Alfentanil; Fentanyl; Oxycodone/Selected Antifungals (mono deleted 03/15/2012)
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:
Some antifungals 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; have trouble breathing or have slow or shallow breathing; have a slow heartbeat; have cold/clammy skin; feel faint, dizzy, confused, or cannot think/walk/talk normally; have a seizure; or have hallucinations, 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.Duragesic (fentanyl) US prescribing information. Janssen Pharmaceuticals, Inc. July, 2012.
2.OxyContin (oxycodone hydrochloride) US prescribing information. Perdue Pharma L.P. July, 2012.
3.Vfend (voriconazole) UK summary of product characteristics. Pfizer Limited March 25, 2008.
4.Vfend (voriconazole) US prescribing information. Pfizer November, 2010.
5.Sporanox (itraconazole) US prescribing information. Janssen Pharmaceutica Products, L.P. April, 2012.
6.Nizoral (ketoconazole) US prescribing information. Janssen Pharmaceutica, Inc. February, 2002.
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.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.
9.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.
10.Mercadante S, Villari P, Ferrera P. Itraconazole-fentanyl interaction in a cancer patient. J Pain Symptom Manage 2002 Sep;24(3):284-6.
11.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.
12.Hallberg P, Marten L, Wadelius M. Possible fluconazole-fentanyl interaction-a case report. Eur J Clin Pharmacol 2006 Jun;62(6):491-2.
13.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.
14.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.
15.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.
16.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.
17.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.
18.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.
19.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.
20.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.
