sterile drug products used in the pain management...

Sterile Drug Products Used in the Pain Management Practice SettingPharMEDium Lunch and Learn Series

ProCE, Inc.www.ProCE.com 1

Sterile Drug Products Usedin the Pain Management Practice Setting

August 12, 2016

Featured Speaker: Stephen Jankovic, Pharm.D.

Clinical Staff PharmacistPresence Saint Joseph Medical Center

1

LUNCH AND LEARN

CE Activity Information & Accreditation

ProCE, Inc. (Pharmacist and Tech CE)

1.0 contact hour

2

Funding: This activity is self‐funded through PharMEDium.

It is the policy of ProCE, Inc. to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Dr. Jankovic has no relevant commercial and/or financial relationships to disclose.



3

Submission of an online self‐assessment and evaluation is the only way to obtain CE credit for this webinar

Go to www.ProCE.com/PharMEDiumRx

Print your CE Statement online

Live CE Deadline: September 9, 2016

CPE Monitor– CE information automatically uploaded to NABP/CPE Monitor upon

completion of the self‐assessment and evaluation (user must complete the “claim credit” step)

Online Evaluation, Self-Assessmentand CE Credit

Attendance Code

Code will be provided at the end of today’s activityAttendance Code not needed for On‐Demand

Ask a Question

Submit your questions to your site manager.

Questions will be answered at the end of the presentation.

4

Your question. . . ?



Resources

Visit www.ProCE.com/PharMEDiumRx to access:

– Handouts

– Activity information

– Upcoming live webinar dates

– Links to receive CE credit

5

Steph en Jank ovic , Ph armD

Clinical Staff Pharmacist

Pres ence Saint Jos eph Medical Center

August 12th, 2016

Sterile Drug Products Used in the Pain Management Practice Setting

6



Disclosure

I have no actual or potential conflicts of interest to disclose in relation to this presentation

PharMEDium container product offerings by drug were listed on the company website and internal documents as of the date of this presentation; however, due to ongoing revisions of container offerings, some information in this presentation may not reflect the latest container options.

7

Pharmacist Learning Objectives

Identify appropriate indications for use of sterile drug products for pain management

Compare various sterile drug products used in the pain management setting

Describe the different types of pain modalities available to patients for pain management

Evaluate potential sources of error while preparing and compounding sterile drug products

8



Pharmacy Technician Learning Objectives

Describe common indications for sterile drug products used in pain management

Identify sterile drug products used in the pain management setting

Review various routes of administration of sterile drug products used in pain management

Recognize common sources of error during the preparation of sterile drug products

9

Why Manage Pain?1

Proper pain management ‘high priority’ in US Experienced by > 100 million Americans

Cost to treat pain > half a trillion dollars

Most common reason to consult a physician

1. Use of Opioids for the Treatment of Chronic Pain: A Statement from the American Academy of Pain Management. AAPM February 2013.

10



Definition of Pain1

Defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”

Subjective in nature Varies from patient to patient

1. Pain terms: a list with definitions and notes on usage. Recommended by the IASP subcommittee on taxonomy. Pain 1979; 6:249

11

Causes of Pain1

Can be experienced at rest or related to: Surgery

Procedures

Trauma/Burns

Underlying conditions Cancer

Diabetes

Sickle Cell

1. Pain terms: A list with definitions and notes on usage. recommended by the IASP subcommittee on taxonomy. Pain 1979; 6:249

12



Challenges of Pain Management1

Subjective nature of pain Varies based on individual tolerance and underlying

conditions

Emphasis on individualized treatment for pain specialist

Requires a multimodal approach

Medications used for chronic moderate-to-severe pain often have adverse effects Risk vs. benefits assessment when choosing

treatment options

1. Use of Opioids for the Treatment of Chronic Pain: A Statement from the American Academy of Pain Management. AAPM February 2013.

13

Local/Regional Anesthetics

Buffered lidocaine

Bupivacaine

Ropivacaine (both alone and in combination with other narcotics)

Source: http://www.pharmedium.com/compounding/line/5/Pain_management/

14



Opioid Analgesics

Fentanyl

Hydromorphone

Morphine

Meperidine

Methadone


15

Combined Agents

Fentanyl-bupivacaine

Fentanyl-ropivacaine

Hydromorphone-bupivacaine

Hydromorphone-ropivacaine

Sufentanil-bupivacaine

Sufentanil-ropivacaine


16



Lidocaine HCl1

Mechanism of action Blocks initiation and conduction

of nerve impulse via decreased neuronal membrane permeability to sodium ions, resulting in inhibition of depolarization with resultant blockade of conduction

Antiarrhythmic properties as well

1. Xylocaine (lidocaine HCl injection USP) Package Insert. AAP Pharmaceuticals, LLC Schaumburg, IL. February 2010.

http://www.pharmedium.com/uploads/cms/images/Buffered-Lidocaine-Group.jpg/image-full

17

Lidocaine HCl1

Lidocaine concentration Compatible in:

1 mg/mL Sodium bicarbonate (2.4 mEq/L)

Dextrose 5% (2.4 mEq/L)

2 mg/mL Sodium bicarbonate (40 mEq/L)

1. Trissel LA. Trissel’s Stability of Compounded Formulations, 5th Edition. 2012.

Indications Local/regional anesthetic

Induction in rapid sequence intubation

Compatibility

18



Buffered Lidocaine

Containers BD syringe

Source: http://www.pharmedium.com/compounding/service/6/Buffered_Lidocaine/?lineId=2

19

Buffered Lidocaine1

Administration Intra-dermal

IV

Common adverse effects Edema

Erythema

Petechiae

Pruritus

1. Product Information: Zingo(TM) intradermal injection powder, lidocaine HCl monohydrate intradermal injection powder. Medline Industries, Inc. (per DailyMed), Mundelein, IL, 2014.

20



Why “Buffered” Lidocaine?1

Infiltration of local anesthetic can be painful Believed to be due to acidity of lidocaine HCl

Cochrane study found adjusting pH of lidocaine with sodium bicarbonate reduced pain of injection Based on 23 studies

Larger magnitude of pain decrease found in lidocaine solutions containing both sodium bicarbonate AND epinephrine vs just sodium bicarbonate

1. Cepeda MS, Tzortzopoulou A, Thackrey M, Hudcova J, Arora Gandhi P, Schumann R. Adjusting the pH of lidocaine for reducing pain on injection. Cochrane Database Syst Rev. 2010;(12): CD006581.

21

Bupivacaine HCl1

Mechanism of action Blocks generation and conduction of nerve impulses:

Increases electrical excitation threshold in the nerve

Slows propagation of the nerve impulse

Reducing the rate of rise of action potential

Progression of anesthesia determined by nerve fiber: Diameter

Myelination

Conduction velocity

1. Product Information: Marcaine(TM) Spinal solution for spinal injection, bupivacaine hydrochloride solution for spinal injection. Hospira, Inc., Lake Forest, IL, 2009.

22



Bupivacaine HCl1

Bupivacaine concentration Compatible in:

0.625 mg/mL0.6 mg/mL

0.85 mg/mL1 mg/mL

1.25 mg/mL

Sodium chloride 0.9%

0.6 mg/mL Dextrose 5%


Indications Local/regional anesthetic

Compatibility

23

Bupivacaine HCl


Baxter Intravia bags

Hospira LifeCare bag

Smiths Medication Cassette Reservoir

IFLOW On-Q Pre-filled Pain Pump

Source: http://www.pharmedium.com/compounding/service/7/Bupivacaine/?lineId=5

24



Bupivacaine HCl1

Administration Intrapleural

Epidural

Adverse Effects Bacterial meningitis

Cardiac arrest

Respiratory arrest

Seizure

1. Product Information: Marcaine(TM) Spinal solution for spinal injection, bupivacaine hydrochloride solution for spinal injection. Hospira, Inc., Lake Forest, IL, 2009.

25

Morphine Sulfate1

Mechanism of action Pure opioid agonist – activates mu-opioid receptors in central

nervous system to achieve analgesia

Decreased brain-stem respiratory response, CO2 tension, and electrical stimulation promote respiratory depression and analgesia

Induces peripheral vasodilation and opioid-induced hypotension via histamine release

1. Product Information: morphine sulfate intravenous solution, USP, morphine sulfate intravenous solution, USP. Faulding Pharmaceutical Co, Paramus, NJ, 2003.

26



Morphine Sulfate1


Compatible with virtually any solution D5W

D10W

D5LR

D5NS

D5W-1/2 NS

NS

½ NS

D5 in Ringer’s

Lactated Ringer’s injection

Ringer’s injection

27

Morphine Sulfate1

1. Altman L, Hopkins RJ, Ahmed S, et al: Stability of morphine sulfate in Cormed III (Kalex) intravenous bags. Am J Hosp Pharm: 1990. 47: 2040-2.

Concentration of 60 mg/mL in NS found to be incompatible Precipitated in 4-8 days under refrigeration

About 50% loss of drug

Discoloration occurred after 5 days at room temperature Found no loss in concentration after 14 days

Stored in Cormed II Kalex pump reservoirs

28



Morphine Sulfate, continued1

Common Indications Intractable chronic pain

Moderate to severe pain unresponsive to non-narcotic analgesics

Chest pain related to myocardial infarction

Administration IV push

Epidural

Intrathecal

PCA

1. Product Information: morphine sulfate intravenous solution, USP, morphine sulfate intravenous solution, USP. Faulding Pharmaceutical Co, Paramus, NJ, 2003.

29

Morphine Sulfate, continued


Baxter Intravia bag



Covidien monoject barrel/syringe

Source: http://www.pharmedium.com/compounding/service/34/morphine/?lineId=5

30



Morphine Sulfate, continued1

Common Adverse Effects Pruritus (epidural/intrathecal up to 80%)

Nausea (epidural/intrathecal 15-70%)

Respiratory depression

Constipation

Urinary retention (epidural/intrathecal 15-70%)

Hypotension

1. Product Information: DURAMORPH(TM) injection, morphine sulfate injection. Baxter Healthcare Corporation, Deerfield, IL, 2005.

31

Fentanyl Citrate1



Other pharmacological effects Anxiolytic/relaxation

Euphoria


Cough suppression

Reduced peristalsis of the GI system

1. Product Information: Fentanyl Citrate IV, IM injection. Hospira, Inc, Lake Forest, IL, 2008.

32



Fentanyl Citrate, continued1

Common Indications General anesthesia

Post-operative pain

Analgesia for mechanically ventilated patients

Pre-medication for procedures Ex: rapid sequence intubation

Equianalgesic dose 100 mcg = 10 mg of morphine

1. Physician’s Desk Reference Online (PDR.net): Available at: http://www.pdr.net/drug-summary/Fentanyl-Citrate-fentanyl-citrate-2474. Accessed August 10, 2016.

33


Fentanyl concentration Compatible in:

1 mcg/mL5 mcg/mL

12.5 mcg/mL20 mcg/ mL30 mcg/ mL35 mcg/mL


1 mcg/mL5 mcg/mL

20 mcg/mL40 mcg/mL

Dextrose 5%


Compatibility

34



Fentanyl Citrate, continued


Baxter Intravia bags



IFLOW On-Q Pre-filled Pain pump


Hospira PCA vial

Source: http://www.pharmedium.com/compounding/service/20/fentaNYL/?lineId=5

35


Administration IV push Continuous infusion PCA Epidural Intrathecal

Common Adverse Effects Bradycardia Hypotension Respiratory depression Constipation

1. Product Information: Fentanyl Citrate IV, IM injection, Fentanyl Citrate IV, IM injection. Hospira, Inc, Lake Forest, IL, 2008.

36



Hydromorphone HCl1



Morphine derivative 7-8 times more potent

1.5 mg = 10 mg of morphine

1. Product Information: DILAUDID(R), DILAUDID-HP(R) injection, hydromorphone hydrochloride injection. Hospira, Inc, Lake Forest, IL, 2008.

37

Hydromorphone HCl, continued1

Common Indications Moderate to severe pain in opioid-tolerant patients

Pain when opioid analgesics are appropriate


IM

PCA

Epidural

1. Product Information: hydromorphone HCl intravenous injection, intramuscular injection, subcutaneous injection. Akorn, Inc.Lake Forest, IL, 2015.

38





Compatible with D5W

D5LR

D5NS

D5W-1/2 NS

NS

½ NS

D5 in Ringer’s



39

Hydromorphone HCl, continued

Containers Baxter Intravia bag

BD syringe




Hospira PCA vial

Source: http://www.pharmedium.com/compounding/service/25/HYDROmorphone/?lineId=5

40




Common Adverse Effects Hypotension


Constipation

1. Product Information: hydromorphone HCl intravenous injection, intramuscular injection, subcutaneous injection. Akorn, Inc.Lake Forest, IL, 2015.

41

Meperidine HCl1

Mechanism of action Binds to opioid receptors in the CNS to produce analgesia and

sedative effects

NOT recommended for use as analgesic agent If used, treatment should be limited < 48 hr and dose <600

mg/hr

1. Product Information: Meperidine HCl intramuscular subcutaneous intravenous injection. West-ward Pharmaceutical Corp. Eatontown, NJ, 2011.

42



Meperidine HCl, continued1

Indications Anesthesia adjunct

Obstetric pain

Commonly used off-label for treatment of pre- and post-op shivering


Risk of drug accumulation with prolonged use

IM Approved for IM administration, but not routinely recommended

Product Information: Meperidine HCl intramuscular subcutaneous intravenous injection. West-ward Pharmaceutical Corp. Eatontown, NJ, 2011.

43



Compatible with virtually any solution D5W

D10W

D5LR

D5NS

D5W-1/2 NS

NS

½ NS

D5 in Ringer’s



44





Baxter Intravia bag



Source: http://www.pharmedium.com/compounding/service/32/Meperidine/?lineId=2

45


Common Adverse Effects Diaphoresis

Nausea/vomiting

Hypotension


1. Product Information: Meperidine HCl intramuscular subcutaneous intravenous injection. West-ward Pharmaceutical Corp. Eatontown, NJ, 2011.

46



Methadone HCl1

Mechanism of action Synthetic opioid agonist that binds to opioid receptors in the

CNS to produce analgesia and sedative effects similar to morphine

May also act as a N-methyl-D-aspartate (NMDA) receptor antagonist

1. Product Information: methadone hydrochloride intramuscular, intravenous, subcutaneous solution. aaiPharma , Wilmington, NC.

47

Methadone HCl, continued1

Common Indications Treatment of opioid dependence

Drug detoxification

Maintenance therapy

Moderate-to-severe pain refractory to non-narcotic analgesics


IM/subQ

Recommended short-term; transition to PO as soon as feasible

1. Product Information: methadone hydrochloride intramuscular, intravenous, subcutaneous solution. aaiPharma, Wilmington, NC.

48





Compatibility

Methadone concentration Compatible in:

1 mg/mL2 mg/mL5 mg/mL


49

Methadone HCl, continued


Baxter Intravia bag

Source: http://www.pharmedium.com/compounding/service/61/Methadone/?lineId=5

50




Common Adverse Effects Hypotension

Diaphoresis

Nausea/vomiting

Constipation

Prolonged QT interval


1. Product Information: methadone hydrochloride intramuscular, intravenous, subcutaneous solution. aaiPharma , Wilmington, NC.

51

Combined Epidural Agents

Fentanyl-bupivacaine

Fentanyl-ropivacaine

Hydromorphone-bupivacaine

Hydromorphone-ropivacaine

Sufentanil-bupivacaine

Sufentanil-ropivacaine


52



Benefits of Combined Agents1-2

Adequate analgesic relief with minimal motor block During labor and delivery

Adequate analgesic relief with reduced dosage need Reduced incidence of adverse effects

1. Groen RA, Bolt ML, van Kleef JW, et al. Comparison between continuous epidural infusion of bupivacaine 0.0625% plus sufentanil and bupivacaine 0.125% during labor. Reg Anesth 1992; 17(1):90.2. Elliott RD. Continuous infusion epidural analgesia for obstetrics: bupivacaine versus bupivacaine-fentanyl mixture. Can J Anaesth 1991; 38:303-310.

53

PCA Pumps1

Administration of medication controlled by patient Reduces delay in patient access to pain medication

Multiple routes of administration IV

Epidural (PCEA)

Intrathecal

Transdermal

1. Hudcova J, McNicol E, Quah C, Lau J, Carr DB. Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database Syst Rev. 2006

https://upload.wikimedia.org/wikipedia/commons/thumb/b/b4/PCA-01.JPG/800px-PCA-01.JPG

54



Fentanyl Iontophoretic Transdermal System (IONSYS®)1

First transdermal PCA Approved April 2015 for postoperative acute pain management

in the hospital

1. Source: Product Information: IONSYS® fentanyl iotophoretic transdermal system. The Medicines Company, Parsippany, NJ April 2015.

55

Fentanyl Iontophoretic Transdermal System (IONSYS®)

Source: http://www.ionsys.com/images/chart_transdermal_delivery.png

56



ON-Q® Pain Relief System

57

Balloon type pain pump: Fixed flow rate

Variable rate controller

Bolus option

1. Source: Product Information: ON-Q Pain Relief System Product Information. Kimberly-Clark Health Care Company, Roswell, GA 2010

Advantages of PCA Pumps1

Puts patients in ‘driver’s seat’ and so they can take a more active role in their pain management

Decreased risk of drug overdose Programmable doses

Dose titratability

Fixed lockout interval reduces risk of ‘too much’ and ‘too fast’

1. Hudcova J, McNicol E, Quah C, Lau J, Carr DB. Patient controlled opioid analgesia versus conventional opioid analgesia forpostoperative pain. Cochrane Database Syst Rev. 2006

58



Major Potential Sources of Error During the Compounding Process1

Product labeling

Sterile drug product preparation Gathering all required supplies

Sterile drug product compounding

Deviations in aseptic technique

1. Proceedings from the ISMP Sterile Preparation Compounding Safety Summit: Guidelines for Safe Preparation of Compounded Sterile Preparations. Institute for Safe Medication Practices 2013.

59

Potential Labeling Errors During the Compounding Process1

Wrong/missing information on label Drug name

Strengths/concentrations Ex: mg instead of mcg

Storage/stability


60



Standardized Labels1

Standardized label TALLman lettering

Drug strength/concentration

Additional safety warnings

“IV USE ONLY”

Reduces risk of mislabelingerrors

Source: http://www.pharmedium.com/uploads/cms/images/Hydromorphone_HCl_0.jpg/image-full;max$900,900.ImageHandler

61

1. Bauer DT, Guerlain S. Improving the usability of intravenous medication labels to support safe medication delivery. Int J IndErgon. 2011 Jul 1; 41(4): 394–399.

Potential Preparation/Compounding Errors1

Wrong drug Look-alike sound-alike

Wrong diluent/concentration Compatibility issues

Stability issues

Dosing issues


62



Errors in Aseptic Technique1

Contaminated product Can cause severe infection

IV/Epidural administration

Fungal meningitis outbreaks in 2012 FDA confirmed fungal and bacterial contamination in multiple

unopened vials of 3 different sterile drug products

Resulted in call for tighter regulations and FDA oversight

1. Pettit AC, Kropski JA, Castilho JL, et al. The index case for the fungal meningitis outbreak in the United States. N Engl J Med 2012;367 : 2119-2125.

63

ISMP General Recommendations1

Organizational practices comply with USP Chapter <797> standards (Level 2)

Policies and procedures that guide compounding of sterile products be well-defined (Level 3)

Organizations identify standardized workflow processes that include quality control, process change control and documentation practices (Level 3)


64



65

sterile drug products used in the pain management...

Documents