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Nizoral

Interactions

Itraconazole; Ketoconazole/Selected Benzodiazepines

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:

Severe. These medicines may interact and cause very harmful effects and are usually not taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

When these two medicines are taken together, your body may not process your anxiety or sleeping medicine properly.

What might happen:

You may experience unwanted drowsiness, dizziness, confusion, or slow reflexes.

What you should do about this interaction:

Contact your healthcare professionals (e.g. doctor or pharmacist) as soon as possible about taking these two medicines together. They may already be aware of this interaction and may be monitoring you for it. It may be necessary to adjust the dose of your anxiety or sleeping medicine. Do not start, stop, or change the dosage of any medicine before checking with them first.

References:

1.Xanax (alprazolam) US prescribing information. Pharmacia & Upjohn Company August, 2011.

2.Prosom (estazolam) US prescribing information. Abbott Laboratories January, 2004.

3.Sporanox (itraconazole) US prescribing information. Janssen Pharmaceutica Products, L.P. June, 2014.

4.Halcion (triazolam) US prescribing information. Pharmacia & Upjohn Company December, 2008.

5.Versed Syrup (midazolam hydrochloride) US Prescribing Information. Roche Pharmaceuticals December, 1998.

6.Versed Injection (midazolam hydrochloride) US prescribing information. Roche Pharmaceuticals June 2000.

7.Yasui N, Kondo T, Otani K, Furukori H, Kaneko S, Ohkubo T, Nagasaki T, Sugawara K. Effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam. Psychopharmacology (Berl) 1998 Oct;139(3):269-73.

8.Greenblatt DJ, Wright CE, von Moltke LL, Harmatz JS, Ehrenberg BL, Harrel LM, Corbett K, Counihan M, Tobias S, Shader RI. Ketoconazole inhibition of triazolam and alprazolam clearance: differential kinetic and dynamic consequences. Clin Pharmacol Ther 1998 Sep;64(3):237-47.

9.Allqvist A, Miura J, Bertilsson L, Mirghani RA. Inhibition of CYP3A4 and CYP3A5 catalyzed metabolism of alprazolam and quinine by ketoconazole as racemate and four different enantiomers. Eur J Clin Pharmacol 2007 Feb; 63(2):173-9.

10.von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Harmatz JS, Shader RI. Inhibitors of alprazolam metabolism in vitro: effect of serotonin- reuptake-inhibitor antidepressants, ketoconazole and quinidine. Br J Clin Pharmacol 1994 Jul;38(1):23-31.

11.Otsuji Y, Okuyama N, Aoshima T, Fukasawa T, Kato K, Gerstenberg G, Miura M, Ohkubo T, Sugawara K, Otani K. No effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of estazolam. Ther Drug Monit 2002 Jun;24(3):375-8.

12.Miura M, Otani K, Ohkubo T. Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam. Xenobiotica 2005 May;35(5):455-65.

13.Backman JT, Kivisto KT, Olkkola KT, Neuvonen PJ. The area under the plasma concentration-time curve for oral midazolam is 400-fold larger during treatment with itraconazole than with rifampicin. Eur J Clin Pharmacol 1998 Mar;54(1):53-8.

14.Ahonen J, Olkkola KT, Neuvonen PJ. Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers. Br J Clin Pharmacol 1995 Sep;40(3):270-2.

15.Olkkola KT, Ahonen J, Neuvonen PJ. The effects of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth Analg 1996 Mar;82(3):511-6.

16.Olkkola KT, Backman JT, Neuvonen PJ. Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 1994 May;55(5):481-5.

17.Wang JS, Wen X, Backman JT, Taavitsainen P, Neuvonen PJ, Kivisto KT. Midazolam alpha-hydroxylation by human liver microsomes in vitro: inhibition by calcium channel blockers, itraconazole and ketoconazole. Pharmacol Toxicol 1999 Oct;85(4):157-61.

18.von Moltke LL, Greenblatt DJ, Schmider J, Duan SX, Wright CE, Harmatz JS, Shader RI. Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. J Clin Pharmacol 1996 Sep;36(9):783-91.

19.Lam YW, Alfaro CL, Ereshefsky L, Miller M. Pharmacokinetic and pharmacodynamic interactions of oral midazolam with ketoconazole, fluoxetine, fluvoxamine, and nefazodone. J Clin Pharmacol 2003 Nov; 43(11):1274-82.

20.Stoch SA, Friedman E, Maes A, Yee K, Xu Y, Larson P, Fitzgerald M, Chodakewitz J, Wagner JA. Effect of different durations of ketoconazole dosing on the single-dose pharmacokinetics of midazolam: shortening the paradigm. J Clin Pharmacol 2009 Apr;49(4):398-406.

21.Tham LS, Lee HS, Wang L, Yong WP, Fan L, Ong AB, Sukri N, Soo R, Lee SC, Goh BC. Ketoconazole renders poor CYP3A phenotype status with midazolam as probe drug. Ther Drug Monit 2006 Apr;28(2):255-61.

22.Patki KC, Von Moltke LL, Greenblatt DJ. In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Drug Metab Dispos 2003 Jul;31(7):938-44.

23.Takano M, Hasegawa R, Fukuda T, Yumoto R, Nagai J, Murakami T. Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells. Eur J Pharmacol 1998 Oct 9; 358(3):289-94.

24.Wrighton SA, Ring BJ. Inhibition of human CYP3A catalyzed 1'-hydroxy midazolam formation by ketoconazole, nifedipine, erythromycin, cimetidine, and nizatidine. Pharm Res 1994 Jun;11(6):921-4.

25.Neuvonen PJ, Varhe A, Olkkola KT. The effect of ingestion time interval on the interaction between itraconazole and triazolam. Clin Pharmacol Ther 1996 Sep;60(3):326-31.

26.Varhe A, Olkkola KT, Neuvonen PJ. Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 1994 Dec;56(6 Pt 1):601-7.

27.von Moltke LL, Greenblatt DJ, Harmatz JS, Duan SX, Harrel LM, Cotreau-Bibbo MM, Pritchard GA, Wright CE, Shader RI. Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors and clinical confirmation of a predicted interaction with ketoconazole. J Pharmacol Exp Ther 1996 Feb;276(2):370-9.

28.Nizoral (ketoconazole oral) US prescribing information. Janssen Pharmaceuticals February, 2014.

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.

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