Skip to content
My WebMD Sign In, Sign Up
Endodan

Interactions

Alfentanil; Fentanyl; Oxycodone/Selected CYP3A4 Inhibitors

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Serious. These medicines may interact and cause very harmful effects. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

Your other medicine may slow down how quickly your liver processes your pain medicine.

What might happen:

The amount of pain medicine in your blood may increase and you may become more drowsy than normal.

What you should do about this interaction:

Let your healthcare professionals (e.g. doctor or pharmacist) know that you are taking these medicines together. Your doctor may want to adjust the dose of your medicine.If you feel more sleepy or tired than normal, contact your healthcare professional as soon as possible.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

References:

1.Actiq (fentanyl citrate) Australian prescribing information. Orphan Australia Pty Ltd. November 2, 2002.

2.Duragesic (fentanyl) US prescribing information. Janssen Pharmaceuticals, Inc. July, 2012.

3.OxyContin (oxycodone hydrochloride) US prescribing information. Perdue Pharma L.P. July, 2012.

4.Liukas A, Hagelberg NM, Kuusniemi K, Neuvonen PJ, Olkkola KT. Inhibition of cytochrome P450 3A by clarithromycin uniformly affects the pharmacokinetics and pharmacodynamics of oxycodone in young and elderly volunteers. J Clin Psychopharmacol 2011 Jun;31(3):302-8.

5.Bartkowski RR, Goldberg ME, Larijani GE, Boerner T. Inhibition of alfentanil metabolism by erythromycin. Clin Pharmacol Ther 1989 Jul; 46(1):99-102.

6.Feierman DE, Lasker JM. Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. Role of CYP3A4. Drug Metab Dispos 1996 Sep;24(9):932-9.

7.Palkama VJ, Isohanni MH, Neuvonen PJ, Olkkola KT. The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil. Anesth Analg 1998 Jul; 87(1):190-4.

8.Palkama VJ, Neuvonen PJ, Olkkola KT. The CYP 3A4 inhibitor itraconazole has no effect on the pharmacokinetics of i.v. fentanyl. Br J Anaesth 1998 Oct;81(4):598-600.

9.Saari TI, Gronlund J, Hagelberg NM, Neuvonen M, Laine K, Neuvonen PJ, Olkkola KT. Effects of itraconazole on the pharmacokinetics and pharmacodynamics of intravenously and orally administered oxycodone. Eur J Clin Pharmacol 2010 Apr;66(4):387-97.

10.Kummer O, Hammann F, Moser C, Schaller O, Drewe J, Krahenbuhl S. Effect of the inhibition of CYP3A4 or CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Eur J Clin Pharmacol 2011 Jan;67(1):63-71.

11.Samer CF, Daali Y, Wagner M, Hopfgartner G, Eap CB, Rebsamen MC, Rossier MF, Hochstrasser D, Dayer P, Desmeules JA. The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone. Br J Pharmacol 2010 Jun;160(4):907-18.

12.Samer CF, Daali Y, Wagner M, Hopfgartner G, Eap CB, Rebsamen MC, Rossier MF, Hochstrasser D, Dayer P, Desmeules JA. Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. Br J Pharmacol 2010 Jun; 160(4):919-30.

13.Klees TM, Sheffels P, Dale O, Kharasch ED. Metabolism of alfentanil by cytochrome p4503a (cyp3a) enzymes. Drug Metab Dispos 2005 Mar; 33(3):303-11.

14.Lalovic B, Phillips B, Risler LL, Howald W, Shen DD. Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos 2004 Apr;32(4):447-54.

15.Olkkola KT, Palkama VJ, Neuvonen PJ. Ritonavir's role in reducing fentanyl clearance and prolonging its half-life. Anesthesiology 1999 Sep; 91(3):681-5.

16.Nieminen TH, Hagelberg NM, Saari TI, Neuvonen M, Neuvonen PJ, Laine K, Olkkola KT. Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir. Eur J Clin Pharmacol 2010 Oct;66(10):977-85.

17.Norvir (ritonavir) Australian prescribing information. Abbott Australasia Pty. Ltd. January 29, 2004.

18.Gronlund J, Saari T, Hagelberg N, Martikainen IK, Neuvonen PJ, Olkkola KT, Laine K. Effect of telithromycin on the pharmacokinetics and pharmacodynamics of oral oxycodone. J Clin Pharmacol 2010 Jan; 50(1):101-8.

19.Kharasch ED, Walker A, Hoffer C, Sheffels P. Intravenous and oral alfentanil as in vivo probes for hepatic and first-pass cytochrome P450 3A activity: noninvasive assessment by use of pupillary miosis. Clin Pharmacol Ther 2004 Nov;76(5):452-66.

20.Kharasch ED, Whittington D, Hoffer C. Influence of hepatic and intestinal cytochrome P4503A activity on the acute disposition and effects of oral transmucosal fentanyl citrate. Anesthesiology 2004 Sep;101(3):729-37.

21.Tateishi T, Krivoruk Y, Ueng YF, Wood AJ, Guengerich FP, Wood M. Identification of human liver cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation. Anesth Analg 1996 Jan;82(1):167-72.

22.Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT. Voriconazole, but not terbinafine, markedly reduces alfentanil clearance and prolongs its half-life. Clin Pharmacol Ther 2006 Nov;80(5):502-8.

23.Saari TI, Laine K, Neuvonen M, Neuvonen PJ, Olkkola KT. Effect of voriconazole and fluconazole on the pharmacokinetics of intravenous fentanyl. Eur J Clin Pharmacol 2008 Jan;64(1):25-30.

24.Hagelberg NM, Nieminen TH, Saari TI, Neuvonen M, Neuvonen PJ, Laine K, Olkkola KT. Voriconazole drastically increases exposure to oral oxycodone. Eur J Clin Pharmacol 2009 Mar;65(3):263-71.

25.Bartkowski RR, McDonnell TE. Prolonged alfentanil effect following erythromycin administration. Anesthesiology 1990 Sep;73(3):566-8.

26.Horton R, Barber C. Opioid-induced respiratory depression resulting from transdermal fentanyl-clarithromycin drug interaction in a patient with advanced COPD. J Pain Symptom Manage 2009 Jun;37(6):e2-5.

27.Hallberg P, Marten L, Wadelius M. Possible fluconazole-fentanyl interaction-a case report. Eur J Clin Pharmacol 2006 Jun;62(6):491-2.

28.Mercadante S, Villari P, Ferrera P. Itraconazole-fentanyl interaction in a cancer patient. J Pain Symptom Manage 2002 Sep;24(3):284-6.

29.Watanabe M, Homma M, Momo K, Okoshi Y, Wada T, Hara A, Chiba S, Kohda Y. Effects of voriconazole co-administration on oxycodone-induced adverse events: a case in the retrospective survey. Eur J Clin Pharmacol 2011 Jan 8.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, expect as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

More about Drugs and Medications

URAC: Accredited Health Web Site HONcode Seal AdChoices