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.
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.
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. April, 2012.
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.
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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.
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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.
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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.