Injectable Drugs

Propofol-®Lipuro 10 mg/ml and 20 mg/ml

Go for the original – Lipuro®-Technology by B. Braun

B. Braun Melsungen AG | Hospital Care | 34209 Melsungen | GermanyTel. +49 5661 71-0 | www.bbraun.com X. 00.00.00/0 Nr. 000 0000A

Propofol-®Lipuro 1% (10 mg/ml)Propofol-®Lipuro 2% (20 mg/ml)CompositionPropofol-®Lipuro 1% (10 mg/ml)1 ml emulsion for injection or infusion contains 10 mg Propofol.Excipients: Soya-bean oil, re� ned, medium-chain triglycerides, glyce-rol, egg lecithin, sodium oleate, water for injections.Propofol-®Lipuro 2% (20 mg/ml)1 ml emulsion for injection or infusion contains 20 mg Propofol.Excipients: Soya-bean oil, re� ned, medium-chain triglycerides, glyce-rol, egg lecithin, sodium oleate, water for injections.Therapeutic indicationsPropofol-Lipuro 10 mg/ml is a short-acting intravenous general anaes-thetic for- induction and maintenance of general anaesthesia in adults and children > 1 month- sedation of ventilated patients >16 years of age in the intensive care unit- sedation for diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia in adults and children > 1 month. Propofol-Lipuro 20 mg/ml is a short-acting intravenous general anaes-thetic for- induction and maintenance of general anaesthesia in adults and children > 3 years- sedation of ventilated patients >16 years of age in the intensive care unit- sedation for diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia in adults and children > 3 years.ContraindicationsPropofol-Lipuro 10 mg/ml and Propofol-Lipuro 20 mg/ml are contrain-dicated in patients with a known hypersensitivity to propofol or to any of the excipients.Propofol-Lipuro 10 mg/ml and Propofol-Lipuro 20 mg/ml containing soya-bean oil and should not be used in patients who are hypersensitive to peanut or soya.Propofol-Lipuro 10 mg/ml and Propofol-Lipuro 20 mg/ml must not be used in patients of 16 years of age or younger for sedation for intensive care.

Special warnings and precautions for usePropofol should be given by those trained in anaesthesia (or, where appropriate, doctors trained in the care of patients in Intensive Care).Patients should be constantly monitored and facilities for mainte-nance of a patent airway, arti� cial ventilation, oxygen enrichment and other resuscitative facilities should be readily available at all times. Propofol should not be administered by the person conducting the diagnostic or surgical procedure.Undesirable e� ectsInduction and maintenance of anaesthesia or sedation with propofol is generally smooth with minimal evidence of excitation. The most commonly reported ADRs are pharmacologically predictable side ef-fects of an anaesthetic/sedative agent, such as hypotension. The na-ture, severity and incidence of adverse events observed in patients receiving propofol may be related to the condition of the recipients and the operative or therapeutic procedures being undertaken.Immune system disorders Very rare: Anaphylaxis – may include angioedema, bronchospasm, erythema and hypotensionMetabolism and Nutritional disorder Frequency not known (Not known as it cannot be estimated from the available clinical trial data.): Metabolic acidosis, hyperkalaemia, hy-perlipidaemiaPsychiatric disorders Frequency not known: Euphoric mood, drug abuse (Drug abuse, predo-minantly by health care professionals.)Nervous system disorders Common: Headache during recovery phaseRare: Epileptiform movements, including convulsions and opisthotonus during induction, maintenance and recoveryVery rare: Postoperative unconsciousnessFrequency not known: Involuntary movementsCardiac disorders Common: Bradycardia (Serious bradycardias are rare. There have been isolated reports of progression to asystole.)Very rare: Pulmonary oedemaFrequency not known: Cardiac arrhythmia, cardiac failure, (Rapidly progressive cardiac failure (in some cases with fatal outcome) in adults. The cardiac failure in such cases was usually unresponsive to inotropic supportive treatment.)Vascular disorders Common: Hypotension (Occasionally, hypotension may require use of intravenous � uids and reduction of the administration rate of propofol.)

Uncommon: Thrombosis and phlebitisRespiratory, thoracic and mediastinal disordersCommon: Transient apnoea during inductionGastrointestinal disordersCommon: Nausea and vomiting during recovery phaseVery rare: PancreatitisHepatobiliary disordersFrequency not known: HepatomegalyMusculoskeletal and connective tissue disordersFrequency not known: Rhabdomyolysis (Very rare reports of rhabdo-myolysis have been received where propofol has been given at doses greater than 4 mg/kg/hr for ICU sedation.)Renal and urinary disorders Very rare: Discolouration of urine following prolonged administrationFrequency not known: Renal failureReproductive system and breast Very rare: Sexual disinhibitionGeneral disorders and administration site conditionsVery common: Local pain on induction (May be minimised by using the larger veins of the forearm and antecubital fossa. With Propofol-®Lipuro local pain can also be minimised by the co-administration of lidocaine.)InvestigationsFrequency not known: Brugada type ECGInjury, poisoning and procedural complicationsVery rare: Postoperative feverCombinations of rhabdomyolysis, metabolic acidosis, hyperkalaemia, hyperlipidaemia, hepatomegaly, renal failure and cardiac failure, re-ported as “Propofol infusion syndrome”, may be seen in seriously ill patients who often have multiple risk factors for the development of the events.For prescription only!Version 10/2011Marketing authorization holderB. Braun Melsungen AGCarl-Braun-Straße 1D-34212 Melsungen, Germany

See local Prescribing Information for full details, as Prescribing Information may vary from country to country.

ProductTotal

VolumeContainer

TypeSales Unit

Propofol-®Lipuro 10 mg/ml

200 mg/ 20 mlGlass

Ampoule 5 x 20 ml

200 mg/ 20 mlSingle Dose Glass Vial

10 x 20 ml

500 mg/ 50 mlSingle Dose Glass Vial

10 x 50 ml

1000 mg/100 mlSingle Dose Glass Vial

10 x 100 ml

ProductTotal

VolumeContainer

TypeSales Unit

Propofol-®Lipuro 20 mg/ml

1000 mg/50 mlSingle Dose Glass Vial

10 x 50 ml

Injectable Drugs

Lipuro®-Technology

Technology & Innovation: Propofol-®Lipuro is a highly innovative product from B. Braun’s unique Lipuro®-Technology, which uses MCT/LCT lipid emulsion as the drug delivery base with excellent solubility and stability.

Clinical approval: Since its launch in 1999, Propofol-®Lipuro has been administered to millions of patients in over 120 countries. Data from clinical studies have published in scores in prestigious medical journals.

Setting standards: Propofol-®Lipuro sets standards that inspire imitators. The clini-cal bene� ts of MCT/LCT are superior to LCT or MCT emulsions. To date, Propofol-®Lipuro remains the only formulation proven to reduce pain on injection.

Service continuity: In line with our slogan „Sharing Expertise“, Propofol-®Lipuro is further proof of B. Braun’s continued commitment to patients and doctors, hospital and community.

There is only one Propofol-®Lipuro. Go for the original.

Propofol-®Lipuro 10 mg/ml

Signi� cant reduction of injection pain

Rapid onset and quick recovery

Excellent anesthesia control

Propofol-®Lipuro 20 mg/ml

Reduced lipid and � uid load

Improved lung function

Enhanced liver function

Sustained immune function

Clinical bene� ts of innovation

There is only one Propofol-®Lipuro. Go for the original.

Injectable Drugs

Propofol-®Lipuro 10 mg/ml

Minimum pain. Maximum comfort.Local pain on propofol injection is a well-known problem inanesthesiology, especially in pediatric settings. Compared toconventional LCT or MCT emulsions, Propofol-®Lipuro has beenformulated with 30 % less free propofol in the aqueous phase (a).The result is a signi� cant reduction in pain at the injection site.

Fig. 1: Signi� cantly reduced injection pain. Adapted from (b).

60

50

40

30

20

10

0

% of Patients

37 % 64 %

12

10

8

6

4

2

0

0% 10.7%

% of Patients

Fig. 2: Signi� cantly reduced sensitivity to severe pain. Adapted from (c).

Proven clinical bene� tsB. Braun applied its over 30 years‘ experience with lipid emulsions in combining Lipuro®-Technology with propofol. The result, Propofol-®Lipuro 20 mg/ml is an anesthetic with outstanding safety and good tolerability. It is ideally suited for patients re-quiring long-term sedation.

Fig. 4: MCT/LCT lipid emulsion sustains immune function. Adapted from (e).

Fig. 3: MCT/LCT lipid emulsion shortens ventilation period. Adapted from (d).

15

10

5

0

days

p<0.05

10 14

90

80

70

60

50

40

0

% killed bacteria

67.4%79.9%

day 2day 0

79.4%76.3%

day 2day 0

p<0.05

a) Müller RH, Harnisch S. Physico chemical characterization of propofol-loaded emulsions and interaction with plasma proteins. Eur Hosp Pharm 2000; 6: 24-31

b) Larsen B, Beerhalter U, et al. Less pain on injection by a new formulation of propofol? A comparison with propofol LCT. Anaesthesist 2001; 50(11): 842-5

c) Rau J, Roizen MF, et al. Propofol in an emulsion of long- and medium-chain triglycerides: the e� ect on pain. Anesth Analg 2001; 93(2): 382-4

d) Marsili I, Iovinelli G, et al. Parenteral nutrition in COPD patients: long vs. medium- chain triglycerides (MCT). Clinical Nutrition 1992; 11: 45, special supplement

e) Waitzberg DL, Bellinati-Pires R, et al. E� ect of total parenteral nutrition with di� erent lipid emulsions on human monocyte and neutrophil funcions.

Nutrition 1997; 13: 128-132

Severe pain reported on questioningOverall incidence of pain on injection Ventilation period in COPD patients Neutrophils cell activity

Propofol-®Lipuro 20 mg/ml

Propofol-®Lipuro Propofol-®Lipuro Propofol-LCT MCT/LCT emulsion LCT emulsion MCT/LCT emulsion LCT emulsionPropofol-LCT

Injectable Drugs

26. Rochette A, Avoiding propofol injection pain in

children: a prospective, randomized, double-

blinded, placebo-controlled study BJA 2008

27. Soltész S, E� ect of a 0.5% Dilution of Propofol

on Pain on Injection during Induction of

Anesthesia in Children,

Anesthesiology 2007; 106:80-4

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the incidence of moderate to severe local pain

induced by the main dose;

Acta Anesthesiol Scand 2007; 521: 460-463

18. Krobbuaban B, Does Addition of Lidocaine to

Medium- and Long-Chain Triglyceride Propofol

Emulsions Signi� cantly Reduce Pain on Injection?

J Med Assoc Thai 2008; 91 (3): 383-7

19. Sethi N, Prevention of Propofol Pain: A

Comperative Study,

M.E.J. Anesth 20 (1), 2009, 71-74

Propofol-®Lipuro: Continuously pioneer

1984Lipofundin® MCT/LCTFirst MCT/LCT emulsionis developed

1999Propofol-®Lipuro 10 mg/ml - First propofol in MCT/LCT emulsion is launched

Literature on ...Reduction of injection pain

Pediatric patients

Facilitated lipid metabolism

Improved lung function

Enhanced liver function

Sustained immune function

28. Lünstedt B, Deltz E, et al. Randomisierte Studie

zum Vergleich zwischen langkettigen (LCT)

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therapie.

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nutrition using conventional and mediumchain

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triglycerides and long-term parenteral

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TPN and liver dysfunction. Clinical Nutrition

1989; 8: 31, special supplement

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um and long-chain triglycerides on lymphocytes

subpopulations and functions in patients with

acquired immunode� ciency syndrome:

a prospective study. JPEN 1998; 22: 67-71

39. Waitzberg DL, Bellinati-Pires R, et al. E� ect of

total parenteral nutrition with di� erent lipid

emulsions on human monocyte and neutrophil

functions.

Nutrition 1997; 13: 128-132

Injectable Drugs

Lipuro®-Technology: Perfectly documented

2002Propofol-®Lipuro 10 mg/ml - First propofol for induction and maintenance of anesthesia in children one month or older

2001Propofol-®Lipuro 20 mg/mlFirst Propofol 20 mg/ml inMCT/LCT emulsion is introduced

2012Propofol-®Lipuro is marketed in > 120 countries

1. Larsen B, Beerhalter U, et al. Less pain on

injection by a new formulation of propofol?

A comparison with propofol LCT.

Anaesthesist 2001; 50(11): 842-5

2. Rau J, Roizen MF, et al. Propofol in an

emulsion of long- and medium-chain

triglycerides: the e� ect on pain.

Anesth Analg 2001; 93(2): 382-4

3. Bachmann-Mennenga B, Ohlmer A, et al.

Incidence of pain after intravenous injection of

a medium-/long-chain triglyceride

emulsion of propofol. An observational study

in 1375 patients.

Arzneimittelforschung 2003; 53(9): 621-6

7. Liljeroth E, Akeson J. Less local pain on

intravenous infusion of a new propofol

emulsion.

Acta Anaesthesiol Scand 2005; 49(2): 248-51

8. Nagao N, Uchida T, et al. Medium-/long-chain

triglyceride emulsion reduced severity of pain

during propofol injection.

Can J Anaesth 2005; 52(6): 660-1

9. Nishiyama T. How to decrease pain at

rapid injection of propofol: e� ectiveness of

� urbiprofen.

J Anesth 2005; 19(4): 273-6

14. Yew WS, Chong SY, et al. The e� ects of

intravenous lidocaine on pain during

injection of medium-and long-chain

triglyceride propofol emulsions.

Anesth Analg 2005; 00(6): 1693-5

15. Ozawa A, Isono M, et al. Comparison of

propofol LCT and propofol MCT/LCT regarding

the injection pain at di� erent sites and the

memory.

Masui 2005; 54 (11): 1241-6

16. Elliot SC, Mallick A, et al. A prospective

randomised double-blind comparison of

propofol®Lipuro vs propofol with or without

lidocaine: e� ect on injection pain.

Anesthesia 2006; 61: 81-2

4. Kam E, Abdul-Latif MS, et al. Comparison of

Propofol-Lipuro with propofol mixed with

lidocaine 10 mg on propofol injection pain.

Anaesthesia 2004; 59(12): 1167-9

5. Kunitz O, Losing R, et al. Propofol-LCT versus

propofol-MCT/LCT with or without lidocaine:

a comparison on pain on injection.

Anasthesiol Intensivmed Notfallmed

Schmerzther 2004; 39(1): 10-4

6. Auerswald K, Pfei� er F, et al. Pain on injection

with propofol. Anasthesiol Intensivmed

Notfallmed Schmerzther 2005; 40(5): 259-66

10. Ohmizo H, Obara S, et al. Mechanism of

injection pain with long and long-medium

chain triglyceride emulsive propofol.

Can J Anaesth 2005; 52(6): 595-9

11. Sun NC, Wong AY, et al. A comparison of

pain on intravenous injection between two

preparations of propofol.

Anesth Analg 2005; 101(3): 675-8

12. Yamakage M, Iwasaki S, et al. Comparative

study between propofol in a long-chain

triglyceride and propofol in a medium/long-

chain triglyceride during sedation with

targetcontrolled infusion.

Anaesth Intensive Care 2005; 33(3): 351-5

13. Yamakage M, Iwasaki S, et al. Changes

in concentrations of free propofol by

modi� cation of the solution.

Anesth Analg 2005; 101(2): 385-8

20. Bresson JL, Narcy P, et al. Energy substrate

competition: comparative study of LCT and

MCT utilization during continuos TPN in

infants.

Clinical Nutrition 1986; 5, 54, Special

supplement

21. Lai HS, Chen WJ. E� ects of medium and

long-chain triacylglycerols in pediatric surgical

patients.

Nutrition 2000; 16: 401-406

22. Larsen R, Beerhalter U, et al. Propofol in a new

formulation (Propofol MCT/LCT): E� ect on

injection pain in children.

A comparison with Propofol-LCT Anaesthesist,

2001; 50: 676-678

23. Angsten G, Boberg M, et al. Metabolic e� ects

in neonates receiving intravenous medium-

chain triglycerides.

Acta Paediatr 2002; 91: 188-197

24. Donnell SC, Lloyd DA, et al. The metabolic

response to intravenous medium-chain

triglycerides in infants after surgery.

J. Pediatr 2002;141:689-694

25. Menci RA. A comparative study on e� ects of

lipid emulsions in neonatal TPN.

Clinical Nutrition 2004; 23: 906

31. Marsili I, Iovinelli G, et al. Parenteral

nutritionin COPD patients: long vs. medium-

chain triglycerides (MCT).

Clinical Nutrition 1992; 11: 45, special

supplement

32. Smyrniotis VE, Kostopanagiotou GG, et al.

Long-chain versus medium-chain lipids in

acute pancreatitis complicated by acute

respiratory distress syndrome: e� ects on

pulmonary hemodynamics and gas exchange.

Clinical Nutrition 2001; 20:1 39-143

33. Faucher M, Bregeon F, et al. Cardiopulmonary

e� ects of lipid emulsions in patients with

ARDS.Chest 2003; 124: 285-291

34. Theilen HJ, Adam S, et al. Propofol in a

Medium-Long-Chain Triglyceride Emulsion:

Pharmcological Characteristics and Potential

Bene� cial E� ects.

Anesth Analg 2002; 95: 923-9

2008Propofol-Lipuro 5 mg/mlFirst Propofol 5 mg/ml in MCT/LCT emulsion is introduced