-containing formulation tested.

rFinal concentration after mixing.

sThe Roche product is a different form of IL-2 than the commercial product.


Infusion Solutions Gentamicin sulfate maintains potency for 24 hours at room temperature in the following solutions (227) :

Dextran 40 (Dextran 10% in dextrose 5%)

Dextrose 5%

Dextrose 10%

Isolyte E in dextrose 5%

Isolyte M in dextrose 5%

Isolyte P in dextrose 5%

Normosol M in dextrose 5%

Normosol R

Normosol R in dextrose 5%

Ringer's injection



Kern et al. evaluated serum concentrations of gentamicin sulfate following intermittent 15 to 30-minute administration as piggyback infusions in 50 mL of dextrose 5% or 50 mL of TPN #177 (see Appendix I). Gentamicin serum concentrations were equivalent using both administration methods. (1573)

Peritoneal Dialysis Solutions The activity of gentamicin 10 mg/L was evaluated in peritoneal dialysis fluids containing 1.5 or 4.25% dextrose (Dianeal 137, Travenol). Storage at 25 C resulted in no loss of antimicrobial activity in 24 hours. (515)

Gentamicin sulfate (Schering) 3 and 10 mg/L in peritoneal dialysis concentrate with 50% dextrose (McGaw) retained about 90% of initial activity in seven hours and about 50 to 70% in 24 hours at room temperature as determined by microbiological assay. (1044)

The stability of gentamicin sulfate 8 mg/L, alone and with cefazolin sodium 75 and 150 mg/L, was evaluated in a peritoneal dialysis solution of dextrose 1.5% with heparin sodium 1000 units/L. Gentamicin activity was retained for 48 hours at both 4 and 26 C, alone and with both concentrations of cefazolin. Cefazolin activity was also retained over the study period. At 37 C, gentamicin losses ranged from 4 to 8% and cefazolin losses ranged from 10 to 12% in 48 hours. (1029)

In another study, the stability of gentamicin sulfate (Schering) was evaluated in peritoneal dialysate concentrates containing dextrose 30 and 50% (Dianeal) as well as in a diluted solution containing dextrose 2.5%. The gentamicin sulfate concentrations were 100 and 160 mg/L in the peritoneal dialysate concentrates and 5 and 8 mg/L in the diluted solutions. By immunoassay techniques, gentamicin sulfate was found to be stable in all of these solutions for at least 24 hours at 23 C. (1229)

Halstead et al. evaluated gentamicin 4 g/mL in Dianeal PDS with dextrose 1.5 and 4.25% (Travenol) with cefazolin 125 g/mL, heparin 500 units, and albumin human 80 mg in 2-L bags. The gentamicin content, determined by EMIT assay, was retained for 72 hours. (1413)

Drake et al. evaluated the retention of antimicrobial activity, using a disc diffusion bioassay, of gentamicin sulfate (SoloPak) 120 mg/L alone and with vancomycin hydrochloride (Lilly) 1 g/L in Dianeal PD-2 (Travenol) with dextrose 1.5%. Little or no loss of either antibiotic occurred in eight hours at 37 C. Gentamicin sulfate alone retained activity for at least 48 hours at 4 and 25 C. In combination with vancomycin hydrochloride, antimicrobial activity of both antibiotics was retained for up to 48 hours. However, the authors recommended refrigeration at 4 C for storage periods greater than 24 hours. (1414)

Gentamicin sulfate (American Pharmaceutical Partners) 8 mcg/mL in Delflex peritoneal dialysis solution bags with 2.5% dextrose (Fresenius) is stable by immunoassay with little or no loss occurring in 14 days refrigerated and at room temperature. (2573)

Gentamicin sulfate (American Pharmaceutical Partners) 8 mcg/mL with vancomycin hydrochloride (Lederle) 25 mcg/mL in Delflex peritoneal dialysis solution bags with 2.5% dextrose (Fresenius) is stable by immunoassay with little or no loss of either drug occurring in 14 days refrigerated and at room temperature. (2573)

-Lactam Antibiotics In common with other aminoglycoside antibiotics, gentamicin activity may be impaired by -lactam antibiotics. The inactivation is dependent on concentration, temperature, and time of exposure.

In 1971, McLaughlin and Reeves first reported the inactivation of gentamicin sulfate by carbenicillin disodium. They cited two cases in which gentamicin serum levels fell when carbenicillin was subsequently added to the regimen. They further noted a decrease in gentamicin half-life in serum, distilled water, and phosphate buffer to 40 hours at 35 C and 70 hours at 20 C. Gentamicin alone showed no loss of activity in 140 hours under these conditions. (219) Because the combined use of carbenicillin disodium and gentamicin sulfate has been reported to be additive or synergistic in its antibacterial effect against Pseudomonas and the combination has been used extensively in the clinical treatment of Pseudomonas infections, this article provoked quite a response in the literature.

Klastersky was not convinced of the result, citing the possibility that the antibacterial properties of gentamicin might have been inhibited by some other substance. It was further stated that given the success of combination therapy, even if such inhibition did occur, its clinical significance was not great. (220)

Levison and Kaye were not convinced either. Their tests of carbenicillin and gentamicin in serum and trypticase soy broth did not show loss of gentamicin in 18 hours at 37 C. (221)

Eykyn et al., however, did note slow inactivation of gentamicin by carbenicillin in vitro after several hours at 37 C. (222)

Furthermore, Riff and Jackson reported that gentamicin was biologically not detectable after prolonged mixture in solution with carbenicillin. They stated that gentamicin loses potency in proportion to time, temperature, and the concentration of carbenicillin. (223)

McLaughlin and Reeves combined, in vitro, 5 g/mL of gentamicin with carbenicillin concentrations of 250, 500, and 1000 g/mL. With incubation at 35 C, they detected no change in gentamicin at 250 g/mL of carbenicillin in eight hours; but in the 500-g/mL combination, a 44% loss of gentamicin was detected at eight hours. At 1000 g/mL of carbenicillin, 42 and 66% losses of gentamicin occurred in four and eight hours, respectively. (665)

Noone and Pattison evaluated the inactivation of gentamicin by various penicillins (and cephalosporins), including carbenicillin disodium. They noted a significant loss of gentamicin activity after 30 minutes and a 50% loss of potency after eight to 12 hours when gentamicin sulfate (Roussel) 160 mg/L was combined with carbenicillin disodium (Beecham) 20 g/L in various intravenous solutions at room temperature. (157)

Winters et al. confirmed that significant loss of gentamicin activity occurred in vitro when mixed with carbenicillin. Gentamicin in concentrations of 5 to 10 g/mL was mixed with a high concentration of carbenicillin, 500 g/mL. Within four to six hours at room temperature, significant loss of gentamicin activity had occurred. At lower concentrations, 50 to 100 g/mL, the loss of activity was much slower. Further experiments in dogs and humans showed that gentamicin serum levels were not significantly altered by concomitant carbenicillin therapy provided the two drugs were not mixed and allowed to stand before administration. (361)

In a similar in vitro experiment, Waitz et al. found the same result. Gentamicin activity dropped from 4.3 g/mL to 2.2 g/mL in 24 hours and to 1.4 g/mL in 72 hours at 20 C in the presence of carbenicillin 100 g/mL in distilled water. The amount of inactivation was dependent on temperature and time and was slowed by the addition of pH 7.0 buffers. Tests in mice and dogs failed to reveal any effect of carbenicillin on gentamicin serum levels. (362)

Zost and Yanchick failed to elucidate the situation further in their report since only the stability of carbenicillin disodium was reported (88), although they later said that the two antibiotics were stable for 24 hours. (224)

Riff and Jackson, however, found a 50% inactivation of gentamicin in four to six hours at room temperature when 24 g of carbenicillin disodium was added to 240 mg of gentamicin sulfate in sodium chloride 0.9%. They also noted that the half-life of gentamicin sulfate decreased as the ratio of carbenicillin disodium increased with respect to gentamicin sulfate in distilled water at 37 C. The authors stated that the inactivation of gentamicin by carbenicillin is dependent on the integrity of the -lactam ring, with carbenicillin and gentamicin interacting to form a conjugate inactivating both. The higher the concentration of carbenicillin, the faster is the inactivation of

gentamicin. Further, the rate of gentamicin inactivation is decreased by the presence of other solutes, especially proteins. (218)

Young et al. determined the degree of gentamicin loss in vitro for combinations of gentamicin plus carbenicillin of 400 g/mL plus 12.8 mg/mL, 40 g/mL plus 1.28 mg/mL, and 4 g/mL plus 0.128 mg/mL in distilled water. The solutions were incubated at 35 and 39 C. Gentamicin levels fell to 35 to 47% of initial amounts in eight hours at 35 C while the carbenicillin concentration was about 84 to 91% of the initial amount. At 39 C after eight hours, gentamicin levels of 12 to 24% and carbenicillin levels of 65 to 68% were determined. (666)

In vitro studies by Ervin et al. showed extensive decomposition of gentamicin by carbenicillin at 37 C in human serum. (363)

Similar inactivation effects on gentamicin sulfate occur in combination with ticarcillin (363) (365) (614), although the extent of inactivation appears to be less than with carbenicillin. (574) (575)

Holt et al. found that incubation of gentamicin sulfate 10 mg/L in sodium chloride 0.9% with 500 mg/L of carbenicillin or ticarcillin at 37 C for 24 hours resulted in about 60 to 70% reduction of gentamicin activity. When serum was substituted for the sodium chloride solution, 30 to 50% reduction in activity was reported. However, when buffered to pH 7.4 in aqueous solution, essentially all of the gentamicin activity was lost. (574)

Pickering and Gearhart reported that gentamicin sulfate 5 and 10 g/mL, dissolved in human serum and incubated with carbenicillin and ticarcillin 100 to 600 g/mL at 37 C, demonstrated greater rates of decomposition at the higher concentrations of the penicillins. In 24 hours, about a 9% loss of gentamicin activity occurred at 100 g/mL and about a 60% loss occurred at 600 g/mL of carbenicillin. Approximately a 20% loss at 100 g/mL and an 85% loss at 600 g/mL occurred in 72 hours with carbenicillin. Ticarcillin affected gentamicin less under these conditions. Little or no loss of gentamicin activity occurred at 100 g/mL of ticarcillin in 72 hours. However, the gentamicin loss increased to 20% at 300 g/mL and to 70% at 600 g/mL of ticarcillin in 72 hours. (575)

Murillo et al. determined that lower serum levels of gentamicin occurred in patients with normal renal function when concomitant ticarcillin disodium was administered compared to concomitant cephalothin sodium. The dose of ticarcillin disodium was 12 g/m2/day while cephalothin sodium was given at 7 g/m2/day. The gentamicin sulfate dose was 180 mg/m2/day. In one hour, gentamicin serum levels of 3.1 g/mL resulted in patients receiving the cephalothin while only 2.0 g/mL was achieved in patients on ticarcillin. Ticarcillin levels also were substantially reduced. (667)

Several aminoglycosides in combination with several penicillins were evaluated. Gentamicin sulfate, netilmicin sulfate, and tobramycin sulfate 5 g/mL were combined with carbenicillin disodium, azlocillin sodium, and mezlocillin sodium 50, 250, and 500 g/mL in human plasma. Samples were evaluated over nine days at 27 and 37 C. All of the aminoglycosides underwent significant inactivation during the evaluation. Aminoglycoside decomposition of 17 to 61% in 24 hours occurred at the higher two concentrations of penicillins-the highest inactivation was

sustained by tobramycin and the lowest by netilmicin. Little if any aminoglycoside inactivation occurred at 50 g/mL of penicillin. Carbenicillin caused greater aminoglycoside decomposition than did azlocillin or mezlocillin. (616)

Flournoy noted the relative degree of inactivation of tobramycin, gentamicin, netilmicin, and amikacin 10 mg/L in serum when combined with carbenicillin 125 to 1000 mg/L at -20 to 42 C. Tobramycin was more susceptible to inactivation than the others. Amikacin was the least susceptible, and gentamicin and netilmicin were similar in intermediate susceptibility to inactivation. (617)

Although piperacillin sodium and aminoglycosides act synergistically and have been used successfully clinically when recommended doses of each drug have been administered, mixing piperacillin sodium directly in a syringe or infusion bottle with an aminoglycoside can substantially inactivate the aminoglycoside. (740)

Hale et al. evaluated piperacillin and carbenicillin at concentrations of 62.5 to 1000 g/mL in human serum in combination with amikacin, gentamicin, or tobramycin 10 g/mL at 37 C for up to 24 hours by bioassay and radioimmunoassay. Penicillin concentrations of 62.5 and 125 g/mL had relatively little effect on the aminoglycoside concentration, even after 24 hours. However, increasing the penicillin concentration to 250 or 500 g/mL greatly increased decomposition. After 24 hours with carbenicillin 500 g/mL, the amounts of aminoglycosides remaining were amikacin, 82%; gentamicin, 43%; and tobramycin, 27%. After 24 hours with piperacillin 500 g/mL, the remaining concentrations were 95, 45, and 52%, respectively. Even greater inactivation occurred at 1000 g/mL of the penicillins, including the essentially complete loss of tobramycin in 24 hours. The authors concluded that amikacin is much more resistant to inactivation than the other aminoglycosides tested and that carbenicillin is apparently more aggressive in its inactivation than piperacillin. (816)

To determine if spurious aminoglycoside levels could result from a delay in assaying blood samples, Tindula et al. evaluated the inactivation of amikacin 35 g/mL and gentamicin and tobramycin 10 g/mL in human serum by 400-g/mL concentrations of several penicillins and cephalosporins. Samples were stored for 24 hours at room temperature and frozen at -20 C. For the room temperature samples, cefazolin caused relatively little inactivation. Nafcillin and cefoxitin caused moderate inactivation, 20% or less. Penicillin, ampicillin, carbenicillin, and ticarcillin generally caused 25% or more inactivation of gentamicin and tobramycin. Amikacin was somewhat less affected. Freezing samples at -20 C prevented significant inactivation of amikacin and gentamicin by any of the drugs. Freezing the tobramycin samples was satisfactory for most of the drugs except penicillin, ampicillin, and carbenicillin, which still exhibited a 15 to 20% tobramycin loss in 24 hours. (824)

Pickering and Rutherford evaluated several aminoglycosides combined with a number of penicillins. Gentamicin sulfate, netilmicin sulfate, and tobramycin sulfate 5 and 10 g/mL and amikacin 10 and 20 g/mL were combined in human serum with 125, 250, and 500 g/mL of azlocillin, carbenicillin disodium, amdinocillin, mezlocillin, and piperacillin individually. Tobramycin and gentamicin sustained greater losses than netilmicin and amikacin at each of the penicillin concentrations. Significant decomposition of all aminoglycosides occurred in 24 hours at 37 C at a penicillin concentration of 500 g/mL. Tobramycin and gentamicin had losses of 40

to 60%, while 15 to 30% losses occurred for netilmicin. Amikacin sustained the least inactivation with losses of about 10 to 20%. At penicillin concentrations of 125 to 250 g/mL, smaller losses of aminoglycosides were observed. (68)

The inactivation of gentamicin 10 g/mL in sterile distilled water by several -lactam antibiotics stored at 37 C was reported by Jorgensen and Crawford. Ticarcillin and carbenicillin 500 g/mL caused 34 and 44% gentamicin losses, respectively, in six hours, but only ticarcillin caused a significant loss (about 15%) at 100 g/mL. Cephalothin 500 g/mL caused a 17% gentamicin loss in four hours but no significant loss at 100 g/mL. Gentamicin was not inactivated by 500- or 100-g/mL concentrations of penicillin G, cefotaxime, or moxalactam. No loss of -lactam antibiotic activity was detected in any concentration. (973)

The comparative inactivation of five aminoglycosides by seven -lactam antibiotics in human serum at 37 C was reported by Riff and Thomason. Amikacin, followed by netilmicin, had the lowest degree of inactivation; tobramycin sustained the most pronounced losses. Gentamicin and kanamycin were intermediate in the extent of losses. The six penicillins that were tested all produced aminoglycoside inactivation; the greatest extent of inactivation was caused by carbenicillin, ticarcillin, penicillin G, oxacillin, methicillin, and ampicillin, in approximate descending order. Cephalothin produced minimal inactivation (5 to 10% in 24 hours). The rate of inactivation could be reduced by storage at 4 C and further reduced by storage at -20 C. The authors suggested processing blood samples rapidly to avoid inaccurate serum determinations. Storage of specimens at low temperature until analysis may be helpful. (1052)

Townsend reported the apparent inactivation of gentamicin sulfate by ampicillin sodium in blood samples held for 12 hours prior to assay. (1382)

Gentamicin sulfate (Schering) 25 g/mL combined separately with the cephalosporins cefazolin sodium (Lilly) and cefoxitin (MSD) at a concentration of 125 g/mL in peritoneal dialysis solution (Dianeal 1.5%) exhibited enhanced rates of lethality to Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa compared to any of the drugs alone. (1623)

The inactivation of gentamicin, tobramycin, and amikacin, each 5 g/mL, by seven -lactam antibiotics, 250 and 500 g/mL, in serum at 25 C over 24 hours was studied using bioassay, EMIT, fluorescence polarization immunoassay (TDx), and radioimmunoassay. No inactivation of any aminoglycoside by the cephalosporins moxalactam, cefotaxime, and cefazolin occurred within the study period. Results with the penicillins varied, depending on the assay technique used. The bioassay was the most sensitive to loss, TDx and radioimmunoassay were intermediate, and EMIT was the least sensitive. Azlocillin, carbenicillin, mezlocillin, and piperacillin all caused variable but extensive inactivation (up to 70%) of gentamicin and tobramycin in 24 hours. Amikacin, however, had only minor losses compared to the other aminoglycosides. (654)

The clinical significance of these interactions in patients appears to be primarily confined to those with renal failure. (218) (334) (361) (364) (616) (737) (816) (847) Literature reports of greatly reduced aminoglycoside levels in such patients have appeared frequently. (363) (365) (366) (367) (614) (666) (962) In addition, the interaction may be clinically important if assays

for aminoglycoside levels in serum are sufficiently delayed. (576) (618) (735) (832) (847) (1052) (1382)

Most authors believe that in vitro mixing of penicillins such as ticarcillin disodium with aminoglycoside antibiotics should be avoided but that clinical use of the drugs in combination can be of great value. It is generally recommended that the drugs be given separately in such combined therapy. (157) (218) (222) (224) (361) (364) (368) (369) (370)

Cephalosporins Cefotaxime (Hoechst-Roussel) should not be mixed with aminoglycosides in the same solution, but they may be administered to the same patient separately. (2) (792)

Cefotetan disodium is stated to be physically incompatible with aminoglycosides. (4) (283)

When gentamicin sulfate (Schering) 80 mg/100 mL in dextrose 5% was run through an administration set previously used to administer cefoperazone (Roerig) 1 g/100 mL in dextrose 5%, an immediate precipitate formed in the infusion tubing where the two solutions mixed. (831)

The in vivo activity of gentamicin sulfate with the cephalosporins, cefotaxime, ceftazidime, ceftriaxone sodium, and moxalactam disodium was evaluated in volunteers. Statistically significant reduction in aminoglycoside blood levels using a microbiological assay was found in the gentamicin sulfate-ceftriaxone sodium combination in the first hour postdose, but all other gentamicin sulfate combination differences were not statistically significant. (504)

(Also see the section on -Lactam Antibiotics.)

Local Anesthetics Gentamicin sulfate 80 mg (2 mL) was physically compatible with 1 mL of each of the following local anesthetics and did not show significant loss of potency in 24 hours at room temperature or under refrigeration (227) :

Chloroprocaine hydrochloride 1 and 2% (Pennwalt)

Lidocaine hydrochloride 1 and 2% (Astra)

Lidocaine hydrochloride 1 and 2% with epinephrine 1:100,000 (Astra)

Mepivacaine hydrochloride 1 and 2% (Winthrop)

Procaine hydrochloride 1 and 2% (Winthrop)

Heparin Addition of gentamicin sulfate (Roussel) 80 mg to the tubing of an infusion solution of sodium chloride 0.9% containing heparin resulted in immediate precipitation. (528)

Gentamicin sulfate 10 mg/L with heparin sodium 1000 units/L in Dianeal with dextrose 5% peritoneal dialysis solution was reported to be conditionally compatible. Koup and Gerbracht reported no significant reduction in gentamicin sulfate concentration or in the UV absorbance of heparin sodium in four to six hours. (228) However, a clarifying communication noted a marked reduction in the anticoagulant activity of heparin sodium if opalescence or a precipitate formed (which results if the undiluted drugs are combined), even if the precipitate redissolved. Heparin

activity was retained if one drug was added to a dilute solution of the other and no precipitate formed. (295)

The incompatibility of heparin sodium with gentamicin sulfate is said to result from coprecipitation. (230)

A white precipitate may result from the administration of gentamicin sulfate through a heparinized intravenous cannula. (976) Flushing heparin locks with sodium chloride 0.9% before and after administering drugs incompatible with heparin has been recommended. (4)

Phenytoin and Furosemide A 2-mL fluid barrier of dextrose 5% in a microbore retrograde infusion set failed to prevent precipitation when used between gentamicin sulfate 5 mg/0.5 mL and phenytoin sodium 5 mg/0.1 mL or furosemide 2 mg/0.2 mL. (1385)

Sodium Citrate The physical stability of gentamicin sulfate (Schering) 1, 2, and 5 mg/mL in sodium citrate 4% anticoagulant solution (Baxter) was evaluated. The combination has been used in preventing hemodialysis catheter-related infections. The gentamicin dilutions were packaged in 3-mL syringes and were stored at 4 and 23 C. The solutions were evaluated visually for color and clarity, and the pH was determined. The solutions remained clear and colorless for 35 days at both temperatures. The pH was found to be near 5.1 initially and did not change throughout the study. Although the gentamicin content was not measured, the authors pointed out that other studies had reported that the drug in solutions within the pH range of 4 to 7 was stable for up to 90 days. Furthermore, in another study, sodium citrate had also been documented to be stable for 28 days at room temperature. (2631)

Other Information

Heating Plasma Heating plasma samples to 56 C for one hour to inactivate potential HIV content resulted in no gentamicin loss as determined by TDx. (1615)

References




Or highlight and copy (Ctrl-C) the plain text citation below ............................................................LAWRENCE A. TRISSEL, F.A.S.H.P.. 2009. Handbook on Injectable Drugs. Bethesda, MD. American Society of Health-System Pharmacists. ISBN-13: 978-1-58528-213-5. STAT!Ref


Online Electronic Medical Library. http://online.statref.com/document.aspx?fxid=141&docid=169. 8/21/2010 3:01:19 AM CDT (UTC -05:00).




ISBN: o ISBN-13: 978-1-58528-213-5









"G" Monographs Gentamicin Sulfate - AHFS 8:12.02


Imipenem-Cilastatin Sodium - AHFS 8:12.07.08

Products Imipenem-cilastatin sodium for intravenous use is available as a fixed combination of equal quantities of both drugs. The combination is provided in vials and infusion bottles containing 250 and 500 mg of each drug with sodium bicarbonate 10 and 20 mg, respectively. (1-7/06)

The vials should be reconstituted with about 10 mL of a compatible diluent from a 100-mL infusion container and shaken well to form a suspension. Diluents containing benzyl alcohol should not be used to reconstitute the drug for use in neonates and small pediatric patients. The suspension must be transferred to the remaining solution in the infusion container for dilution. The suspension is not for direct injection. The procedure is then repeated: a 10-mL aliquot from the admixture is added to the vial and, once again, returned to the infusion admixture. This procedure ensures that all of the vial contents are transferred. The admixture should be agitated until it is clear to yield either a 2.5- or 5-mg/mL concentration, depending on the vial content. The admixture should not be heated to aid dissolution. (1-7/06) (4)

ADD-Vantage vials of imipenem-cilastatin sodium should be prepared with 100 mL of dextrose 5% or sodium chloride 0.9% in ADD-Vantage diluent bags. (1-7/06) (4)

The 250- and 500-mg piggyback infusion bottles should be reconstituted with 100 mL of compatible diluent and shaken until clear to yield 2.5- and 5-mg/mL concentrations, respectively. (1-7/06) (4)

Imipenem-cilastatin sodium for intramuscular use is available in vials containing 500 or 750 mg of each component. The vials should be reconstituted with 2 or 3 mL, respectively, of lidocaine hydrochloride 1% (without epinephrine) and agitated to form a suspension. This intramuscular formulation is not for intravenous use. (1-8/06) (4)

pH The intravenous product is buffered to pH 6.5 to 8.5. (1-7/06)

Osmolarity When reconstituted and diluted as directed by the manufacturer, the osmolarity of the intravenous admixture approximates that of the diluent. (4)

Sodium Content The 250- and 500-mg intravenous vials contain 0.8 mEq (18.8 mg) and 1.6 mEq (37.5 mg) of sodium, respectively. The 500- and 750-mg intramuscular vials contain 1.4 mEq (32 mg) and 2.1 mEq (48 mg) of sodium, respectively. (1-7/06) (1-8/06) (4)

Trade Name(s) Primaxin I.V., Primaxin I.M.

Administration Imipenem-cilastatin sodium for intravenous use is given by intermittent intravenous infusion, usually in sodium chloride 0.9%, at a concentration not exceeding 5 mg/mL. Infusion periods vary from 20 to 30 minutes up to 40 to 60 minutes, depending on the dose. The intramuscular formulation reconstituted as directed should be injected deeply into a large muscle mass. Suspensions of either formulation should not be given intravenously. (1-7/06) (1-8/06) (4)

/w EPDw ULLTE4N

Stability The sterile powder for injection should be stored below 25 C. (1-7/06) (1-8/06) (4)

Reconstituted as directed, intravenous solutions are colorless to yellow but may become a deeper yellow over time. Intramuscular suspensions are white to light tan. The manufacturer indicates that potency is not affected by color variations within this range (1-7/06) (1-8/06), but the solutions should be discarded if they darken to brown. (4) Intramuscular suspensions prepared with lidocaine hydrochloride (without epinephrine) should be used within one hour of preparation. (1-8/06) (4)

In solution, imipenem is substantially less stable than cilastatin and is the determining factor in the overall stability of the combination product. Reconstitution with most recommended infusion solutions (see Additional Compatibility Information) results in solutions that are stable for four hours at room temperature or 24 hours under refrigeration at 4 C. (1-7/06)

Imipenem degradation kinetics were determined for a 2.5-mg/mL solution in sodium chloride 0.9%. The degradation rates were temperature dependent, with a half-life of over 44 hours at 2 C dropping to six hours at 25 C and to two hours at 37 C. The decomposition was consistent with hydrolysis, and the loss of antimicrobial activity suggests cleavage of the -lactam ring. (1272)

The decomposition of imipenem as a 5-mg/mL solution in dextrose 5% in the presence of cilastatin was estimated to occur at a rate of about 1.4% per hour at room temperature. At this rate, the time to 10% decomposition will be reached in 6 to 7 hours. (2166)

pH Effects Imipenem is inactivated at acidic or alkaline pH but is more stable at neutral pH. (4) The pH range of maximum stability appears to be 6.5 to 7.5, with increasing rates of decomposition occurring as the pH moves away from this range. (1273) At a pH of about 4, the half-life of imipenem is about 35 minutes. (2166)

Freezing Solutions The manufacturer recommends that imipenem-cilastatin solutions not be frozen. (1-7/06) At concentrations of 250 and 500 mg/100 mL in sodium chloride 0.9%, imipenem losses of around 15% occurred in one week when frozen at -20 and -10 C. (1141) Freezing solutions at temperatures above -70 C offers no stability advantage over refrigerated storage (1141) and results in decomposition of imipenem in a manner similar to ampicillin. (4)

Effects of Solution Components Dextrose exerts an adverse effect on the stability of imipenem. Dextrose 5 and 10% reduced the time to 10% decomposition by about one-half compared to sterile water. Similarly, increasing mannitol concentrations reduce imipenem stability. Sodium chloride content increases imipenem stability because of a positive kinetic salt effect similar to other -lactam antibiotics. Both lactate and bicarbonate anions attack the -lactam ring and decrease imipenem stability. (1141) (See Additional Compatibility Information.)

Elastomeric Reservoir Pumps Imipenem-cilastatin sodium (Merck) 5 mg/mL in dextrose 5% and sodium chloride 0.9% 100 mL was packaged in latex elastomeric reservoirs (Secure Medical). Little or no loss by HPLC analysis occurred in 4 hours at 25 C and in 24 hr at 5 C. (1970)

Imipenem-cilastatin sodium (Merck) 5 mg/mL in both dextrose 5% and sodium chloride 0.9% was evaluated for binding potential to natural rubber elastomeric reservoirs (Baxter). Less than 1% binding was found after storage for two weeks at 35 C with gentle agitation. (2014)

Imipenem-cilastatin solutions in elastomeric reservoir pumps have been stated by the pump manufacturers to be stable for the following time periods refrigerated (REF) and at room temperature (RT) (31) :

Pump Reservoir(s) Conc. REF RTHomepump; Homepump Eclipse 5 mg/mLb 48 hr 10 hrMedflo 5 mg/mLa 24 hr 4 hr 5 mg/mLb 48 hr 10 hrReadyMed 5 mg/mLb 72 hr 24 hraIn dextrose 5%.bIn sodium chloride 0.9%.

Sorption Imipenem-cilastatin (MSD) 2.5 mg/mL in dextrose 5% and sodium chloride 0.9% packaged in PVC, polyethylene, and glass containers exhibited no loss due to sorption to any of the container types when stored at 4 and 22 C for 24 hours protected from light. (2289)

Central Venous Catheter Imipenem-cilastatin (MSD) 2 mg/mL in sodium chloride 0.9% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. HPLC analysis was used to evaluate completeness of drug delivery through the catheter and the amount of chlorhexidine removed from the internal lumens. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter. (2335)



Imipenem-cilastatin sodiumSolution Mfr Mfr Conc/L Remarks Ref C/IDextrose 5% with potassium chloride 0.15%

ABa MSD 2.5 g9% imipenem loss in 6 hr and 15% in 9 hr at 25 C. 8% loss in 48 hr and 14% in 72 hr at 4 C

1141 Ib

Dextrose 5% with potassium chloride 0.15%

ABa MSD 5 g8% imipenem loss in 3 hr and 15% in 6 hr at 25 C. 8% loss in 24 hr and 13% in 48 hr at 4 C

1141 Ib

Dextrose 5% in Ringer's injection, lactated


1141 I

Dextrose 5% in Ringer's injection, lactated

ABa MSD 5 g 14% imipenem loss in 3 hr at 25 C and 13% in 24 hr at 4 C 1141 I

Dextrose 5% with sodium bicarbonate 0.02%


1141 Ib

Dextrose 5% with sodium bicarbonate 0.02%


1141 Ib

Dextrose 5% in sodium chloride 0.225%

ABa MSD 2.5 g 8% imipenem loss in 6 hr and 12% in 9 hr at 25 C. 10% loss in 48 hr at 4 C 1141 Ib



1141 Ib



1141 Ib



1141 Ib



1141 Ib



1141 Ib

Dextrose 5% ABa MSD 2.5 g5% imipenem loss in 3 hr and 10% in 6 hr at 25 C. 8% loss in 24 hr and 14% in 48 hr at 4 C

1141 Ib

Dextrose 5% ABa MSD 5 g6% imipenem loss in 3 hr and 15% in 6 hr at 25 C. 8% loss in 24 hr and 14% in 48 hr at 4 C

1141 Ib

Dextrose 5% ABc ME 5 g Little or no loss of drug by HPLC in 4 hr at 25 C and in 24 hr at 5 C 1970 C

Dextrose 5% BA MSD 5 gVisually compatible with 10% imipenem loss by HPLC in about 6 hr at 23 C and in 48 hr at 4 C

2166 Ib

Dextrose 5% BAe, BRNf MSD 2.5 g Visually compatible with little or no loss by

HPLC in 24 hr at 4 and 22 C 2289 C

Dextrose 10% ABa MSD 2.5 g6% imipenem loss in 3 hr and 10% in 6 hr at 25 C. 8% loss in 24 hr and 13% in 48 hr at 4 C

1141 Ib

Dextrose 10% ABa MSD 5 g 8% imipenem loss in 3 hr and 13% in 6 hr at 25 C. 10% loss in 24 hr at 4 C 1141 Ib

Mannitol 2.5% ABa MSD 2.5 g 9% imipenem loss in 9 hr at 25 C. 7% loss in 1141 Ib

48 hr and 11% in 72 hr at 4 C

Mannitol 2.5% ABa MSD 5 g6% imipenem loss in 3 hr and 12% in 6 hr at 25 C. 7% loss in 24 hr and 10% in 48 hr at 4 C

1141 Ib

Mannitol 5% ABa MSD 2.5 g6% imipenem loss in 3 hr and 10% in 6 hr at 25 C. 9% loss in 48 hr and 13% in 72 hr at 4 C

1141 Ib

Mannitol 5% ABa MSD 5 g 7% imipenem loss in 3 hr and 12% in 6 hr at 25 C. 12% loss in 48 hr at 4 C 1141 Ib

Mannitol 10% ABa MSD 2.5 g6% imipenem loss in 3 hr and 10% in 6 hr at 25 C. 7% loss in 24 hr and 12% in 48 hr at 4 C

1141 Ib

Mannitol 10% ABa MSD 5 g 12% imipenem loss in 3 hr at 25 C. 13% loss in 48 hr at 4 C 1141 Ib

Normosol M in dextrose 5% ABa MSD 2.5 g

7% imipenem loss in 3 hr and 11% in 6 hr at 25 C. 9% loss in 24 hr and 19% in 48 hr at 4 C

1141 Ib

Normosol M in dextrose 5% ABa MSD 5 g 8% imipenem loss in 3 hr and 14% in 6 hr at

25 C. 10% loss in 24 hr at 4 C 1141 Ib

Ringer's injection, lactated ABa MSD 2.5 g


1141 I

Ringer's injection, lactated ABa MSD 5 g


1141 I

Sodium bicarbonate 5% ABa MSD 2.5 g 43% imipenem loss in 3 hr at 25 C. 52% loss

in 24 hr at 4 C 1141 I

Sodium bicarbonate 5% ABa MSD 5 g 45% imipenem loss in 3 hr at 25 C. 50% loss

in 24 hr at 4 C 1141 I

Sodium chloride 0.9% ABa MSD 2.5 g 6% imipenem loss in 9 hr at 25 C. 7% loss in

72 hr at 4 C 1141 Ib

Sodium chloride 0.9% ABa MSD 5 g 8% imipenem loss in 9 hr at 25 C. 7% loss in

48 hr and 11% in 72 hr at 4 C 1141 Ib

Sodium chloride 0.9% ABc ME 5 g Little or no loss of drug by HPLC in 4 hr at 25

C and in 24 hr at 5 C 1970 C


BAe, BRNf MSD 2.5 g Visually compatible with little or no loss by

HPLC in 24 hr at 4 and 22 C 2289 C

Sodium chloride 0.9% BAg APO 2.5 g

Yellow-brown color forms in 3 days at 23 C. About 7% loss in 8 hr and 15% loss in 24 hr at 23 C. About 7% loss in 3 days and 13% loss in 5 days at 4 C protected from light

2384 Ib

Sodium chloride 0.9% BAg APO 5 g

Yellow-brown color forms in 3 days at 23 C. About 8% loss in 8 hr and 12% loss in 24 hr at 23 C. About 5% loss in 3 days and 13% loss in 5 days at 4 C protected from light

2384 Ib

Sodium lactate (1/6) M ABa MSD 2.5 g 13% imipenem loss in 3 hr at 25 C. 8% loss in

24 hr and 15% in 48 hr at 4 C 1141 I

Sodium lactate (1/6) M ABa MSD 5 g 18% imipenem loss in 3 hr at 25 C. 14% loss

in 24 hr at 4 C 1141 I

TPN #107d 500 mg 57% imipenem loss in 24 hr at 21 C by microbiological assay 1326 I

TPN #241, #242d MSD 5 g 8 to 10% imipenem loss by HPLC within 30 min at 25 C under fluorescent light 493 I

aTested in glass containers.

bIncompatible by conventional standards but recommended for dilution of imipenem-cilastatin with use in shorter periods of time.

cTested in glass containers and latex elastomeric reservoirs (Secure Medical).

dRefer to Appendix I for the composition of parenteral nutrition solutions. TPN indicates a 2-in-1 admixture.

eTested in PVC containers.

fTested in polyethylene and glass containers.

gTested in ethylene vinyl acetate (EVA) AutoDose bags (Tandem Medical).


Imipenem-cilastatin sodiumDrug Mfr Conc Mfr Conc Remarks Ref C/I

Acyclovir sodium BW 5 mg/mLa MSD 5 mg/mLb Physically compatible for 4 hr at 25 C 1157 C

Allopurinol sodium BW 3 mg/mLb MSD 10

mg/mLb Haze and particles form in 1 hr 1686 I

Amifostine USB 10 mg/mLa MSD 10 mg/mLa


1845 C

Amiodarone HCl WY 6 mg/mLa ME 5 mg/mLa Immediate white haze. Became yellow in 24 hr 2352 I


SEQ 0.83 mg/mLa ME 10

mg/mLb Gross precipitate forms 2117 I

Anidulafungin VIC 0.5 mg/mLa

ME 5 mg/mLb Physically compatible with no change in measured turbidity or increase in particle content in 4

2617 C

hr at 23 C

Azithromycin PF 2 mg/mLb ME 5 mg/mLbg

Whitish-yellow microcrystals found upon filter inspection 2368 I

Aztreonam SQ 40 mg/mLa MSD 10 mg/mLa


1758 C

Cefepime HCl BMS 20 mg/mLa MSD 10 mg/mLa


1689 C

Cisatracurium besylate GW 0.1, 2, 5

mg/mLa ME 10 mg/mLb


2074 C

Diltiazem HCl MMD 5 mg/mL MSD 5 mg/mLc Visually compatible 1807 C

Docetaxel RPR 0.9 mg/mLa ME 10

mg/mLb


2224 C


mg/mLb ME 5 mg/mLb Strands form within 4 hr 2615 I

Etoposide phosphate BR 5 mg/mLa ME 10

mg/mLbYellow discoloration forms in 4 hr at 23 C 2218 I

Famotidine MSD 0.2 mg/mLa MSD 10

mg/mLb Physically compatible for 14 hr 1196 C

ME 2 mg/mLb 5 mg/mLb Visually compatible for 4 hr at 22 C 1936 C

Filgrastim AMG 30 g/mLa MSD 10 mg/mLa


1687 C

AMG 40 g/mLa ME 5 mg/mLa

16% loss of filgrastim activity by bioassay in 4 hr at 25 C. Little or no imipenem and cilastatin loss by HPLC

2060 I

AMG 10 g/mLd ME 5 mg/mLa

Visually compatible with little or no loss of filgrastim activity by bioassay and imipenem and cilastatin by HPLC in 4 hr at 25 C

2060 C

Fluconazole RR 2 mg/mL MSD 10 mg/mL Immediate precipitation 1407 I

Fludarabine phosphate BX 1 mg/mLa MSD 5 mg/mLa


1439 C

Foscarnet sodium AST 24 mg/mL MSD 10 mg/mL


1335 C

AST 24 mg/mL MSD 5 mg/mLa


1393 C

Gallium nitrate FUJ 1 mg/mLb MSD 5 mg/mLb Precipitates immediately 1673 I

Gemcitabine HCl LI 10 mg/mLb ME 10 mg/mLb

Yellow-green discoloration forms in 1 hr 2226 I

Granisetron HCl SKB 0.05 mg/mLa ME 10

mg/mLa


2000 C

Idarubicin HCl AD 1 mg/mLb MSD 5 mg/mLbVisually compatible for 12 hr at 25 C under fluorescent light. Precipitate forms in 24 hr

1525 C

Insulin, regular LI 0.2 unit/mLb MSD 4 and 5


Linezolid PHU 2 mg/mL ME 10 mg/mLb


2264 C

Lorazepam WY 0.33 mg/mLb MSD 5 mg/mL Yellow precipitate forms in 24

hr 1855 I

Melphalan HCl BW 0.1 mg/mLb MSD 10

mg/mLb


1557 C

Meperidine HCl AB 10 mg/mL MSD 5 mg/mLaYellow discoloration forms within 2 hr at 25 C under fluorescent light

1397 I

Methotrexate sodium 30 mg/mL MSD 5 mg/mL Visually compatible for 4 hr at

room temperature 1788 C

Midazolam HCl RC 5 mg/mL MSD 5 mg/mL Haze forms in 24 hr 1855 I

Milrinone lactate SS 0.2 mg/mLa ME 5 mg/mLb Yellow color darkening in 4 hr

at 25 C 2381 I

Ondansetron HCl GL 1 mg/mLb MSD 5 mg/mLb Physically compatible for 4 hr at 22 C 1365 C

Propofol ZEN 10 mg/mL ME 10 mg/mLb


2066 C

Remifentanil HCl GW 0.025 and 0.25 mg/mLb

ME 10 mg/mLa

Physically compatible with no change in measured turbidity or increase in particle content in 4

2075 C

hr at 23 C

Sargramostim IMM 10 g/mLb MSD 5 mg/mLb Large particle and fibrous clump form in 4 hr 1436 I

Sodium bicarbonate 1.4% 5 mg/mLa Pale yellow precipitate forms in

1 hr at room temperature 1788 I

Tacrolimus FUJ 1 mg/mLb MSD 10 mg/mLb


Teniposide BR 0.1 mg/mLa MSD 10

mg/mLb


1725 C

Thiotepa IMMe 1 mg/mLa ME 10 mg/mLa


1861 C

Tigecycline WY 1 mg/mLb 5 mg/mLb Physically compatible for 4 hr 2714 C

TNA #218 to #226f ME 10 mg/mLb


2215 C

TPN #212 to #215f ME 10 mg/mLb


2109 C

Vasopressin APP 0.2 unit/mLb ME 5 mg/mLa Visually and microscopically

compatible 2641 C

Vinorelbine tartrate BW 1 mg/mLb MSD 10

mg/mLb


1558 C

Zidovudine BW 4 mg/mLa MSD 5 mg/mLa


1193 C




dTested in dextrose 5% with albumin human 2 mg/mL.

eLyophilized formulation tested.

fRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3-in-1 admixture, and TPN indicates a 2-in-1 admixture.

gInjected via Y-site into an administration set running azithromycin.


Infusion Solutions The manufacturer recommends the following infusion solutions for the dilution of imipenem-cilastatin (1-7/06) :

Dextrose 5% with potassium chloride 0.15%

Dextrose 5% in sodium chloride 0.225, 0.45, and 0.9%

Dextrose 5 and 10%

Mannitol 5 and 10%


Imipenem-cilastatin is stated to be stable in these infusion solutions for four hours at room temperature or 24 hours when refrigerated at 5 C. (4)

The utility time, or time to 10% decomposition (t90), for imipenem-cilastatin in various infusion solutions has been determined. (1141) The results are presented in Table 1.

Table 1. Utility Time (t90) of Imipenem-Cilastatin in Infusion Solutions 1141 Time (hr) to 10% Decomposition 25 C 4 C

Infusion Solution 250 mg/100 mL

500 mg/100 mL

250 mg/100 mL

500 mg/100 mL

Dextrose 5% with potassium chloride 0.15% 6.3 4.2 51.4 35.4

Dextrose 5% in Ringer's injection, lactated 4.1 2.5 30.9 24.7

Dextrose 5% with sodium bicarbonate 0.02% 5.5 5.4 37.1 34.6

Dextrose 5% in sodium chloride 0.225% 7.3 5.4 52.9 36.7



Dextrose 5% 6.6 4.7 37.0 36.4Dextrose 10% 5.9 4.3 39.0 31.3Mannitol 2.5% 10.1 6.3 65.0 43.6Mannitol 5% 6.4 5.9 54.9 44.7Mannitol 10% 5.9 3.9 43.6 41.7

Normosol M in dextrose 5% 5.2 4.6 26.8 33.4Ringer's injection, lactated 6.8 5.4 47.4 41.9Sodium bicarbonate 5% 0.5 0.4 2.6 2.9Sodium chloride 0.9% 15.0 11.1 103.0 67.3Sodium lactate (1/6) M 2.2 1.9 33.6 19.3

Aminoglycosides The manufacturer recommends not physically combining imipenem-cilastatin with other anti-infectives such as aminoglycosides. However, the drugs may be administered from separate containers through the same tubing. (1-7/06) (1-8/06) (4)

Tobramycin The potential for inactivation of tobramycin sulfate by the carbapenem antibiotic imipenem-cilastatin sodium was investigated by Ariano et al. Tobramycin sulfate 10 g/mL was incubated at 37 C for five days with imipenem-cilastatin sodium at concentrations ranging from 10 to 40 g/mL in human serum. Degradation rates of tobramycin sulfate determined by fluorescence polarization immunoassay were not enhanced by the presence of imipenem-cilastatin sodium. (2013)

Tobramycin sulfate 10 g/mL was also evaluated for inactivation potential with aztreonam, ceftazidime, and imipenem, each at a concentration of 100 g/mL in water. Little or no loss of activity of any of the antibiotics was found in 24 hours at 37 C using HPLC (for the -lactam antibiotics) and an enzyme-mediated immunoassay technique (EMIT) for the tobramycin as well as microbiological plate assays. (498)

References









ISBN: o ISBN-13: 978-1-58528-213-5









"I" Monographs Imipenem-Cilastatin Sodium - AHFS 8:12.07.08


Metronidazole - AHFS 8:30.04

Products Metronidazole is available as a ready-to-use solution in 100-mL single-dose PVC plastic bags. No dilution or buffering is required. Each bag contains (1-4/06) :

Metronidazole 500 mg

/w EPDw ULLTE4N

Dibasic sodium phosphate 48 mgCitric acid anhydrous 23 mgSodium chloride 790 mgWater for injection qs 100 mL

pH Metronidazole ready-to-use has a pH of 5.8 (range 4.5 to 7). (1-4/06) (17)

Osmolarity Metronidazole ready-to-use has an osmolarity of 314 mOsm/L. (1-4/06)

Sodium Content Metronidazole ready-to-use contains 14 mEq of sodium from the excipients per 500 mg of metronidazole. (1-4/06) (4)

Trade Name(s) Flagyl I.V. RTU

Administration Metronidazole ready-to-use is administered by continuous intravenous infusion or by intermittent intravenous infusion over one hour. Metronidazole ready-to-use may be administered without dilution or buffering. (1-4/06) (4)

Stability Metronidazole ready-to-use is a clear, colorless solution which should be stored at controlled room temperature and protected from light. (1-4/06) (4) It should not be stored under refrigeration. (1-4/06) Refrigeration may result in crystal formation. However, the crystals redissolve on warming to room temperature. (1115)

Light Effects Prolonged exposure to light will cause a darkening of the product. (4) However, most manufacturers indicate that short-term exposure to normal room light does not adversely affect metronidazole stability. Direct sunlight should be avoided. (1115)

Elastomeric Reservoir Pumps Metronidazole 5 mg/mL in Homepump and Homepump Eclipse elastomeric reservoir pumps has been stated by the pump manufacturer to be stable for 24 hours at room temperature and 10 days under refrigeration, although precipitation may occur during refrigerated storage. (31)

Sorption Metronidazole (May Baker) 30 mg/L in sodium chloride 0.9% (Travenol) in PVC bags did not exhibit significant sorption to the plastic during one week of storage at room temperature (15 to 20 C). (536)

In another study, metronidazole (May Baker) 30 mg/L in sodium chloride 0.9% did not exhibit any loss due to sorption during a seven-hour simulated infusion through an infusion set (Travenol) consisting of a cellulose propionate burette chamber and 170 cm of PVC tubing. (606)

The drug was also tested as a simulated infusion over at least one hour by a syringe pump system. A glass syringe on a syringe pump was fitted with 20 cm of polyethylene tubing or 50 cm of Silastic tubing. No loss of drug due to sorption was observed with either tubing. (606)

A 25-mL aliquot of metronidazole (May Baker) 30 mg/L in sodium chloride 0.9% was stored in all-plastic syringes composed of polypropylene barrels and polyethylene plungers for 24 hours at room temperature in the dark. No loss due to sorption occurred. (606)

Filtration Metronidazole (Specia) 5 mg/mL in dextrose 5% and sodium chloride 0.9% was filtered through a 0.22-m cellulose ester membrane filter (Ivex-HP, Millipore) over six hours. No significant drug loss due to binding to the filter was noted. (1034)

Central Venous Catheter Metronidazole (Baxter) 5 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. HPLC analysis was used to evaluate completeness of drug delivery through the catheter and the amount of chlorhexidine removed from the internal lumens. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter. (2335)



Metronidazole


Amikacin sulfate BR 5 g RP 5 ga Physically compatible with little or no pH change for at least 12 hr at 23 C

807 C

Amoxicillin sodium-clavulanate potassium

BE 20 + 2 g BAY 5 g

Physically compatible with 8% clavulanate loss in 2 hr and 25% loss in 6 hr at 21 C by HPLC. 7 to 8% amoxicillin and no metronidazole loss in 6 hr at 21 C

1920 I

Ampicillin sodium AY 20 g RP 5 ga Physically compatible for at least 72 hr at 23 C, but pH changed significantly

807 ?

BR 20 g SE 5 g 9% ampicillin loss in 22 hr at 25 C and 12 days at 5 C. No metronidazole loss

993 C

Aztreonam SQ 10 and 20 g MG 5 g

Pink color develops in 12 hr, becoming cherry red in 48 hr at 25 C. Pink color develops in 3 days at 4 C. No loss of either drug detected

1023 I

Cefazolin sodium LI 10 g RP 5 ga Physically compatible with little or no pH change for at least 24 hr at 23 C and 72 hr at

807 C

4 C

LI 10 g SE 5 g

5% cefazolin loss and no metronidazole loss in 7 days at 25 C. No loss of either drug in 12 days at 5 C

993 C

LI 10 g AB 5 g Visually compatible with no loss of either drug by HPLC in 72 hr at 8 C

1649 C

Cefepime HCl BR 40 gAB, ES, SE

5 g

4% cefepime loss by HPLC in 24 hr at room temperature exposed to light and 10% loss in 7 days at 5 C. Little or no metronidazole loss by HPLC. However, orange color develops in 18 hr at room temperature and 24 hr at 5 C

1682 ?

BR 4 gAB, ES, SE

5 g

5% cefepime loss by HPLC in 24 hr at room temperature exposed to light and 3% loss in 5 days at 5 C. Little or no metronidazole loss by HPLC. However, orange color develops in 18 hr at room temperature and 24 hr at 5 C

1682 ?

BMS 20 g SCS 5 g b

Visually compatible. HPLC found 7% cefepime loss in 48 hr and 11% loss in 72 hr at 23 C; 8% cefepime loss in 7 days at 4 C. No metronidazole loss in 7 days at 4 and 23 C

2324 C

BMS 10 g SCS 5 g b

Visually compatible. HPLC found 9% cefepime loss in 72 hr at 23 C and 4% or less loss in 7 days at 4 C. 7% or less metronidazole loss in 7 days at 4 and 23 C

2324 C

BMS 5 g SCS 5 g b

Visually compatible. HPLC found 9% cefepime loss in 48 hr at 23 C and 2% or less loss in 7 days at 4 C. Little or no metronidazole loss in 7 days at 4 and 23 C

2324 C

BMS 2.5 g SCS 5 g b Visually compatible. HPLC found 8% cefepime loss in 48 hr and 12% loss in 72 hr at 23

2324 C

C; 7% cefepime loss in 7 days at 4 C. 5% or less metronidazole loss in 7 days at 4 and 23 C

Cefotaxime sodium RS 20 g RP 5 ga Physically compatible with little or no pH change for at least 24 hr at 4 C

807 C

HO 10 g AB 5 g Potency of both drugs by HPLC retained for 72 hr at 8 C 1547 C

HO 10 g AB 5 g

Visually compatible with 10% cefotaxime loss by HPLC in 19 hr at 28 C and 8% loss in 96 hr at 5 C. No metronidazole loss in 96 hr at 5 or 28 C

1754 C

Cefoxitin sodium FC 30 g RP 5 ga Physically compatible with little or no pH change for at least 24 hr at 4 C

807 C

FC 30 g RP 5 ga Physically compatible, but pH changed significantly in 6 to 12 hr at 23 C

807 ?

MSD 30 g SE 5 g 9% cefoxitin loss in 48 hr at 25 C and 3% in 12 days at 5 C. No metronidazole loss

993 C

Ceftazidime GLc 20 g 5 g No loss of either drug in 4 hr 1345 C

LIc 10 g AB 5 g Visually compatible with little or no loss of either drug by HPLC in 72 hr at 8 C

1849 C

Ceftizoxime sodium FUJ 10 g AB 5 g


1849 C

SKB 10 g AB 5 g

Visually compatible with 8 to 9% loss of both drugs by HPLC in 14 days at 4 C followed by 48 hr at 25 C. 3 to 4% loss of both drugs in 3 days and 10 to 13% in 5 days at 25 C

1879 C

Ceftriaxone sodium RC 10 g AB 5 g Visually compatible with little or no loss of either drug by HPLC in 72 hr at 8 C

1849 C

RC 10 g BA 5 g

Visually compatible with no metronidazole loss by HPLC and with 6% ceftriaxone loss in 3 days and 8% in 4 days at 25 C

2101 C

Cefuroxime sodium GL 7.5 g 5 g Physically compatible with no

loss of either drug in 1 hr 1036 C

GL 15 g 5 g No loss of either drug in 4 hr at 24 C 1376 C

GL 7.5 g 5 g

10% cefuroxime loss by HPLC in 16 days at 4 C and 35 hr at 25 C. No metronidazole loss by HPLC in 15 days at 4 and 25 C

1565 C

GL 7.5 and 15 g IVX 5 g

Physically compatible with no visible precipitation or increase in measured particulates. No loss of metronidazole and about 6% cefuroxime loss in 49 days at 5 C

2192 C

Chloramphenicol sodium succinate PD 10 g RP 5 ga

Physically compatible with little or no pH change for at least 72 hr at 23 C

807 C

Ciprofloxacin 2 g 5 g No loss of either drug in 4 hr at 24 C 1346 C

MI 1.6 g SE 4.2 g

Visually compatible and potency of both drugs by HPLC retained for 48 hr at 25 C under fluorescent light and 4 C in the dark

1541 C

1 g RPR 2.5 g

Less than 3% loss of metronidazole in 24 hr at 25 C under room light or protected from light. Ciprofloxacin not tested

2361 C

BAY 1 g SCS 2.5 g

Visually compatible with no loss of ciprofloxacin in 24 hr at 22 C under fluorescent light. Metronidazole not tested

2413 C

Clindamycin phosphate UP 10 g RP 5 ga

Physically compatible with little or no pH change for at least 24 hr at 23 C

807 C

Floxacillin sodium BE 10 g 5 g

Physically compatible for 48 hr. Potency of both drugs retained when assayed after 1 hr at room temperature

1036 C

Fluconazole PF 1 g AB 2.5 g

Visually compatible with no fluconazole loss by HPLC in 72 hr at 25 C under fluorescent light. Metronidazole not tested

1677 C

Gentamicin sulfate RS 800 mg RP 5 ga Physically compatible with little or no pH change for at least 72 hr at 23 C

807 C

EX 800 mgd 5 g Physically compatible with no loss of either drug in 1 hr 1036 C

SC800 mg and 1.2 g

SE 5 g

Physically compatible with no loss of either drug in 2 days at 18 C. At 4 C, no metronidazole loss but up to 10% gentamicin loss in 7 days

1242 C

800 mg RP 5 g

Visually compatible with no loss of metronidazole by HPLC in 15 days at 5 and 25 C. 10% gentamicin loss by immunoassay in 63 hr at 25 C and 10.6 days at 5 C

1931 C

Hydrocortisone sodium succinate UP 10 g RP 5 ga

Physically compatible for at least 72 hr at 23 C, but pH changed significantly

807 ?

ES 10 g SE 5 g No loss of either drug for 7 days at 25 C and 12 days at 5 C

993 C

Midazolam HCl RC 50, 250, 400 mg 5 g NS Visually compatible for 4 hr 355 C

Penicillin G potassium AY

12 million units

RP 5 ga Physically compatible for at least 72 hr at 23 C, but pH changed significantly

807 ?

PF200 million units

SE 5 g

5% penicillin loss in 22 hr and 8% in 72 hr at 25 C. 2% penicillin loss in 12 days at 5 C. No metronidazole loss

993 C

Tobramycin sulfate LI 800 mg RP 5 ga Physically compatible with little or no pH change for at least 72 hr at 23 C

807 C

LI 1 g RP 5 g

Visually compatible with no loss of metronidazole by HPLC in 15 days at 5 and 25 C. 10% tobramycin loss by immunoassay in 73 hr at 25 C and 12.1 days at 5 C

1931 C

aMinibags (100 mL) containing metronidazole 500 mg with disodium phosphate 150 mg, citric acid 44 mg, and sodium chloride 740 mg. This product differs from the SCS Pharmaceuticals product.


cSodium carbonate-containing formulation tested.

dTested in both dextrose 5% and sodium chloride 0.9%.


MetronidazoleDrug Mfr Conc Mfr Conc Remarks Ref C/I

Acyclovir sodium BW 5 mg/mLa SE 5 mg/mL


Allopurinol sodium BW 3 mg/mLb BA 5 mg/mL


1686 C

Amifostine USB 10 mg/mLa BA 5 mg/mL


1845 C


SEQ 0.83 mg/mLa AB 5

mg/mL Gross precipitate forms 2117 I

Anidulafungin VIC 0.5 mg/mLa BA 5 mg/mL


2617 C

Aztreonam SQ 40 mg/mLa BA 5 mg/mL

Color changes from colorless to orange in 4 hr 1758 I

Bivalirudin TMC 5 mg/mLa BA 5 mg/mL


2373 C

Cefepime HCl BMS 20 mg/mLa BA 5 mg/mL


1689 C

Cisatracurium besylate GW 0.1, 2, and 5 mg/mLa

AB 5 mg/mL

Physically compatible with no change in measured turbidity or increase in

2074 C

particle content in 4 hr at 23 C

Clarithromycin AB 4 mg/mLa PRK 5 mg/mL

Visually compatible for 72 hr at both 30 and 17 C 2174 C

Cyclophosphamide MJ 20 mg/mLa SE 5 mg/mL


Dexmedetomidine HCl AB 4 g/mLb BA 5 mg/mL


2383 C

Diltiazem HCl MMD 5 mg/mL SE 5 mg/mL Visually compatible 1807 C

Dimenhydrinate 10 mg/mL 5 mg/mL Clear solution 2569 C

Docetaxel RPR 0.9 mg/mLa BA 5 mg/mL


2224 C

Dopamine HCl AB 0.8 mg/mLa MG 5 mg/mL


2063 C

Doxapram HCl RB 2 mg/mLa AB 5 mg/mL


Doxorubicin HCl liposome injection SEQ 0.4 mg/mLa AB 5

mg/mL


2087 C


mg/mLb BA 5 mg/mLb Strands form within 4 hr 2615 I

Enalaprilat MSD 0.05 mg/mLb SE 5

mg/mL


1355 C

Esmolol HCl DCC 10 mg/mLa SE 5 mg/mL


Etoposide phosphate BR 5 mg/mLa AB 5 mg/mL


2218 C

Fenoldopam mesylate AB 80 g/mLb BA 5 Physically compatible with 2467 C

mg/mL

no increase in measured haze or particle content in 4 hr at 23 C under fluorescent light

Filgrastim AMG 30 g/mLa BA 5 mg/mL

Particles form immediately with filaments in 1 hr 1687 I

Fluconazole RR 2 mg/mL AB 5 mg/mL


Foscarnet sodium AST 24 mg/mL AB 5 mg/mL


1335 C

AST 24 mg/mL SE 5 mg/mL


1393 C

Gemcitabine HCl LI 10 mg/mLb AB 5 mg/mL


2226 C

Granisetron HCl SKB 0.05 mg/mLa BA 5

mg/mL


2000 C

Heparin sodium TR 50 units/mL MG 5



AB 6% AB 5 mg/mL


2339 C

Hydromorphone HCl WY 0.2 mg/mLa SE 5 mg/mL


987 C

Labetalol HCl SC 1 mg/mLa SE 5 mg/mL


Linezolid PHU 2 mg/mL BA 5 mg/mL


2264 C

Lorazepam WY 0.33 mg/mLb BRN 5


Magnesium sulfate IX 16.7, 33.3, SE 5 Physically compatible for at 813 C

66.7, 100 mg/mLa mg/mL least 4 hr at 32 C

Melphalan HCl BW 0.1 mg/mLb AB 5 mg/mL


1557 C

Meperidine HCl WY 10 mg/mLa SE 5 mg/mL


987 C

Methylprednisolone sodium succinate UP 5 mg/mLa MG 5

mg/mL


2063 C

Midazolam HCl RC 1 mg/mLa BA 5 mg/mL


RC 5 mg/mL BRN 5 mg/mL


Milrinone lactate SS 0.2 mg/mLa AB 5 mg/mL


Morphine sulfate WI 1 mg/mLa SE 5 mg/mL


987 C

Nicardipine HCl DCC 0.1 mg/mLa SE 5 mg/mL


Pantoprazole sodium 4 mg/mL 5 mg/mL Precipitates within 15 min 2574 I

Pemetrexed disodium LI 20 mg/mLb BA 5 mg/mL

Color darkening and brownish discoloration occur immediately

2564 I

Piperacillin sodium-tazobactam sodium LE 40 + 5

mg/mLa BA 5 mg/mL


1688 C


AB 5 mg/mL


2075 C

Sargramostim IMM 10 g/mLb MG 5 mg/mL


Tacrolimus FUJ 1 mg/mLb AB 5 mg/mL


Teniposide BR 0.1 mg/mLa BA 5 mg/mL


1725 C

Theophylline TR 4 mg/mL MG 5 mg/mL


Thiotepa IMMc 1 mg/mLa BA 5 mg/mL


1861 C

TNA #218 to #226d AB 5 mg/mL


2215 C

TPN #189d DB 5 mg/mL


TPN #203 and TPN #204d AB 5


TPN #212 to #215d SCS 5 mg/mL


2109 C

Vasopressin APP 0.2 unit/mLb AB 5

mg/mLVisually and microscopically compatible 2641 C

Vinorelbine tartrate BW 1 mg/mLb BA 5 mg/mL


1558 C



cLyophilized formulation tested.

dRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3-in-1 admixture, and TPN indicates a 2-in-1 admixture.

eSodium carbonate-containing formulation tested.


Other Drugs It is recommended that no other drug be added to infusions of metronidazole ready-to-use. Furthermore, if administration of metronidazole is to be made through the tubing of an ongoing primary infusion, the primary infusion should be stopped, if possible, during metronidazole administration. (1-4/06) (4)

Aluminum The discoloration interaction that occurs between reconstituted metronidazole hydrochloride and aluminum in needle hubs does not occur as readily with the ready-to-use metronidazole solution. Discoloration is not apparent when administration is completed within one hour. However, the solution may discolor and a precipitate may form after contact with aluminum for six or more hours. (4) (707) (1116) (1117) Also see Metronidazole Hydrochloride monograph.

References








ISBN: o ISBN-13: 978-1-58528-213-5




Title:


o Handbook on Injectable Drugs - 15th Ed. (2009) Date Posted:

o 11/4/2009 4:31:06 PM CDT (UTC -05:00) Electronic Address:

o http://online.statref.com/document.aspx?fxid=141&docid=232 Date Accessed:

o 8/21/2010 3:39:38 AM CDT (UTC -05:00) Location In Title:

o HANDBOOK ON INJECTABLE DRUGS - 15th Ed. (2009) "M" Monographs Metronidazole - AHFS 8:30.04


Morphine Sulfate - AHFS 28:08.08

Products Morphine sulfate is available in a variety of concentrations and sizes ranging from 0.5 to 50 mg/mL. The Astramorph PF and Duramorph 0.5- and 1-mg/mL concentrations and the Infumorph 200- (10 mg/mL) and Infumorph 500- (25 mg/mL) formulations are preservative free. Morphine hydrochloride and morphine tartrate injections are also available in some countries. Other morphine products may contain various preservatives, antioxidants, and buffers, including chlorobutanol, phenol, sodium bisulfite, sodium phosphates, and sodium formaldehyde sulfoxylate. (4) (29) (38)

pH From 2.5 to 6.5 for most products. Duramorph has a pH of 3.5 to 7, and Infumorph has a pH of about 4.5. (4) (17) Morphine sulfate (David Bull) 7.5 mg/mL in sodium chloride 0.9% had a pH of 3.5. (2161)

Morphine hydrochloride solutions diluted in sodium chloride 0.9% are reported to be near pH 4 to 5. (1312)

/w EPDw ULLTE4N

Osmolality The osmolality of morphine (as the hydrochloride) 10 mg/mL was determined to be 54 mOsm/kg. (1233) Morphine sulfate (David Bull) 7.5 mg/mL in sodium chloride 0.9% had an osmolality of 236 mOsm/kg. (2161)

Trade Name(s) Astramorph PF, Duramorph, Infumorph

Administration Morphine sulfate is usually administered subcutaneously but may be administered by intramuscular or slow intravenous injection and by slow continuous subcutaneous or intravenous infusion. For continuous intravenous infusion, a concentration of 0.1 to 1 mg/mL in dextrose 5% may be infused using an infusion control device, although more concentrated solutions also have been used. Duramorph, Infumorph, and Astramorph PF contain no preservatives and may be administered intrathecally or epidurally. (1-11/6) (1-12/04) (4)

High-concentration morphine sulfate is not recommended for subcutaneous, intramuscular, or intravenous injection of individual doses or for intrathecal or epidural administration. The products are intended for continuous intravenous infusion using a suitable microinfusion control device. (4)

Stability Morphine sulfate injections are clear, colorless solutions. Intact containers should be stored at controlled room temperature and protected from freezing and light. Morphine sulfate darkens upon prolonged exposure to light. (4)

Undiluted morphine sulfate (Allen Hanburys) 10 mg/mL, stored in 100-mL glass vials and PVC bags, exhibited no loss in 30 days at 23 C. (1394)

Morphine sulfate (Wyeth) 1 mg/mL in bacteriostatic sodium chloride 0.9% containing benzyl alcohol 0.9%, when stored in glass vials with protection from light, exhibited no loss by HPLC at 4 C and a 4% loss at 22 C after 91 days. (1583)

Duafala et al. studied the stability of morphine sulfate 15 and 2 mg/mL diluted with sterile water for injection at 4 and 24 C in 200-mL PVC bags (Baxter). Both concentrations were stable at both temperatures with little or no loss in 15 days. (1504)

Morphine hydrochloride physical and chemical stability were evaluated at concentrations ranging from 10 to 50 mg/mL in water, dextrose 5%, and sodium chloride 0.9% for use in subcutaneous infusion. The solutions were stored in glass containers, polypropylene syringes, and PVC containers at 4, 22, and 40 C for up to three months in the absence of light. At concentrations above 20 mg/mL, refrigerated storage resulted in the formation of visually apparent precipitation that was difficult to redissolve. Precipitation also occurred at concentrations above 30 mg/mL using sodium chloride 0.9% as the diluent. The solution color increased progressively from colorless to pale yellow initially to darker yellow and to brown in the 40 C samples. HPLC analysis of morphine sulfate 30-mg/mL aqueous solutions found no substantial decomposition of morphine sulfate within three months at 22 C, but the authors recommended that refrigerated storage be avoided because of the potential for precipitation. In addition, the solutions in PVC containers exhibited a gradual increase in drug concentration and osmolality possibly indicating a loss of water through the PVC. The morphine concentration increased to over 105% after storage of one month and one week at 22 and 40 C, respectively. In

addition, a white precipitate formed, possibly because of water evaporation. Storage in PVC containers for longer time periods was not recommended. (2162)

Morphine sulfate under simulated summer conditions in paramedic vehicles was exposed to temperatures ranging from 26 to 38 C over four weeks. Analysis found no loss of the drug under these conditions. (2562)

Morphine sulfate 1 mg/mL compounded in sodium chloride 0.9% was packaged in 100-mL polypropylene infusion bags and was autoclaved at 121 C for 20 minutes for sterilization. No visible precipitation appeared and microparticulate levels remained acceptable in all samples when stored at 25 C for three years and at 30 and 40 C for six months. No evidence of evaporation was found in the samples, and no loss of morphine sulfate by stability-indicating HPLC analysis occurred in any of the solutions throughout the study. While PVC bags cannot be autoclaved and exhibit excessive loss of water through evaporation upon storage, polypropylene bags can be successfully used for compounding bags of morphine sulfate solutions with long-term (three-year) stability for use in patient-controlled analgesia. (2665)

pH Effects Morphine sulfate is relatively stable at acidic pH, especially below pH 4, but degradation increases greatly at neutral or basic pH. Degradation is often accompanied by a yellow to brown discoloration in the normally colorless solution. (1072) (2170)

Freezing Solutions Morphine sulfate (Lilly) 1 and 2 mg/mL in dextrose 5% and sodium chloride 0.9% in PVC bags exhibited no loss during 14 weeks of frozen storage at -20 C. (1286)

Syringes Prefilled into plastic syringes with syringe caps (Braun), morphine sulfate is stated to remain within acceptable limits of degradation for at least 69 days at room temperature. (982)

In another study, less than a 3% loss of morphine sulfate occurred in 12 weeks when stored in plastic syringes at 22 C and exposed to light. A smaller loss occurred when the morphine sulfate was stored at 3 C with light protection. (1287)

Duafala et al. studied the stability of morphine sulfate 15 and 2 mg/mL diluted with sterile water for injection at 4 and 24 C in 3-mL disposable glass syringes (Hypod). Both concentrations were stable at both temperatures with little or no loss in 12 days. (1504)

Morphine sulfate (Lilly) 1 and 5 mg/mL in dextrose 5% and sodium chloride 0.9% was packaged in 30-mL Plastipak (Becton-Dickinson) syringes capped with Monoject (Sherwood) tip caps. Syringes were stored at 23 C exposed to light and protected from light, 4 C protected from light, and frozen at -20 C protected from light for 12 weeks. HPLC analysis found that both concentrations at all three temperatures were stable for at least six weeks when protected from light. However, the samples at 23 C exposed to light were stable for a week, but some developed unacceptable losses after that. (1894)

Grassby and Hutchings reported the stability of morphine sulfate 2 mg/mL in sodium chloride 0.9% packaged in 50-mL (Becton-Dickinson) and 30-mL (Becton-Dickinson and Sherwood) polypropylene syringes for use in patient-controlled analgesia and in stoppered glass vials. The morphine sulfate solution packaged in the syringes and glass vials was stored at room temperature in the dark for six weeks. Using HPLC analysis, the authors found little or no loss of

morphine sulfate content in the 50-mL syringes and the glass vials in six weeks. About 5% loss occurred when packaged in both brands of 30-mL syringes. Addition of sodium metabisulfite 0.1% as an antioxidant substantially increased the rate of drug loss; up to 10% loss occurred in two weeks. (2040)

The stability of morphine hydrochloride 1, 5, and 10 mg/mL in dextrose 5% and 0.9% sodium chloride packaged in 50-mL polypropylene syringes (B. Braun and Becton-Dickinson) was evaluated. HPLC analysis found little or no loss, with degradation products being less than 2% of the concentration when stored at 37 C for two days. (2169)

Morphine tartrate (David Bull) 80 mg/mL (undiluted) and 4 mg/mL diluted in sodium chloride 0.9% was packaged as 10 mL of solution in polypropylene syringes (Terumo) sealed with tip caps (Terumo). Samples were stored in the dark at 4 and 22 C for 21 days. The refrigerated samples at both concentrations and the 4-mg/mL concentration at 22 C underwent no visible changes and HPLC analysis found little or no loss. The 80-mg/mL samples stored at 22 C developed a slight yellow discoloration within 21 days that was considered to be within the normal color range for this product. HPLC analysis found about 7% loss after 21 days. (1461)

Preservative-free morphine (salt form unspecified) 0.1 to 1 mg/mL in sodium chloride 0.9% was packaged in 60-mL polypropylene syringes (Monoject) and stored at room temperature. HPLC analysis found no loss of morphine after 36 hours. (631)

Morphine sulfate 5 mg/mL in sodium chloride 0.9% and 50 mg/mL in sterile water for injection and also in sodium chloride 0.9% packaged as 20 mL in 30-mL polypropylene syringes was evaluated for physical and chemical stability. Sample solutions were stored for 60 days at 4 C protected from light and 23 C exposed to normal fluorescent light. Other sample solutions were stored frozen at -20 C and at elevated temperature of 37 C for two days to simulate more extreme conditions during express shipping. HPLC analysis found little or no morphine sulfate loss in the 50-mg/mL samples stored for 60 days at 4 and 23 C even though slight yellow discoloration appeared after 30 days. The 5-mg/mL samples stored at 4 and 23 C exhibited about 4 to 5% loss in 60 days. The frozen and 37 C samples exhibited little or no change in morphine sulfate concentration in two days. However, samples of the 50-mg/mL concentration stored at -20 and 4 C and samples of the 5-mg/mL concentration stored frozen at -20 C precipitated upon low temperature storage. Although the precipitate redissolved upon warming at 37 C for several hours, large amounts of microparticulates in the tens of thousands per milliliter remained, possibly shed by the syringe components. (2376)

Ambulatory Pumps Walker et al. reported the stability of morphine sulfate (Sabex) 50 and 25 mg/mL and 10 mg/mL diluted in dextrose 5% and sodium chloride 0.9%, with and without sodium metabisulfite preservative, in portable infusion pump cassettes (Pharmacia) stored at 4 and 23 C. At all concentrations with or without preservatives at both temperatures, samples remained clear and colorless. Morphine sulfate losses of approximately 5 to 8% were found during 31 days of storage. (1505)

Altman et al. evaluated the stability of morphine sulfate 0.5, 15, 30, and 60 mg/mL in sodium chloride 0.9% stored in Kalex (Cormed III) bags at 5 and 37 C. The 60-mg/mL concentration exhibited precipitation in four to eight days when refrigerated. The maximum solubility of

morphine sulfate at room temperature is 62.5 mg/mL; refrigeration reduced the solubility, causing precipitation. All other solutions were clear, with no evidence of precipitation. HPLC analysis showed no loss during 14 days of storage at either temperature. A small concentration increase in samples stored at 37 C was attributed to water evaporation. (1506)

Stiles et al. studied the stability of morphine sulfate 25, 15, 5 and 1 mg/mL (with the latter two concentrations prepared in sodium chloride 0.9%) in pump reservoirs (Pharmacia Deltec) stored at 5 and 25 C for 30 days. After the initial storage period, the solutions were subsequently stored at 37 C and pumped at a flow rate of 0.4 mL/hr to simulate patient use. No color change or precipitation occurred in any sample. No losses were detected by HPLC; in fact, increased concentrations were observed, especially at room temperature. The concentration increases were attributed to water evaporation during storage. The authors recommended a maximum storage of 30 days under refrigeration and 14 days at room temperature because of the evaporation. (1507)

Morphine hydrochloride (Merck) 20 mg/mL was filled into 50-mL ambulatory infusion pump cassette reservoirs (Pharmacia Deltec) and stored at room temperature and protected from light for 90 days. HPLC analysis found no loss of the drug. Instead, the drug concentration increased 13% during the observation period, possibly due to loss of water from the solutions. (1850)

The stability of morphine hydrochloride 20 mg/mL (undiluted) and 1 mg/mL diluted with dextrose 5% or sodium chloride 0.9% packaged in ambulatory infusion pump cassettes (B. Braun and Deltec) was evaluated. HPLC analysis found no evidence of drug loss, with degradation products being less than 2% of the concentration when stored at 37 C for 14 days. However, morphine concentration increases of up to 12% over the study period were observed in some samples presumably because of loss of water. (2169)

Hor et al. reported the stability of morphine sulfate 1 and 10 mg/mL in sodium chloride 0.9% filled in 100-mL Deltec medication cassette reservoirs. The reservoirs were stored at 32 C at 37% relative humidity and protected from light for 16 days to simulate use conditions. HPLC analysis found no morphine loss and no formation of decomposition products. However, a 4% increase in morphine sulfate concentration occurred during the study period that is consistent with a small amount of evaporation occurring. (2254)

Morphine hydrochloride (Centrafarm) 0.5, 1.5, and 2.5 mg/mL in sodium chloride 0.9% was packaged in PVC/Kalex phthalate ester medication cassette reservoirs (Pharmacia Deltec) and stored at 32 C to simulate in use conditions close to the body. No visually apparent change occurred, and HPLC analysis found no morphine decomposition after 60 days of storage. However, evaporation of about 0.8 mL/week was found, resulting in a concentration effect on the morphine hydrochloride of about 1% per week. After 60 days, morphine hydrochloride concentrations were generally near 107 to 109% of the initial concentration. (1312)

Elastomeric Reservoir Pumps Duafala et al. studied the stability of morphine sulfate 15 and 2 mg/mL diluted with sterile water for injection at 4 and 24 C in Intermate 200 (Infusion Systems) and Infusor (Baxter) disposable elastomeric infusion devices. In the Intermate 200 with 100 mL of morphine sulfate solution, little or no loss occurred in 15 days at either 4 or 24 C and even at 31 C (simulating use next to a patient's skin or clothing). In the Infusor, with 50 mL, losses of 5% or more were observed in 12 days in some containers. (1504)

Morphine sulfate 0.5 mg/mL in both dextrose 5% and sodium chloride 0.9% was evaluated for binding potential to natural rubber elastomeric reservoirs (Baxter). No binding was found after storage for two weeks at 35 C with gentle agitation. (2014)

Morphine hydrochloride 2.5 and 5 mg/mL in 0.9% sodium chloride with and without the antioxidant sodium metabisulfite was filled into 60-mL Infusors (Baxter) and stored at room temperature exposed to or protected from light. HPLC analysis found 6% or less variation in the morphine concentration over a month. The formation of the decomposition product pseudomorphine was greatest without the metabisulfite in the samples exposed to light. Up to 1.5% formed in 30 days. No decomposition products formed if the metabisulfite was present. (2176)

Morphine sulfate 2 and 10 mg/mL is reported to be physically and chemically stable in Accufuser Plus silicone balloon infusers when stored at room temperature and refrigerated. HPLC analysis found little or no loss of morphine sulfate in 40 days. (2678)

Morphine sulfate solutions in elastomeric reservoir pumps have been stated by the pump manufacturers to be stable for the following time periods frozen, refrigerated (REF), or at room temperature (RT) (31) :

Pump Reservoir(s) Conc. Frozen REF RTHomepump; Homepump Eclipse 20 mg/mLb 7 daysInfusor 1 to 20 mg/mLa 57 daysc 7 days 1 to 20 mg/mLb 87 daysc 7 days 5 to 20 mg/mLb 177 daysc 7 daysaIn dextrose 5%.bIn sodium chloride 0.9%.cStable for an additional three days at room temperature after low temperature storage.

Implantable Pumps Morphine sulfate 10 mg/mL was filled into a VIP 30 implantable infusion pump (Fresenius) and associated capillary tubing and stored at 37 C. Samples were analyzed using an HPLC assay. No morphine loss and no contamination from components of pump materials occurred during eight weeks of storage. (1903)

Undiluted morphine sulfate (unspecified concentration) was stated to be stable for 90 days at room temperature or at body temperature in the Synchromed pump (Medtronic). (31)

Baclofen (Ciba) 0.2 mg/mL with morphine sulfate (David Bull) 1 mg/mL in an implantable pump (Infusaid) was physically compatible and exhibited little or no loss of either drug within 30 days at 37 C. (1911)

In a follow-up study at higher concentrations, baclofen (Ciba) 1 mg/mL with morphine sulfate (David Bull) 15 mg/mL in an implantable pump (Infusaid) was physically compatible, with only a slight yellowing of the solution observed. HPLC analysis found no change in the baclofen concentration and 5% or less morphine loss after 30 days at 37 C. (2170)

Morphine sulfate (Infumorph) 20 mg/mL with clonidine hydrochloride (Boehringer Ingelheim) 50 g/mL and morphine sulfate 2 mg/mL with clonidine hydrochloride 1.84 mg/mL were evaluated in SynchroMed EL (Medtronic) implantable pumps with silicone elastomer intrathecal catheters at 37 C for three months. No visible incompatibilities were observed; stability-indicating HPLC analysis found that delivered concentrations of both drugs were in the range of 94.0 to 99.6% of the theoretical concentrations throughout the study. Furthermore, no impairment of mechanical performance of the pump or any of its components was found. (2477)

An admixture of bupivacaine hydrochloride 25 mg/mL, clonidine hydrochloride 2 mg/mL, and morphine sulfate 50 mg/mL in sterile water for injection was reported to be physically and chemically stable for 90 days at 37 C in SynchroMed implantable pumps. HPLC analysis found little or no loss of any of the drugs. (2585)

Other Devices Caute et al. evaluated the stability of two intrathecal solutions of morphine sulfate 10 mg/mL in sodium chloride 0.9% (isobaric) and 5 mg/mL in dextrose 7% in water (hyperbaric). The solutions were stored at 4 and 37 C in glass ampuls and pump reservoirs composed of silicone rubber reinforced with polyester (Cordis Europa). No precipitation or discoloration and no loss of morphine sulfate or increase in degradation products occurred in the solutions in glass ampuls after two months at either temperature. However, in the pump reservoirs, the isobaric solution in sodium chloride 0.9% developed a yellow color. Furthermore, a decomposition product, pseudomorphine, was detectable in three days and increased to 1% in one month at 37 C. This level was 20 times that of the pseudomorphine found in the hyperbaric dextrose 7% in water solution under the same conditions. The decomposition was attributed to dissolved oxygen, ethylene oxide sterilant, and silicone rubber. (1508)

Sorption Morphine hydrochloride (British Drug Houses) 75 mg/L in sodium chloride 0.9% (Travenol) in PVC bags did not exhibit significant sorption to the plastic during one week of storage at room temperature (15 to 20 C). (536)

In another study, morphine hydrochloride (British Drug Houses) 75 mg/L in sodium chloride 0.9% did not exhibit any loss due to sorption during a seven-hour simulated infusion through an infusion set (Travenol) consisting of a cellulose propionate burette chamber and 170 cm of PVC tubing. (606)

The drug was also tested as a simulated infusion over at least one hour by a syringe pump system. A glass syringe on a syringe pump was fitted with 20 cm of polyethylene tubing or 50 cm of Silastic tubing. No loss of drug due to sorption was observed with either tubing. (606)

A 25-mL aliquot of morphine hydrochloride (British Drug Houses) 75 mg/L in sodium chloride 0.9% was stored in all-plastic syringes composed of polypropylene barrels and polyethylene plungers for 24 hours at room temperature in the dark. No loss due to sorption occurred. (606)

Filtration Adsorption to cellulose acetate membrane filters was less than 3% for morphine hydrochloride 10 to 50 mg/mL in water, dextrose 5%, and sodium chloride 0.9%. (2162)

Central Venous Catheter Morphine sulfate (Astra) 1 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. HPLC analysis was used to evaluate completeness of drug delivery

through the catheter and the amount of chlorhexidine removed from the internal lumens. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter. (2335)



Morphine sulfateSolution Mfr Mfr Conc/L Remarks Ref C/IDextran 6% in dextrose 5% AB 16.2 mg Physically compatible 3 C

Dextran 6% in sodium chloride 0.9%

AB 16.2 mg Physically compatible 3 C

Dextrose-Ringer's injection combinations


Dextrose-Ringer's injection, lactated, combinations


Dextrose-saline combinations AB 16.2 mg Physically compatible 3 C

Dextrose 2.5% AB 16.2 mg Physically compatible 3 CDextrose 5% AB 16.2 mg Physically compatible 3 C

Dextrose 5% TRa LI 1.2 g Physically compatible and no morphine loss in 36 hr at 22 C 1000 C

Dextrose 5% TRb AB, AH

40 and 400 mg

Physically compatible with little or no loss in 7 days at 23 and 4 C 1349 C

Dextrose 5% a AH 5 g No morphine loss in 30 days at 23 C 1394 C

Dextrose 5% g SX 10 gVisually compatible with morphine losses of 5 to 8% by HPLC in 31 days at 4 and 23 C

1505 C

Dextrose 5% ej c 1 gLittle or no decomposition by HPLC in 14 days at 37 C, but concentration increased by up to 12% due to evaporation

2169 C

Dextrose 10% AB 16.2 mg Physically compatible 3 CFructose 10% in sodium chloride 0.9%


Fructose 10% AB 16.2 mg Physically compatible 3 CInvert sugar 5 and 10% in sodium chloride 0.9%


Invert sugar 5 and 10% AB 16.2 mg Physically compatible 3 C

Ionosol products (unless otherwise noted)


Ringer's injection AB 16.2 mg Physically compatible 3 CRinger's injection, lactated AB 16.2 mg Physically compatible 3 C

Sodium chloride 0.45% AB 16.2 mg Physically compatible 3 C

Sodium chloride 0.9% AB 16.2 mg Physically compatible 3 C

Sodium chloride 0.9% TRb AB,

AH40 and 400 mg

Physically compatible with little or no loss in 7 days at 23 and 4 C 1349 C


a AH 5 g No morphine loss in 30 days at 23 C 1394 C

Sodium chloride 0.9% GRIa 140 and

190 mgcNo change in concentration by UV in 28 days at 4 C and room temperature 1910 C

Sodium chloride 0.9% ABa SCN 100 and

500 mg

Visually compatible with no loss by HPLC in 72 hr at 24 C under fluorescent light

2058 C


e PHS 1 and 10 g

Visually compatible with no loss by HPLC within 16 days at 32 C protected from light. A 4% increase in concentration was consistent with a small amount of evaporation

2254 C


f CNF 0.5, 1.5, 2.5 g

Visually compatible with no loss by HPLC within 60 days at 32 C. About 8% increase in concentration was found due to evaporation

1312 C


g SX 10 g Visually compatible with morphine losses of 5 to 8% by HPLC at 4 and 23 C 1505 C


h 0.5, 15, 30 gi

No morphine loss by HPLC in 14 days at 5 C and a small increase in concentration at 37 C due to evaporation. Light brown discoloration observed after 5 days at 37 C

1506 C


h 60 gi

At 37 C, a small increase in morphine concentration in 14 days due to evaporation. Light brown discoloration observed after 5 days

1506 C


h 60 giAt 5 C, morphine precipitates in as little as 4 days with morphine losses by HPLC of over 40%

1506 I

Sodium chloride e ES 1 and 5 g Visually compatible for 30 days at 5 and 1507 C

0.9%

25 C. HPLC found increased morphine concentration due to evaporation. Maximum storage of 30 days at 5 C and 14 days at 25 C


ej c 1 gLittle or no decomposition by HPLC in 14 days at 37 C, but concentration increased by up to 12% due to evaporation

2169 C

Sodium chloride 0.9% BAk i 5 g

Physically compatible with about 4 to 5% morphine loss by HPLC in 60 days at 23 C under fluorescent light and at 4 C protected from light

2376 C


Physically compatible with little or no morphine loss by HPLC in 60 days at 23 C under fluorescent light. Slight yellow discoloration not indicative of decomposition

2376 C


At 4 C, morphine sulfate precipitates. Warming redissolves the precipitate, but leaves tens of thousands of microparticulates. Little or no morphine loss by HPLC in 60 days at 4 C protected from light

2376 ?

Sodium chloride 0.9% MACe AGT 1 and 40

g

Physically compatible with no loss in 30 days at room temperature protected from light. Concentration increase due to water loss

2633 C

Sodium chloride 0.9% BAm ANT 2 and 3 g

Physically compatible with little or no drug loss in 60 days at 4 and 25 C. Less than 2.5% loss of moisture during storage

2628 C

Sodium lactate (1/6) M AB 16.2 mg Physically compatible 3 C

Sterile water for injection (Note: Not suitable for large-volume infusion.)

BAk i 50 g

Physically compatible with little or no morphine loss by HPLC in 60 days at 23 C under fluorescent light. Slight yellow discoloration not indicative of decomposition

2376 C

Sterile water for injection BAk i 50 g

At 4 C, morphine sulfate precipitates. Warming redissolves the precipitate, but leaves tens of thousands of microparticulates. Little or no morphine loss by HPLC in 60 days at 4 C under fluorescent light

2376 ?

TPN #71d a LI 100 mg Physically compatible and no morphine loss in 36 hr at 22 C 1000 C

TPN #248d c l 3, 36, 74 Little or no morphine loss in 28 days at 4 2454 C

mg and 20 C exposed to light

TPN #249d c l 3, 47, 94 mg

Little or no morphine loss in 28 days at 4 and 20 C exposed to light 2454 C


bTested in both glass and PVC containers.

cTested as the hydrochloride salt.

dRefer to Appendix I for the composition of parenteral nutrition solutions. TPN indicates a 2-in-1 admixture.

eTested in Pharmacia or SIMS Deltec medication cassette reservoirs.

fTested in Pharmacia Deltec PVC/Kalex phthalate ester medication cassette reservoirs.

gTested in Pharmacia cassette reservoirs.

hTested in Cormed III Kalex reservoirs.

iPrepared from morphine sulfate powder.

jTested in B. Braun pump cassettes.

kTested in polypropylene syringes.

lTested in polyethylene chloride bags.

mTested in ANAPA Plus (E-WHA International) ambulatory infusion device and PEGA (Pegasus) sets.


Morphine sulfate


Alteplase GEN 0.5 g WY 1 g NSVisually compatible with 5 to 8% alteplase clot-lysis activity loss in 24 hr at 25 C

1856 C

Aminophylline Physically incompatible 9 IAmobarbital sodium Physically incompatible 9 I

Atracurium besylate

BW 500 mg 1 g D5W Physically compatible and atracurium chemically stable

1694 C

for 24 hr at 5 and 30 C

Baclofen CI 200 mg DB 1 and 1.5 g NSd

Physically compatible with little or no loss of either drug by HPLC in 30 days at 37 C

1911 C

CI 800 mg DB 1 g NSd

Physically compatible with little or no baclofen loss and less than 7% morphine loss by HPLC in 29 days at 37 C

1911 C

CI 800 mg DB 1.5 g NSdPhysically compatible with little or no loss of either drug by HPLC in 30 days at 37 C

1911 C

CI 1.5 g DB 7.5 g NSdPhysically compatible with little or no loss of either drug by HPLC in 30 days at 37 C

2170 C

CI 1 g DB 15 g NSdPhysically compatible with little or no loss of either drug by HPLC in 30 days at 37 C

2170 C

CI 200 mg DB 21 g NSd

Physically compatible with about 7% baclofen loss and little or no morphine loss by HPLC in 30 days at 37 C

2170 C

Bupivacaine HCl 850 mg 140 and 190 mga NSb

No change in concentration by UV in 28 days at 4 C and room temperature

1910 C

AST 3 g 1 g aLittle or no loss of either drug by HPLC in 30 days at 18 C

1932 C

AB625 mg and 1.25 g

SCN 100 mg NSb

Visually compatible with no loss of either drug by HPLC in 72 hr at 24 C under fluorescent light

2058 C

AB625 mg and 1.25 g

SCN 500 mg NSb


2058 C


25 g 2 g 50 g WiVisually compatible with little or no loss of any drug by HPLC in 90 days at 37 C

2585 C

Bupivacaine HCl with midazolam HCl

ICN RC

40 g 0.5 g DBLh 1 g NSg

Visually compatible. No loss of bupivacaine or morphine by HPLC in 42 days at 22 C in the dark. Midazolam loss of 10% in 28 days

2537 C

Chlorothiazide sodium MSD Physically incompatible 9 I

Dexamethasone sodium phosphate ME 440 mg GRUa 1.68 g NSk

Visually compatible for 7 days at 25 C protected from light

2701 C

ME 1.33 g GRUa 5 g NSkVisually compatible for 7 days at 25 C protected from light

2701 C

Dobutamine HCl LI 1 g ES 5 g D5W, NS


Floxacillin sodium BE 20 g EV 1 g WHaze forms in 24 hr and precipitate forms in 48 hr at 30 C. No change at 15 C

1479 I

Fluconazole PF 1 g ES 0.25 g D5Wb

Fluconazole chemically stable by gas chromatography for at least 24 hr at 25 C under fluorescent light. Morphine not tested

1676 C

Fluorouracil AB 1 and 16 g AST 1 g D5W,

NSb

Subvisual morphine precipitate forms immediately, becoming grossly visible within 24 hr. Morphine losses by HPLC of 60 to 80% occur within 1 day

1977 I

Furosemide HO 1 g EV 1 g W Physically compatible for 72 hr at 15 and 30 C 1479 C

Haloperidol lactate EST 210 mg GRUa 1.68 g NSk


2701 C

EST 620 mg GRUa 5 g NSkVisually compatible for 7 days at 25 C protected from light

2701 C

Heparin sodium Physically incompatible 9 I

Ketamine HCl PD 1 g SX 1 g NSb

Variable HPLC assays, but at least 90% of both drugs retained for 6 days at room temperature

2260 C

PD 25 g SX 25 g NSb


2260 C

PD 25 g SX 25 g NSe


2260 C

Ketoprofen lysine 2.7 g a 167 mg NSk Visually compatible with no 2691 C

loss of either drug by HPLC in 7 days at room temperature in the dark

5.3 g a 333 mg NSk

Visually compatible with no loss of either drug by HPLC in 7 days at room temperature in the dark

2691 C

Meperidine HCl WI Physically incompatible 9 I

Meropenem ZEN 1 and 20 g ES 1 g NS Visually compatible for 4 hr

at room temperature 1994 C

Metoclopramide HCl SKB 500 mg EV 1 g NSb

Visually compatible with little or no loss of either drug by HPLC in 35 days at 22 C and 182 days at 4 C followed by 7 days at 32 C

1939 C

SKB 500 mg EV 1 g D5Wc

Visually compatible with 8% metoclopramide loss by HPLC in 14 days at 22 C and 98 days at 4 C. No morphine loss occurs

1939 C

SYO 1.11 g GRUa 1.68 g NSkVisually compatible for 7 days at 25 C protected from light

2701 C

SYO 3.33 g GRUa 5 g NSkVisually compatible for 7 days at 25 C protected from light

2701 C

Midazolam HCl RC 400 mg 1 ga D5Wb14% morphine loss and 13% midazolam loss in 2 days by HPLC

192 ?

RC 400 mg 1 ga NSb13% morphine loss in 2 days and 10% midazolam loss in 5 days by HPLC

192 ?

RC 1 g 2 ga D5Wb

11% morphine loss in 2 days, but not more than 9% midazolam loss in 12 days by HPLC

192 ?

RC 1 g 2 ga NSb13% morphine loss in 2 days and 11% midazolam loss in 12 days by HPLC

192 ?

RC 0.5 g DBLh 1 g NSb

Visually compatible. No loss of morphine by HPLC in 42 days at 22 C in the dark. Midazolam loss of 10% in 28 days

2537 C

RC 500 mg GRUa 1.68 g NSk Visually compatible for 7 2701 C

days at 25 C protected from light

RC 1.5 g GRUa 5 g NSkVisually compatible for 7 days at 25 C protected from light

2701 C

Ondansetron HCl GL 100 mg and 1 g AST 1 g NSb

Physically compatible with no ondansetron loss and 5% or less morphine loss by HPLC in 7 days at 32 C or 31 days at 4 and 22 C protected from light

1690 C

Phenobarbital sodium WI Physically incompatible 9 I

Phenytoin sodium PD Physically incompatible 9 I

Ropivacaine HCl AZ 1 g AST 20 mga NSf

Visually and microscopically compatible with little or no loss of either drug in 30 days at 30 C in the dark

2433 C

AZ 2 g AST 20 and 100 mga

f


2433 C

Scopolamine butylbromide BI 1.68 g GRU 1.68 g NSk


2701 C

BI 5 g GRU 5 g NSkVisually compatible for 7 days at 25 C protected from light

2701 C

Sodium bicarbonate Physically incompatible 9 I

Succinylcholine chloride AB 2 g 16.2 mg Physically compatible 3 C

Thiopental sodium AB Physically incompatible 9 I

Verapamil HCl KN 80 mg KN 30 mg D5W, NS


Ziconotide acetate ELN 25 mg BB 35 g j

Morphine sulfate powder dissolved in ziconotide acetate injection. 90% ziconotide acetate retained for 8 days at 37 C. No morphine sulfate loss by HPLC in 28 days

2702 C

ELN 25 mg BB 20 g j Morphine sulfate powder dissolved in ziconotide acetate injection. 90%

2713 C

ziconotide acetate retained for 19 days at 37 C. No morphine sulfate loss by HPLC in 28 days

aTested as morphine hydrochloride.


cTested in PCA Infusors (Baxter).

dTested in glass containers.

eTested in Deltec plastic medication cassette reservoirs.

fTested in polypropylene bags (Mark II Polybags).

gTested in WalkMed PVC pump reservoirs.

hTested as the tartrate salt.

iTested in SynchroMed implantable pumps.

jTested in SynchroMed II implantable pumps.

kTested in elastomeric pump reservoirs (Baxter).


Morphine sulfateDrug (in syringe) Mfr Amt Mfr Amt Remarks Ref C/I

Alfentanil HCl AZ 55 mcg/mLe DB 0.8

mg/mLe

No loss of either drug in 182 days at room temperature or refrigerated

2527 C

Atropine sulfate 0.6 mg/1.5 mL WY 15 mg/1


ST 0.4 mg/1 mL ST 15 mg/1


FED 1 mg/1 mL STP, FEDh

5, 10, 20, 30 mg/1 mL

Visually compatible for up to 7 days at 23 C. (Morphine HCl tested)

2257 C

Bupivacaine HCl AST 3 mg/mL 1 mg/mL Little or no loss of either drug by HPLC in 30 days at 18 C 1932 C

k 2.5 mg/mLe

k 5 mg/mLe Physically compatible with little or no morphine or

2378 C

bupivacaine loss by HPLC in 60 days at 23 C under fluorescent light and at 4 C protected from light

k 25 mg/mLc k 5 mg/mLj

Physically compatible with little or no morphine or bupivacaine loss by HPLC in 60 days at 23 C under fluorescent light and at 4 C protected from light. Slight yellow discoloration at 23 C not indicative of decomposition

2378 C


SW BI

1.5 mg/mL 0.03 mg/mL

ES 0.2 mg/mL

Diluted to 5 mL with NS. Visually compatible with no new GC/MS peaks appearing in 1 hr at room temperature

1956 C

Butorphanol tartrate BR 4 mg/2 mL AH 15 mg/1 mL


566 C

Caffeine citrate 20 mg/1 mL SW 4 mg/1

mLVisually compatible for 4 hr at 25 C 2440 C

Chlorpromazine HCl SKF 50 mg/2

mL WY 15 mg/1 mL


PO 50 mg/2 mL STS 15 mg/1


DB 10 mg/2 mL DB ab

Discoloration develops, although no morphine loss by HPLC in 48 hr at room temperature exposed to light. Chlorpromazine not tested

1599 ?

Cimetidine HCl SKF 300 mg/2 mL WI 10 mg/1

mLPhysically compatible for 4 hr at 25 C 25 C

Clonidine HCl k 0.25 mg/mLe

k 5 mg/mLe

Physically compatible with little or no morphine or clonidine loss by HPLC in 60 days at 23 C under fluorescent light and at 4 C protected from light

2380 C

k 4 mg/mLc k 50 mg/mLj

Physically compatible with little or no morphine or clonidine loss by HPLC in 60 days at 23 C under fluorescent light and at 4 C protected from light. Slight yellow

2380 C

discoloration at 23 C not indicative of decomposition

Dimenhydrinate HR 50 mg/1 mL ST 15 mg/1


Diphenhydramine HCl PD 50 mg/1

mL WY 15 mg/1 mL


PD 50 mg/1 mL ST 15 mg/1


Droperidol MN 2.5 mg/1 mL ST 15 mg/1


Fentanyl citrate MN 0.05 mg/1 mL ST 15 mg/1


Glycopyrrolate RB 0.2 mg/1 mL LI 15 mg/1

mL

Physically compatible and pH in stability range for glycopyrrolate for 48 hr at 25 C

326 C

RB 0.2 mg/1 mL LI 30 mg/2

mL


326 C

RB 0.4 mg/2 mL LI 15 mg/1

mL


326 C

Haloperidol lactate MN 5 mg/1 mL 5 and 10 mg/1 mLc

Cloudiness forms immediately, becoming a crystalline precipitate of haloperidol and parabens

1901 I

JC 5 mg/1 mL STP, FEDh

5, 10, 20, 30 mg/1 mL


2257 C

MN 2 mg/mL ME 20 mg/mLj

White precipitate of haloperidol forms on mixing 668 I

Heparin sodium WY 100 and 200 units 1, 2, 5, 10

mg

Brought to 5 mL with sodium chloride 0.9%. Physically compatible with no morphine loss in 24 hr at 23 C

985 C

WY 100 and 200 units 1, 2, 5

mg

Brought to 5 mL with sterile water for injection. Physically compatible with no morphine loss in 24 hr at 23 C

985 C

WY 100 and 200 units

10 mg Brought to 5 mL with sterile water for injection. Immediate haze with white precipitate and 5 to 7% loss of morphine

985 I

potency

Hydroxyzine HCl PF 100 mg/4 mL WY 15 mg/1


PF 50 mg/1 mL ST 15 mg/1


PF 50 mg/ 1 mL 10 mg/

0.7 mL Physically compatible 771 C

PF 100 mg/ 2 mL 5 mg/ 0.3

mL Physically compatible 771 C

Ketamine HCl 100 mg 240 mga

Brought to 9 mL with NS. Visually compatible for 10 days refrigerated and at room temperature protected from light

1899 C

PD 1 mg/mLe SX

1 mg/mLe, 10 mg/mLe


2260 C

PD 1 mg/mLe SX 25 mg/mLe

Variable HPLC assays. 5% morphine loss in 6 days at room temperature. Up to 12 to 15% ketamine loss in 2 to 6 days may have occurred

2260 C

PD 10 mg/mLe SX 1, 10, 25 mg/mLe


2260 C

PD 25 mg/mLe SX 1, 10, 25 mg/mLe


2260 C

5, 10, 20 mg/1 mL 1 mg/1

mL

No substantial change in the concentration of either drug over 4 days

669 C

Ketamine HCl with lidocaine HCl

PD AST

2 mg/mL 2 mg/mL ES 0.2

mg/mL

Diluted to 5 mL with NS. Visually compatible with no new GC/MS peaks appearing in 1 hr at room temperature

1956 C

Meperidine HCl WI 50 mg/1 mL ST 15 mg/1

mLPhysically incompatible within 15 min 326 I

Metoclopramide HCl NO 10 mg/2

mL AH 10 mg/1 mL


565 C

DB 10 mg/2 DB ab Visually compatible with about 1599 C

mL

5% morphine loss by HPLC in 48 hr at room temperature exposed to light. Metoclopramide not tested

SKB 0.5 mg/mL EV 1 mg/mL

Diluted with NS. 5% or less loss of both drugs by HPLC in 35 days at 22 C and 182 days at 4 C followed by 7 days at 32 C

1939 C

SYO 10 mg/2 mL

STP, FEDh

5, 10, 20, 30 mg/1 mL


2257 C

RB 5 mg/mL ME 25 mg/mLj

Visually compatible with less than 10% drug loss in 7 days at 8 C

668 C

Midazolam HCl RC 5 mg/1 mL WB 10 mg/1 mL

Physically compatible for 4 hr at 25 C under fluorescent light 1145 C

RC 3 mg/mLe DB 24 mg/mLa

Visually compatible with 4.4% midazolam loss by HPLC in 13 days at 32 C. Morphine not tested

1595 C

RC 5 mg/1 mL 5 and 10 mg/1 mLc

Visually compatible with 9% or less morphine loss and 8% or less midazolam loss by HPLC in 14 days at 22 C protected from light. Subvisual microprecipitate may form, requiring filtration

1901 C

RC 5 mg/1 mL 5 and 10 mg/1 mLd

Visually compatible with 8% or less morphine loss and 3% or less midazolam loss by HPLC in 14 days at 22 C protected from light. Subvisual microprecipitate may form, requiring filtration

1901 C

Milrinone lactate STR5.25 mg/5.25 mL

WI 40 mg/5 mL

Physically compatible with no loss of either drug in 20 min at 23 C under fluorescent light

1410 C

Ondansetron HCl GW 1.33 mg/mLe ES 2.67

mg/mLe

Physically compatible with no measured increase in particulates and less than 5% loss of ondansetron and less than 4% loss of morphine by HPLC in 24 hr at 4 or 23 C

2199 C

Pantoprazole 4 mg/1 mL 50 mg/1 Yellowish precipitate 2574 I

sodium mL

Papaveretum RCi 20 mg/1 mL ST 15

mg/1mLVisually compatible for at least 15 min 326 C

Pentazocine lactate WI 30 mg/1 mL ST 15 mg/1


Pentobarbital sodium AB 500 mg/10

mL 16.2 mg/1 mL Physically compatible 55 C

WY 100 mg/2 mL WY 15 mg/1

mL Precipitate forms within 15 min 14 I

AB 50 mg/1 mL ST 15 mg/1

mLPhysically incompatible within 15 min 326 I

Prochlorperazine edisylate SKF WY 15 mg/1


PO 5 mg/1 mL ST 15 mg/1 mL


ES, SKF

10 mg/2 mL WB 10 mg/1

mL

Immediate precipitation probably due to phenol in morphine formulation

1006 I

SKF 5 mg/1 mL WY 8, 10, 15 mg/1 mL


DB 10 mg/2 mL DB ab

Discoloration develops with 22% morphine loss by HPLC in 48 hr at room temperature exposed to light. Prochlorperazine not tested

1599 I

Promazine HCl WY 50 mg/1 mL ST 15 mg/1


Promethazine HCl WY 50 mg/2 mL WY 15 mg/1


PO 50 mg/2 mL ST 15 mg/1


WY 12.5 mg WY 8 mg Cloudiness develops 98 I

Ranitidine HCl GL 50 mg/2 mL AH 10 mg/1

mL

Physically compatible for 1 hr at 25 C both macroscopically and microscopically

978 C

GW 50 mg/2 mL

STP, FEDh

5, 10, 20, 30 mg/1 mL

Visually compatible for 24 hr at 23 C. Yellow discoloration forms in 7 days. (Morphine HCl tested)

2257 C

Salbutamol GL 2.5 mg/2.5 mLf AB 5 mg/0.5

mL

Visually compatible for 1 hr both macroscopically and microscopically

1904 C

Scopolamine butylbromide

BI 20 mg/ 1 mL

STP, FEDh

5 and 10 mg/ 1 mL

Visually compatible for up to 24 hr at 23 C. (Morphine HCl

2257 C

tested)

BI 20 mg/ 1 mL

STP, FEDh

20 and 30 mg/ 1 mL


2257 C

BI 3.33 mg/mLe GRU

1.67, 5, 10 mg/mLe

Physically compatible with 4 to 6% scopolamine loss at 4 C and up to 8% loss at 23 C in 15 days. No morphine loss at either temperature in 15 days

2634 C

BI 5 mg/mLe GRU1.67, 5, 10 mg/mLe


2634 C

BI 6.67 mg/mLe GRU

1.67, 5, 10 mg/mLe


2634 C

Scopolamine butylbromide with haloperidol lactate

BI EST

5 mg/mLe 0.417 and 0.625 mg/mLe

GRU1.67, 5, 10 mg/mLe

Physically compatible with no morphine loss, about 5% haloperidol loss, and about 8% scopolamine loss at 23 C in 15 days

2700 C

BI EST

6.67 mg/mL 0.417 and 0.625 mg/mLe

GRU1.67, 5, 10 mg/mLe

Physically compatible with no morphine loss, about 5% haloperidol loss, and about 8% scopolamine loss at 23 C in 15 days

2700 C

Scopolamine HBr 0.6 mg/1.5 mL WY 15 mg/1


ST 0.4 mg/1 mL ST 15 mg/1


BP 5 mg/5 mL BPg 500 mg/5 mL

Little or no scopolamine loss by HPLC in 14 days at room temperature and 37 C. Morphine not tested

1609 C

BI 20 mg/mL FED 5 and 10 mg/1 mL

Visually compatible for up to 24 hr at 23 C. (Morphine HCl tested)

2257 C

BI 20 mg/mL STPh 5 and 10 mg/1 mL

Visually compatible for up to 24 hr at 23 C. (Morphine HCl tested)

2257 C

BI 20 mg/mL FED 20 and 30 mg/1 mL

Visually compatible for up to 7 days at 23 C. (Morphine HCl

2257 C

tested)

BI 20 mg/mL STPh 20 and 30 mg/1 mL


2257 C

Thiopental sodium AB 75 mg/3 mL LI 16.2

mg/1 mL Physically incompatible 21 I

Ziconotide acetate BB 35 mg/mL ELN 25 mcg/mL

Morphine sulfate powder dissolved in ziconotide acetate injection.l No loss of either drug by HPLC in 17 days at 5 C

2702 C

aPresent as the tartrate salt.

bAmount unspecified.

cMorphine sulfate powder dissolved in dextrose 5%.

dMorphine sulfate powder dissolved in water and sodium chloride 0.9%.

eDiluted in sodium chloride 0.9%.

fBoth preserved (benzyl alcohol 0.9%; benzalkonium chloride 0.01%) and unpreserved sodium chloride 0.9% were used as a diluent.

gTested as both sulfate and hydrochloride salts.

hTested as the hydrochloride salt.

iThe former formulation was tested.

jTested in sterile water for injection.

kExtemporaneously compounded from bulk drug powders.

lTested in polymethylpentene plastic vials to simulate syringe storage.


Morphine sulfateDrug Mfr Conc Mfr Conc Remarks Ref C/I

Acyclovir sodium BW 5 mg/mLa WB 0.08 mg/mLa


BW 5 mg/mLa AB 1 mg/mLWhite crystalline precipitate forms within 2 hr at 25 C under fluorescent light

1397 I

Aldesleukin RCs 4800 I.U./mLb SCN 1 mg/mL

Visually compatible and IL-2 activity by bioassay retained. Morphine not tested

1552 C

Allopurinol sodium BW 3 mg/mLb WI 1 mg/mLb


1686 C

Amifostine USB 10 mg/mLa AST 1 mg/mLa


1845 C

Amikacin sulfate BR 5 mg/mLa WI 1 mg/mLa


987 C

Aminophylline ES 4 mg/mLc WY 0.2 mg/mLc


Amiodarone HCl WY 4.8 mg/mLa SX 1 mg/mLa


WY 6 mg/mLa WY 1 mg/mLa


WY 6 mg/mLa WY 10 mg/mL



SEQ 0.83 mg/mLa ES 1

mg/mLaIncreased turbidity forms immediately 2117 I

Ampicillin sodium BR 20 mg/mLb WI 1 mg/mLa


987 C

Ampicillin sodium-sulbactam sodium RR 20 + 10

mg/mLb ES 1 mg/mLb


Amsacrine NCI 1 mg/mLa ES 1 mg/mLa


1381 C

Anidulafungin VIC 0.5 mg/mLa ES 15 mg/mL


2617 C

Argatroban GSK 1 mg/mLb ES 10 mg/mL


Atenolol ICI 0.5 mg/mL AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

Atracurium besylate BW 0.5 mg/mLa WY 1 mg/mLa


Atropine sulfate LY 0.4 mg/mL AST 1 mg/mLa


1706 C

Azithromycin PF 2 mg/mLb WY 1 mg/mLq

White microcrystals found upon filter inspection 2368 I

Aztreonam SQ 20 mg/mLa AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

SQ 40 mg/mLa AST 1 mg/mLa


1758 C

Bivalirudin TMC 5 mg/mLa AST 1 mg/mLa


2373 C

TMC 5 mg/mLab ES 10 mg/mL


Bumetanide RC 0.25 mg/mLAB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

Calcium chloride AB 4 mg/mLc WY 0.2 mg/mLc


Cefazolin sodium SKF 20 mg/mLa WI 1 mg/mLa


987 C

Cefepime HCl BMS 20 mg/mLa AST 1 mg/mLa

Haze forms immediately with numerous particles in 1 hr

1689 I

BMS 120 mg/mLd 1 mg/mL

Physically compatible with less than 10% cefepime loss. Morphine not tested

2513 C

Cefotaxime sodium HO 20 mg/mLa WI 1 mg/mLa


987 C

Cefotetan disodium STU 20 and 40 mg/mLa ES 1


Cefoxitin sodium MSD 20 mg/mLa WI 1 mg/mLa


987 C

MSD 40 mg/mLa ES 1 mg/mLb


Ceftazidime LIl 20 and 40 AB 1 mg/mL Physically compatible for 4 1397 C

mg/mLa hr at 25 C

GSKl 120 mg/mLd 1 mg/mL

Physically compatible with less than 10% ceftazidime loss. Morphine not tested

2513 C

Ceftizoxime sodium SKF 20 mg/mLa WI 1 mg/mLa


987 C

Ceftriaxone sodium RC 20 and 40 mg/mLa AB 1 mg/mL Physically compatible for 4

hr at 25 C 1397 C

Cefuroxime sodium GL 30 mg/mLa WI 1 mg/mLa


987 C

Chloramphenicol sodium succinate LY 20 mg/mLa WI 1

mg/mLa


987 C

Cisatracurium besylate GW 0.1, 2, 5 mg/mLa AST 1

mg/mLa


2074 C

Cisplatin BR 1 mg/mL ES 0.12 mg/mLa


1685 C

Cladribine ORT 0.015b and 0.5e mg/mL AST 1

mg/mLb


1969 C

Clindamycin phosphate UP 12 mg/mLa WI 1 mg/mLa


987 C

Cyclophosphamide MJ 10 mg/mL ES 0.12 mg/mLa


1685 C

Cytarabine UP 50 mg/mL ES 0.12 mg/mLa


1685 C

Dexamethasone sodium phosphate LY 0.2 mg/mLa AB 1 mg/mL Physically compatible for 4

hr at 25 C 1397 C

AMR 1 mg/mLa AST 1 mg/mLa


1706 C

Diazepam ES 0.5 mg/mLa AST 1 mg/mLa

Physically compatible with no change in measured haze

1706 C

or increase in particle content in 48 hr at 22 C

Digoxin BW 0.25 mg/mLAB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

Diltiazem HCl MMD 1b and 5 mg/mL SCN 15

mg/mL Visually compatible 1807 C

MMD 5 mg/mL SCN 0.4 mg/mLb Visually compatible 1807 C

MMD 1 mg/mLa SCN 2 mg/mLa


Diphenhydramine HCl SCN 2 mg/mLa AST 1 mg/mLa


1706 C

Dobutamine HCl LI 4 mg/mLa SCN 2 mg/mLa


Docetaxel RPR 0.9 mg/mLa ES 1 mg/mLa

Physically compatible with no change in measured turbidity or increase in particle content

2224 C

Dopamine HCl AB 1.6 mg/mLa AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

AB 3.2 mg/mLa SCN 2 mg/mLa


Doxorubicin HCl AD 0.2 mg/mLa ES 0.12 mg/mLa


1685 C

Doxorubicin HCl liposome injection SEQ 0.4 mg/mLa ES 1

mg/mLaPartial loss of measured natural turbidity 2087 I

Doxycycline hyclate ES 1 mg/mLa WI 1 mg/mLa


987 C

Enalaprilat MSD 0.05 mg/mLb WY 0.2

mg/mLa


1355 C

Epinephrine HCl AB 0.02 mg/mLa SCN 2

mg/mLaVisually compatible for 4 hr at 27 C 2062 C

Erythromycin lactobionate AB 5 mg/mLa WI 1

mg/mLa


987 C

Esmolol HCl DCC 1 g/100 mLf ES 15 mg/1 mL

Physically compatible when morphine is injected into Y-site of flowing admixtureg

1168 C

DCC 10 mg/mLf ES 15 Physically compatible with 1168 C

mg/mLno loss of either drug in 8 hr at ambient temperature exposed to light

Etomidate AB 2 mg/mL ES 10 mg/mL


Etoposide phosphate BR 5 mg/mLa ES 1 mg/mLa


2218 C

Famotidine MSD 0.2 mg/mLa ES 0.2 mg/mLa


MSD 0.2 mg/mLa AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

ME 2 mg/mLb 1 mg/mLa


Fenoldopam mesylate AB 80 g/mLb ES 1 mg/mLb


2467 C

Fentanyl citrate ES 0.05 mg/mLSCN 2 mg/mLa


Filgrastim AMG 30 g/mLa WY 1 mg/mLa


1687 C

Fluconazole RR 2 mg/mL IMS 25 mg/mL


RR 2 mg/mL AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

Fludarabine phosphate BX 1 mg/mLa WI 1 mg/mLa


1439 C

Foscarnet sodium AST 24 mg/mL IMS 1 mg/mLPhysically compatible for 24 hr at room temperature under fluorescent light

1335 C

AST 24 mg/mL ES 1 mg/mLc


1393 C

AST 24 mg/mL ES 5b and 15 mg/mL

Visually compatible for 24 hr at 23 C under

1529 C

fluorescent light

Furosemide ES 0.8a, 2.4a, 10 mg/mL AB 1 mg/mL

White precipitate forms within 1 hr at 25 C under fluorescent light

1397 I

AMR 10 mg/mL SCN 2 mg/mLa


Gallium nitrate FUJ 1 mg/mLb SCN 1 mg/mLb

Precipitate forms in 24 hr at 25 C 1673 I

Gemcitabine HCl LI 10 mg/mLb ES 1 mg/mLb


2226 C

Gentamicin sulfate TR 0.8 mg/mLa WI 1 mg/mLa


987 C

ES 1.2 and 2 mg/mLb ES 1


Granisetron HCl SKB 1 mg/mL AST 1 mg/mLb

Physically compatible with little or no loss of either drug by HPLC in 4 hr at 22 C

1883 C

SKB 0.05 mg/mLa AST 1

mg/mLa


2000 C

Haloperidol lactate MN 0.2 mg/mLa AST 1 mg/mLa


1706 C

Heparin sodium UP 1000 units/Lh WY 15

mg/mL


534 C

ES 50 units/mLc WY 0.2

mg/mLcPhysically compatible for 3 hr 1316 C

ES 60 units/mLa ES 1


ES 100 units/mLa SCN 2



AB 6% AST 1 mg/mLa

Physically compatible with no change in measured turbidity or increase in particle content in 4 hr at 23

2339 C

C

Hydrocortisone sodium succinate UP 10 mg/Lf WY 15

mg/mL


534 C

Hydromorphone HCl KN 1 mg/mL SCN 2 mg/mLa


Hydroxyzine HCl WI 4 mg/mLa AST 1 mg/mLa


1706 C

IL-2 RC 4800 I.U./mLb SCN 1 mg/mL

Visually compatible and IL-2 activity by bioassay retained. Morphine not tested

1552 C

Insulin, regular LI 0.2 unit/mLb ES 1


LI 0.2 unit/mLb ES 5


LI 1 unit/mLa SX 1 mg/mLa


Kanamycin sulfate BR 2.5 mg/mLa WI 1 mg/mLa


987 C

Ketorolac tromethamine WY 1 mg/mLa AST 1 mg/mLa


1706 C

Labetalol HCl SC 1 mg/mLa WY 1 mg/mLa


GL 5 mg/mL AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

GL 1 mg/mLa ES 0.5 mg/mLa

Visually compatible with little or no loss of either drug by HPLC in 4 hr at room temperature

1762 C

AH 2 mg/mLa SCN 2 mg/mLa


Levofloxacin OMN 5 mg/mLa SW 4 mg/mLVisually compatible for 4 hr at 24 C under fluorescent light

2233 C

Lidocaine HCl AB 1 mg/mLa AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

Linezolid PHU 2 mg/mL AST 1 mg/mLa

Physically compatible with no change in measured

2264 C

turbidity or increase in particle content in 4 hr at 23 C

Lorazepam WY 0.33 mg/mLb CNF 1

mg/mLiVisually compatible for 24 hr at 22 C 1855 C

WY 0.5 mg/mLa SCN 2 mg/mLa


WY 0.1 mg/mLa AST 1 mg/mLa


1706 C

Magnesium sulfate LY16.7, 33.3, 50, 100 mg/mLa

ES 1 mg/mLa


1549 C

AB 2, 4, 8 mg/mLb

j 2 mg/mLb


Melphalan HCl BW 0.1 mg/mLb WI 1 mg/mLb


1557 C

Meropenem ZEN 1 and 50 mg/mLb ES 1

mg/mLdVisually compatible for 4 hr at room temperature 1994 C

Methotrexate sodium AD 15 mg/mLk ES 0.12 mg/mLa


1685 C

Methotrimeprazine HCl LE 0.2 mg/mLa AST 1 mg/mLa


1706 C

Methyldopate HCl AMR 2.5 mg/mLa AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

Methylprednisolone sodium succinate UP 2.5 mg/mLa AB 1 mg/mL Physically compatible for 4

hr at 25 C 1397 C

Metoclopramide HCl SN 0.2 mg/mLa AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

DU 5 mg/mL AST 1 mg/mLa


1706 C

Metoprolol tartrate CI 1 mg/mL AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

Metronidazole SE 5 mg/mL WI 1 mg/mLa


987 C

Micafungin sodium ASP 1.5 mg/mLb APP 15 mg/mL

White precipitate forms immediately 2683 I

Midazolam HCl RC 0.2 mg/mLa AST 1 mg/mLa


1706 C

RC 0.1 and 0.5 mg/mLa ES 0.25

mg/mLa


1789 C

RC 0.1 and 0.5 mg/mLa ES 1

mg/mLa


1789 C

RC 5 mg/mL CNF 1 mg/mLi


RC 1 mg/mLa SX 1 mg/mLa


RC 2 mg/mLa SCN 2 mg/mLa


Milrinone lactate SW 0.2 mg/mLa SCN 2 mg/mLa


SW 0.4 mg/mLa AST 1 mg/mLa


2214 C

SS 0.2 mg/mLa FAU 25 mg/mLa


Nafcillin sodium WY 20 mg/mLa WI 1 mg/mLa


987 C

WY 30 mg/mLa ES 1 mg/mLb


Nesiritide SCI 50 mcg/mLab 15

mg/mL

Physically compatible for 4 hr but sulfite antioxidants present in some morphine sulfate productst are chemically incompatible with nesiritide

2625 ?

Nicardipine HCl WY 1 mg/mLa SCN 2 mg/mLa


DCC 0.1 mg/mLa WY 0.2 mg/mLa


Nitroglycerin AB 0.4 mg/mLa SCN 2 mg/mLa


Norepinephrine bitartrate STR 0.064

mg/mLa SX 1 mg/mLa


AB 0.128 mg/mLa SCN 2


Ondansetron HCl GL 1 mg/mLb WI 1 mg/mLa


Oxacillin sodium BE 20 mg/mLa WI 1 mg/mLa


987 C

Oxaliplatin SS 0.5 mg/mLa ES 15 mg/mL


2566 C

Oxytocin PD 0.02 unit/mLm ES 1


Paclitaxel NCI 1.2 mg/mLa WY 1 mg/mLa

Physically compatible with no change in measured turbidity in 4 hr at 22 C

1556 C

Palonosetron HCl MGI 50 mcg/mL BA 15 mg/mL

Physically compatible with no change in measured haze level or increase in particle content and no palonosetron or morphine loss

2720 C

Pancuronium bromide ES 0.05 mg/mLa WY 1

mg/mLaPhysically compatible for 24 hr at 28 C 1337 C

Pantoprazole sodium ALT 0.16 to 0.8 mg/mLb AB 1 to 10


Pemetrexed disodium LI 20 mg/mLb ES 15 mg/mL


2564 C

Penicillin G potassium PF 100,000 units/mLa WI 1

mg/mLa


987 C

Phenobarbital sodium WY 2 mg/mLa AST 1 mg/mLa


1706 C

Phenytoin sodium ES 2 mg/mLab AST 1 mg/mLa Precipitate forms after 1 hr 1706 I

Piperacillin sodium LE 60 mg/mLa WI 1 mg/mLa


987 C

Piperacillin sodium-tazobactam sodium

LE 40 + 5 mg/mLa

WY 1 mg/mLa

Physically compatible with no change in measured

1688 C

turbidity or increase in particle content in 4 hr at 22 C

Potassium chloride AB 40 mEq/Lf WY 15 mg/mL


534 C

Propofol ASZ 10 mg/mL 15 mg/mL

Precipitate formed and emulsion broke and oiled out

1916 I

ZEN 10 mg/mL AST 1 mg/mLa


2066 C

Propranolol HCl WY 1 mg/mL AB 1 mg/mL Physically compatible for 4 hr at 25 C 1397 C

Ranitidine HCl GL 0.5 mg/mLn ES 1 mg/mLb


GL 1 mg/mLa SCN 2 mg/mLa



AST 1 mg/mLa


2075 C

Sargramostim IMM 10 g/mLb WI 1 mg/mLb

Slight haze, visible with high intensity light, and small amount of particles formed in 1 hr in one of two samples

1436 I

Scopolamine HBr LY 0.05 mg/mLa AST 1

mg/mLa


1706 C

Sodium bicarbonate AB 1 mEq/mL WY 0.2 mg/mLc


Sodium nitroprusside RC 0.2 mg/mLa SX 1 mg/mLa


RC 0.3, 1.2, 3 mg/mLa AB 0.5

mg/mLr

Visually compatible for 48 hr at 24 C protected from light

2357 C

RC 1.2 and 3 mg/mLa AB 1

mg/mLr

Visually compatible for 48 hr at 24 C protected from light

2357 C

Tacrolimus FUJ 10 and 40 g/mLb

SCN 1 mg/mLb

Visually compatible with no loss of either drug by HPLC

2216 C

in 4 hr at 24 C under fluorescent light

FUJ 10 and 40 g/mLb SCN 3

mg/mLb


2216 C

Teniposide BR 0.1 mg/mLa AST 1 mg/mLa


1725 C

Thiopental sodium AB 25 mg/mL ES 10 mg/mL

White precipitate forms immediately 1801 I

AB 25 mg/mLd SCN 2 mg/mLa


Thiotepa IMMo 1 mg/mLa AST 1 mg/mLa


1861 C

Ticarcillin disodium-clavulanate potassium BE 31 mg/mLb ES 1


Tirofiban HCl ME 50 g/mLab ES 0.1 mg/mLa

Physically compatible with no loss of either drug in 4 hr at 23 C under fluorescent light

2356 C

ME 50 g/mLab ES 1 mg/mLa

Physically compatible with no loss of either drug in 4 hr at 23 C under fluorescent light

2356 C

TNA #218 to #226p ES 1 mg/mLa


2215 C

ES 15 mg/mL

Damage to emulsion integrity occurs immediately with free oil formation possible

2215 I

Tobramycin sulfate DI 0.8 mg/mLa WI 1 mg/mLa


987 C

LI 1.6, 2, 2.4 mg/mLa ES 1


TPN #131 and TPN #132p AB 1 mg/mL Physically compatible for 4

hr at 25 C 1397 C

TPN #189p DB 30 Visually compatible for 24 1767 C

mg/mL hr at 22 CTPN #203 and TPN #204p ES 1 mg/mL Visually compatible for 2 hr

at 23 C 1974 C

TPN #212 to #215p AST 1 mg/mLa


2109 C

Trimethoprim-sulfamethoxazole BW 0.8 + 4

mg/mLa WI 1 mg/mLa


987 C

Vancomycin HCl LI 5 mg/mLa WI 1 mg/mLa


987 C

Vecuronium bromide OR 0.1 mg/mLa WY 1 mg/mLa


OR 1 mg/mL SCN 2 mg/mLa


Vinorelbine tartrate BW 1 mg/mLb WI 1 mg/mLb


1558 C

Vitamin B complex with C RC 2 mL/Lf WY 15

mg/mL


534 C

Warfarin sodium DU 2 mg/mLd ES 2 mg/mLa

Visually compatible with no warfarin loss by HPLC in 30 min

2010 C

DME 2 mg/mLd ES 2 mg/mLa


Zidovudine BW 4 mg/mLa ES 1 mg/mLa


1193 C




dTested in sterile water for injection.

eTested in bacteriostatic sodium chloride 0.9% preserved with benzyl alcohol 0.9%.

fTested in dextrose 5% in sodium chloride 0.9%.

gFlowing at 1.6 mL/min.

hTested in dextrose 5% in Ringer's injection, dextrose 5% in Ringer's injection, lactated, dextrose 5%, Ringer's injection, lactated, and sodium chloride 0.9%.

iTested as the hydrochloride salt.

jExtemporaneously prepared product.

kTested in dextrose 5% with sodium bicarbonate 0.05 mEq/mL.

lSodium carbonate-containing formulation tested.

mTested in dextrose 5% in Ringer's injection, lactated.

nTested in sodium chloride 0.45%.

oLyophilized formulation tested.

pRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3-in-1 admixture, and TPN indicates a 2-in-1 admixture.

qInjected via Y-site into an administration set running azithromycin.

rTested in dextrose 5% in sodium chloride 0.2%.

sThe Roche product is a different form of IL-2 than the commercial product.

tNesiritide is incompatible with bisulfite antioxidants used in some drug formulations. The specific formulation of the product to be used should be checked to ensure that no sulfite antioxidants are present.


Multiple Drugs A seven-drug combination consisting of bupivacaine hydrochloride (Sanofi Winthrop) 1.5 mg/1 mL, clonidine hydrochloride (Boehringer Ingelheim) 0.03 mg/1 mL, fentanyl citrate (Janssen) 0.01 mg/1 mL, ketamine (Parke-Davis) 2 mg/1 mL, lidocaine hydrochloride (Astra) 2 mg/1 mL, morphine sulfate (Elkins-Sinn) 0.2 mg/1 mL, and tetracaine hydrochloride (Sanofi Winthrop) 2 mg/1 mL mixed together was found to be visually compatible with no new GC/MS peaks appearing in one hour at room temperature. (1956)

Clonidine hydrochloride (Boehringer) 30 g/mL, bupivacaine hydrochloride (Astra) 3 mg/mL, and morphine hydrochloride (Merck) 6.66 mg/mL were combined in 50-mL ambulatory infusion pump cassette reservoirs (Pharmacia Deltec). The reservoirs were stored at room temperature and protected from light for 90 days. HPLC analysis found no loss of any of the drugs. Instead, drug concentrations increased 12 to 16% during the observation period, possibly due to loss of water from the solutions. (1850)

Morphine tartrate (David Bull) 4 and 40 mg/mL was admixed with four other drugs and packaged in 10-mL polypropylene syringes with tip caps (Terumo). The formulas of the two admixtures to make 10 mL total volume are shown in Table 1. Samples were stored at 21 to 23 C and 4 to 8 C for two weeks. Most samples remained unchanged on visual inspection except Formulation 1 stored at room temperature that developed a slight straw color within 10 days. HPLC analysis found that the morphine tartrate and the other drug components except midazolam remained stable (less than 10% loss) throughout the 14-day study. Midazolam hydrochloride was also stable for 14 days under refrigeration but was only stable through 12 days in Formulation 1 and five days in Formulation 2 stored at room temperature. (2180)

Morphine hydrochloride visual compatibility in three-, four-, and five-drug combinations with five other drugs diluted in sodium chloride 0.9% was evaluated in elastomeric pump reservoirs (Baxter) when stored at 25 C and protected from light. Two series of test concentrations were evaluated for the following drugs:

Morphine hydrochloride (Grunenthal) 1.68 mg/mL with:

Dexamethasone sodium phosphate (Merck) 0.44 mg/mL

Haloperidol lactate (Esteve) 0.21 mg/mL

Metoclopramide hydrochloride 1.11 mg/mL

Midazolam hydrochloride (Roche) 0.5 mg/mL

Scopolamine butylbromide (Boehringer-Ingelheim) 1.68 mg/mL

Morphine hydrochloride (Grunenthal) 5 mg/mL with:

Dexamethasone sodium phosphate (Merck) 1.33 mg/mL

Haloperidol lactate (Esteve) 0.62 mg/mL

Metoclopramide hydrochloride 3.33 mg/mL

Midazolam hydrochloride (Roche) 1.5 mg/mL

Scopolamine butylbromide (Boehringer-Ingelheim) 5 mg/mL

All three-, four-, and five-drug combinations that contained dexamethasone sodium phosphate in addition to midazolam hydrochloride and/or haloperidol lactate resulted in immediate

precipitation, most likely free dexamethasone. All three-, four-, and five-drug combinations that did not include dexamethasone sodium phosphate and midazolam hydrochloride and/or haloperidol lactate remained visually compatible for seven days. (2701)

Table 1. Formulas of Morphine Tartrate with Multiple Drug Admixtures Tested for Stability 2180

Component Formulation 1 Formulation 2Morphine tartrate 400 mg 40 mgDexamethasone sodium phosphate 8 mg 8 mgDroperidol 2 mg 2 mgScopolamine butylbromide 20 mg 20 mgMidazolam HCl 8 mg 5 mgSodium chloride 0.9% qs to 10 mL

Bupivacaine Bupivacaine hydrochloride 25 mg/mL admixed with morphine sulfate 50 mg/mL in sterile water for injection appeared to prevent the formation of precipitation that occurs with morphine sulfate 50 mg/mL alone when refrigerated. (2378)

Bupivacaine hydrochloride 2.5 mg/mL admixed with morphine sulfate 5 mg/mL in sodium chloride 0.9% and bupivacaine hydrochloride 25 mg/mL admixed with morphine sulfate 50 mg/mL in sterile water for injection exhibited little or no loss of either drug in 60 days at 4 and 23 C. The slight yellow discoloration that appeared in the high concentration samples was not indicative of drug decomposition. Samples stored for two days at 37 C and frozen for two days at -20 C resulted in little or no loss of either drug. However, the frozen samples upon thawing exhibited the formation of large amounts of microparticulates numbering in the thousands per milliliter, possibly shed by the syringe components. (2378)

Clonidine Hydrochloride Clonidine hydrochloride (Fujisawa) 100 g/mL and morphine sulfate (Elkins-Sinn) 10 mg/mL were mixed in equal quantities, transferred to flint glass vials with rubber stoppers, and stored for 14 days at controlled room temperature protected from light. The solutions remained clear and colorless with no increase in particulate content. HPLC analysis found little or no change in concentration for either drug during the study period. (2069)

Clonidine hydrochloride 0.25 mg/mL admixed with morphine sulfate 5 mg/mL in sodium chloride 0.9% and clonidine hydrochloride 4 mg/mL admixed with morphine sulfate 50 mg/mL in sterile water for injection exhibited little or no loss of either drug at 4 and 23 C. The slight yellow discoloration that appeared in the high concentration samples was not indicative of drug decomposition. Samples stored for two days at 37 C and frozen for two days at -20 C resulted in little or no loss of either drug. However, a precipitate formed in the frozen samples as freezing occurred and in the refrigerated high concentration samples after two to four days. Upon warming to room temperature the precipitate redissolved, but the samples exhibited large amounts of undissolved microparticulates numbering in the thousands per milliliter remaining in the solutions, possibly shed by the syringe components. (2380)

References








ISBN: o ISBN-13: 978-1-58528-213-5









"M" Monographs Morphine Sulfate - AHFS 28:08.08



Ropivacaine Hydrochloride - AHFS 72:00

Products Ropivacaine hydrochloride is available in concentrations of 2 mg/mL (0.2%), 5 mg/mL (0.5%), 7.5 mg/mL (0.75%), and 10 mg/mL (1%) along with sodium chloride for isotonicity and sodium hydroxide and/or hydrochloric acid for pH adjustment in water for injection. The products are packaged in single-dose glass vials and in polypropylene plastic ampuls designed to fit Luer-lock and Luer-slip syringes. The 2-mg/mL concentration is also available in 100 and 200-mL infusion bottles. Sterile-Pak products should be selected when a container having a sterile outside is required. (1-4/06)

pH From 4 to 6.5. (404)

Tonicity Ropivacaine hydrochloride injections are isotonic. (1-4/06)

Specific Gravity The specific gravities of ropivacaine hydrochloride injections range from 1.002 to 1.005 at 25 C. (1-4/06)

Trade Name(s) Naropin

Administration Ropivacaine hydrochloride is administered parenterally by lumbar epidural injection or infusion, by thoracic epidural infusion, by injection for nerve block, and by infiltration. (1-4/06)

Stability Intact containers of ropivacaine hydrochloride should be stored at controlled room temperature. The single-dose containers have no antimicrobial preservatives. The manufacturer recommends that any remaining solution in an opened container be discarded promptly. The continuous infusion bottles should not be left in place for more than 24 hours. (1-4/06)

Autoclaving Ropivacaine hydrochloride in glass containers may be autoclaved once to sterilize the container with the drug remaining stable. (1-4/06)

/w EPDw ULLTE4N

pH Effects The solubility of ropivacaine hydrochloride is reduced above pH 6. Consequently, contact with alkaline solutions may result in precipitation. (1-4/06)



Ropivacaine HCl


Clonidine HCl BI 5 and 50 mg AZ 1 g NSa


2433 C

BI 5 mg AZ 2 g aVisually and microscopically compatible with no loss of either drug in 30 days at 30 C in the dark

2433 C

Diamorphine HCl ASZ 2 g 25 g d

No ropivacaine loss and 10% diamorphine loss in 70 days at 4 C and 28 days at 21 C

2517 C

Fentanyl citrate JN 1 mg AZ 1 g NSa


2433 C

JN 1 and 10 mg AZ 2 g a


2433 C

CUR 3 mg ASZ 1.5 g NSbcPhysically compatible with no loss of either drug in 51 days at 20 C in light or dark and refrigerated

2498 C

CUR 3 mg ASZ 1.5 g NSdPhysically compatible with no loss of either drug in 7 days at 20 C in light or dark and refrigerated

2498 C

Morphine sulfate AST 20 mg AZ 1 g NSa


2433 C

AST 20 and 100 mg AZ 2 g a


2433 C

Sufentanil citrate JN 0.4 mg AZ 1 g NSa


2433 C

JN 0.4 and 4 mg AZ 2 g a


2433 C

JC 0.5, 0.75, 1 mg ASZ 2 mg NSbd

Physically compatible with no major sufentanil loss in 96 hr at 25 C. Ropivacaine not tested

2506 C

aTested in polypropylene bags (Mark II Polybags).

bTested in glass containers.

cTested in ethylene vinyl acetate (EVA) containers.

dTested in PVC containers.


Ropivacaine HClDrug (in syringe) Mfr Amt Mfr Amt Remarks Ref C/I

Diamorphine HCl ASZ 10 g 45 mgNo ropivacaine loss with 10% diamorphine loss in 30 days at 4 C and 16 days at 21 C

2517 C

Methylprednisolone acetate PHU

80 mg/2 mL

AST 6 mg/3 mL

Little or no loss of either drug in 30 days at 4 and 24 C either exposed to or protected from light

2367 C

References






Copyright:


o © 2009 American Society of Health-System Pharmacists, Inc. All rights reserved. Database Title:

o STAT!Ref Online Electronic Medical Library ISBN:

o ISBN-13: 978-1-58528-213-5 Publication City:

o Bethesda, MD Publication Year:

o 2008 Publisher:

o American Society of Health-System Pharmacists Title:

o Handbook on Injectable Drugs - 15th Ed. (2009) Date Posted:

o 11/4/2009 4:31:06 PM CDT (UTC -05:00) Electronic Address:

o http://online.statref.com/document.aspx?fxid=141&docid=307 Date Accessed:

o 8/21/2010 4:17:27 AM CDT (UTC -05:00) Location In Title:

o HANDBOOK ON INJECTABLE DRUGS - 15th Ed. (2009) "R" Monographs Ropivacaine Hydrochloride - AHFS 72:00


CLONIDINE=CATAPRESS

Clonidine Hydrochloride - AHFS 24:08.16

Products Clonidine hydrochloride is available in concentrations of 0.1 mg/mL (100 g/mL) and 0.5 mg/mL (500 g/mL) in 10-mL vials. Each milliliter of the preservative-free solution also


contains sodium chloride 9 mg in water for injection. Hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH. (1-2/06)

pH From 5 to 7. (1-2/06)

Trade Name(s) Duraclon

Administration Clonidine hydrochloride injection is administered by continuous epidural infusion using an appropriate epidural infusion device. Clonidine hydrochloride injection must not be used with a preservative. (1-2/06)

Stability Intact vials containing the clear, colorless solution should be stored at controlled room temperature. (1-2/06) They are stable for at least six months stored at an elevated temperature of 40 C, remaining clear and colorless and exhibiting no loss of clonidine hydrochloride by HPLC analysis. (2069)

Clonidine hydrochloride (Roxane) 100 g/mL was filled into plastic syringes (Becton-Dickinson), pump medication reservoirs (Bard), and empty glass vials (Abbott) and stored at 22 to 27 C for seven days. The solution was also filled into intravenous administration set tubing (Kendall McGaw) and stored under the same conditions. In all cases, the solution remained clear and colorless and little or no loss of potency was found by HPLC analysis. (2069)

Clonidine hydrochloride 100 g/mL was delivered at a rate of 0.1 mL/hr for seven days through two epidural catheter sets, Epi-Cath (Abbott) and Port-A-Cath (Pharmacia Deltec). The temperature was maintained at 37 C with a water bath to simulate internal use of the set. The delivered clonidine hydrochloride solution remained clear and colorless throughout the study. Furthermore, the solution delivered through the Epi-Cath resulted in little or no loss by HPLC analysis. With the Port-A-Cath, a concentrating effect due to a loss of water was countered by a small clonidine hydrochloride loss of drug (about 5%). The net effect was delivery of about 95% of the clonidine hydrochloride dose. (2069)

Syringes Clonidine hydrochloride (Boehringer Ingelheim) 9 g/mL in sodium chloride 0.9% was packaged in two types of polypropylene syringes. The Omnifix (B. Braun) syringes had polyisoprene piston tips while the Terumo syringes had no natural or synthetic rubber in the product. Stored at 4, 21, and 35 C for 30 days, the test solutions in Terumo syringes exhibited no visual changes or changes in measured pH. Stored at 4, 21, and 35 C for 30 days, the test solutions in Omnifix syringes exhibited no visual changes but substantial changes in measured pH occurred in some samples. An acceptable pH was maintained for 30 days at 4 C, 5 days at 21 C, and less than 1 day at 35 C. Although the pH remained within the stability range for the drug in most of the samples, this does not definitively demonstrate stability. (2387)

Implantable Pumps An admixture of bupivacaine hydrochloride 25 mg/mL, clonidine hydrochloride 2 mg/mL, and morphine sulfate 50 mg/mL in sterile water for injection was reported to be physically and chemically stable for 90 days at 37 C in SynchroMed implantable pumps. HPLC analysis found little or no loss of any drug. (2585)



Clonidine HCl

===================================================================== Solution Mfr Mfr Conc/L Remarks Ref C/I ===================================================================== Sodium BA 200 mg Visually compatible 2359 C chloride with no loss of drug 0.9% by HPLC in 10 weeks at 37 C protected from light ---------------------------------------------------------------------


Clonidine HCl

============================================================================================================= Drug Mfr Conc/L Mfr Conc/L Test Remarks Ref C/I Soln ============================================================================================================= Baclofen 1 g 0.2 mg NS Visually compatible with no loss 2359 C of either drug by HPLC in 10 weeks at 37 C protected from light ------------------------------------------------------------------------------------------------------------- Bupivacaine HCl AST JN 1 g 35 BI 9 mg NSa Visually compatible with less 2437 C with fentanyl mg than 10% change of any drug in citrate 28 days at 4 C and 24 days at 25 C in the dark ------------------------------------------------------------------------------------------------------------- Bupivacaine HCl 25 g 50 2 g Wc Visually compatible with little 2585 C with morphine g or no loss of any drug by HPLC sulfate in 90 days at 37 C ------------------------------------------------------------------------------------------------------------- Hydromorphone 25 mg BI 150 mg c No clonidine loss in 35 days at 2593 C HCl 37 C ------------------------------------------------------------------------------------------------------------- Meperidine HCl 8 g BI 3 mg NSa Visually compatible with no loss 2710 C of either drug in 21 days at room temperature ------------------------------------------------------------------------------------------------------------- Ropivacaine HCl AZ 1 g BI 5 and 50 NSb Visually and microscopically 2433 C mg compatible with no loss of either drug in 30 days at 30 C in the dark AZ 2 g BI 5 mg b Visually and microscopically 2433 C compatible with no loss of either drug in 30 days at 30 C in the dark ------------------------------------------------------------------------------------------------------------- Ziconotide ELN 25 mg BB 2 g d Clonidine HCl powder dissolved in 2703 C acetate ziconotide acetate injection. No loss of either drug in 28 days at 37 C by HPLC ------------------------------------------------------------------------------------------------------------- aTested in PVC containers. bTested in polypropylene bags (Mark II Polybags). cTested in SynchroMed implantable pumps. dTested in SynchroMed II implantable pumps.


Clonidine HCl

======================================================================================================= Drug (in Mfr Amt Mfr Amt Remarks Ref C/I syringe) ======================================================================================================= Bupivacaine AST JN 50 mg 1.75 BI 0.45 mg Diluted to 50 mL with NS. Visually 2437 C HCl with mg compatible with less than 10% loss fentanyl of any drug in 25 days at 4 and 25 citrate C in the dark ------------------------------------------------------------------------------------------------------- Bupivacaine SW ES 1.5 mg/mL BI 0.03 mg/ Diluted to 5 mL with NS. Visually 1956 C HCl with 0.2 mg/ mL compatible with no new GC/MS peaks morphine mL in 1 hr at room temperature sulfate ------------------------------------------------------------------------------------------------------- Fentanyl JN AST 0.01 mg/mL BI 0.03 mg/ Diluted to 5 mL with NS. Visually 1956 C citrate 2 mg/mL mL compatible with no new GC/MS peaks with in 1 hr at room temperature lidocaine HCl ------------------------------------------------------------------------------------------------------- Heparin 2500 BI 0.15 mg/ Visually compatible for at least 5 1053 C sodium units/1 1 mL min mL ------------------------------------------------------------------------------------------------------- Ketamine HCl PD SW 2 mg/mL 2 BI 0.03 mg/ Diluted to 5 mL with NS. Visually 1956 C with mg/mL mL compatible with no new GC/MS peaks tetracaine in 1 hr at room temperature HCl ------------------------------------------------------------------------------------------------------- Morphine a 5 mg/mLb a 0.25 mg/ Physically compatible with little or 2380 C sulfate mLb no morphine and clonidine loss by HPLC in 60 days at 23 C under fluorescent light and at 4 C protected from light a 5 mg/mLc a 4 mg/mLc Physically compatible with little or 2380 C no morphine or clonidine loss by HPLC in 60 days at 23 C under fluorescent light and at 4 C protected from light. Slight yellow discoloration at 23 C not indicative of decomposition ------------------------------------------------------------------------------------------------------- Ziconotide ELN 25 mcg/mL BB 2 mg/mL Clonidine HCl powder dissolved in 2703 C acetated ziconotide acetate injection.d No loss of either drug in 28 days at 5 C by HPLC ------------------------------------------------------------------------------------------------------- aExtemporaneously compounded from morphine sulfate and clonidine hydrochloride powder. bTested in sodium chloride 0.9%. cTested in sterile water for injection. dTested in polymethylpentene plastic vials to simulate syringe storage.


Clonidine HCl

==================================================================================== Drug Mfr Conc Mfr Conc Remarks Ref C/I ==================================================================================== Aminophylline NYC 0.9 mg/ BI 18 mcg/ Visually 2642 C mLb mLb compatible ------------------------------------------------------------------------------------ Dobutamine HCl LI 2 mg/mLa BI 18 mcg/ Visually 2642 C mLb compatible ------------------------------------------------------------------------------------ Dopamine HCl NYC 2 mg/mLa BI 18 mcg/ Visually 2642 C mLb compatible ------------------------------------------------------------------------------------ Epinephrine HCl NYC 20 mcg/ BI 18 mcg/ Visually 2642 C mLa mLb compatible

------------------------------------------------------------------------------------ Fentanyl citrate ALP 50 mcg/mL BI 18 mcg/ Visually 2642 C mLb compatible ------------------------------------------------------------------------------------ Isoproterenol APO 4 mcg/mL BI 18 mcg/ Visually 2642 C sulfate mLb compatible ------------------------------------------------------------------------------------ Labetalol HCl GSK 1 mg/mLab BI 18 mcg/ Visually 2642 C mLb compatible ------------------------------------------------------------------------------------ Lorazepam WY 0.33 mg/ BI 0.015 mg/ Visually 1855 C mLb mL compatible for 24 hr at 22 C ------------------------------------------------------------------------------------ Magnesium BRN 9.6 mg/ BI 18 mcg/ Visually 2642 C sulfate mLa mLb compatible ------------------------------------------------------------------------------------ Midazolam HCl RC 5 mg/mL BI 0.015 mg/ Orange 1855 I mL discoloration forms in 24 hr at 22 C ALP 1 mg/mL BI 18 mcg/ Visually 2642 C mLb compatible ------------------------------------------------------------------------------------ Nitroglycerin NYC 0.4 mg/ BI 18 mcg/ Visually 2642 C mLa mLb compatible ------------------------------------------------------------------------------------ Norepinephrine APO 20 mcg/ BI 18 mcg/ Visually 2642 C bitartrate mLa mLb compatible ------------------------------------------------------------------------------------ Potassium BRN 1 mEq/mL BI 18 mcg/ Visually 2642 C chloride mLb compatible ------------------------------------------------------------------------------------ Theophylline ASZ 1 mg/mL BI 18 mcg/ Visually 2642 C mLb compatible ------------------------------------------------------------------------------------ Verapamil HCl AB 2.5 mg/mL BI 18 mcg/ Visually 2642 C mLb compatible ------------------------------------------------------------------------------------ aTested in dextrose 5%. bTested in sodium chloride 0.9%.


Baclofen Baclofen 1 mg/mL with clonidine hydrochloride 0.2 mg/mL in sodium chloride 0.9% was tested for stability over 10 weeks at 37 C protected from light in a simulation of use in an implantable pump. No loss of either drug was found and the solutions remained clear. (2359)

Bupivacaine hydrochloride Clonidine hydrochloride (Fujisawa) 100 g/mL and bupivacaine hydrochloride (Sanofi Winthrop) 7.5 mg/mL were mixed in ratios of 1:1 and 1:8 to provide final concentrations of (1:1) clonidine hydrochloride 50 g/mL and bupivacaine hydrochloride 3.75 mg/mL and (1:8) clonidine hydrochloride 11.11 g/mL and bupivacaine hydrochloride 6.67 mg/mL. The combinations were transferred to flint glass vials with rubber stoppers and stored for 14 days at controlled room temperature protected from light. The solutions remained clear and colorless with no increase in particulate content. HPLC analysis found little or no change in concentration for either drug during the study period. (2069)

Morphine Sulfate Clonidine hydrochloride (Fujisawa) 100 g/mL and morphine sulfate (Elkins-Sinn) 10 mg/mL were mixed in equal quantities and were transferred to flint glass vials with rubber stoppers and stored for 14 days at controlled room temperature protected from light. The solutions remained clear and colorless with no increase in particulate content. HPLC analysis found little or no change in concentration for either drug during the study period. (2069)

Clonidine hydrochloride 0.25 mg/mL admixed with morphine sulfate 5 mg/mL in sodium chloride 0.9% and clonidine hydrochloride 4 mg/mL admixed with morphine sulfate 50 mg/mL in sterile water for injection exhibited little or no loss of either drug in 60 days at 4 and 23 C. Slight yellow discoloration that appeared in the high concentration samples was not indicative of drug decomposition. Samples stored for two days at 37 C and frozen for two days at -20 C resulted in little or no loss of either drug. However, a precipitate formed in the frozen samples as freezing occurred and in the refrigerated high concentration samples after two to four days. Upon warming to room temperature the precipitate redissolved, but the samples exhibited large amounts of undissolved microparticulates numbering in the thousands per milliliter remaining in the solutions, possibly shed by the syringe components. (2380)

Morphine sulfate (Infumorph) 20 mg/mL with clonidine hydrochloride (Boehringer Ingelheim) 50 g/mL and morphine sulfate 2 mg/mL with clonidine hydrochloride 1.84 mg/mL were evaluated in SynchroMed EL (Medtronic) implantable pumps with silicone elastomer intrathecal catheters at 37 C for three months. No visible incompatibilities were observed and stability-indicating HPLC analysis found that delivered concentrations of both drugs were in the range of 94.0 to 99.6% of the theoretical concentrations throughout the study. Furthermore, no impairment of mechanical performance of the pump or any of its components was found. (2477)

Multiple Drugs A seven-drug combination consisting of bupivacaine hydrochloride (Sanofi Winthrop) 1.5 mg/mL, clonidine hydrochloride (Boehringer Ingelheim) 0.03 mg/mL, fentanyl citrate (Janssen) 0.01 mg/mL, ketamine hydrochloride (Parke-Davis) 2 mg/mL, lidocaine hydrochloride (Astra) 2 mg/mL, morphine sulfate (Elkins-Sinn) 0.2 mg/mL, and tetracaine hydrochloride (Sanofi Winthrop) 2 mg/mL mixed together in equal quantities was found to be visually compatible with no new GC/MS peaks appearing in one hour at room temperature. (1956)

Clonidine hydrochloride (Boehringer) 30 g/mL, bupivacaine hydrochloride (Astra) 3 mg/mL, and morphine hydrochloride (Merck) 6.66 mg/mL were combined in 50-mL ambulatory pump cassette reservoirs (Pharmacia Deltec). The reservoirs were stored at room temperature and protected from light for 90 days. HPLC analysis found no loss of any of the drugs. Instead, drug concentrations increased 12 to 16% during the observation period, possibly due to loss of water from the solutions. (1850)

References






ISBN: o ISBN-13: 978-1-58528-213-5









"C" Monographs Clonidine Hydrochloride - AHFS 24:08.16


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