Zolpidem Fluconazole

Drugs that may affect fluconazole include cimetidine, hydrochlorothiazide, and rifampin. Drugs that may be affected by fluconazole include alfentanil, benzodiazepines, buspirone, carbamazepine, cisapride, oral contraceptives, corticosteroids, cyclosporine, haloperidol, HMG-CoA reductase inhibitors, losartan, nisoldipine, phenytoin, protease inhibitors, rifabutin, sirolimus, sulfonylureas, tacrolimus, theophylline, tolterodine, tricyclic antidepressants, vinca alkaloids, warfarin, zidovudine, and zolpidem. 

Greenblatt, D.J., von Moltke, L.L., Harmatz, J.S., Mertzais, P., Graf, J.A., Durol, A.L., Counihan, M., Roth-Schechter, B., and Shader, R.I. (1998b) Kinetic and dynamic interaction study of zolpidem with ketoconazole, itraconazole, and fluconazole. Clin Pharmacol Ther 64 661-671. 

Potential interactions of zolpidem with three commonly prescribed azole derivatives (ketoconazole, itraconazole, and fluconazole) have been evaluated in a controlled clinical study. Co-administration of zolpidem with ketoconazole impaired zolpidem clearance and enhanced its benzodiazepine-like agonist pharmacodynamic effects. Itraconazole and fluconazole had a small effect on zolpidem kinetics and dynamics. The findings were consistent with in vitro studies of differentially impaired zolpidem metabolism by azole derivatives (45). 

Zolpidem is metabolized by CYP3A. Ketoconazole 200 mg bd impaired the clearance of zolpidem 5 mg and enhanced its benzodiazepine-like pharmacodynamic effects. In contrast, itraconazole 100 mg bd and fluconazole 100 mg bd had small effects on zolpidem kinetics and dynamics (59). 

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

Fluconazole, itraconazole and ketoconazole very markedly increase the serum levels of midazolam and triazolam, thereby increasing and prolonging their sedative and amnesic effects. Similar but smaller effects are seen with itraconazole or ketoconazole and alprazolam and with itraconazole and brotizolam. Even less effect is seen with etizolam and itraconazole and no important interaction occurs between estazolam and itraconazole. Small effects are found with the non-benzodiazepine hypnotic, zolpidem, with ketoconazole and even less effects with zopiclone and itraconazole. 

No important interaction occurs between bromazepam and fluconazole, temazepam and itraconazole, zolpidem and fluconazole and probably chlordiazepoxide and ketoconazole. 

Fluconazole. In a placebo-controlled study in healthy subjects itraconazole 100 mg twice daily for 2 days had no significant effect on the pharmacokinetics of a single 5-mg dose of zolpidem given with the third dose of fluconazole. ... 

Greenblatt DJ, von Moltice LL, Harmatz JS, Mertzanis P, Graf JA, Durol ALB, Counihan M, Rotii-Schechter B, Shader RI. Kinetic and (fynamic interaction study of zolpidem witii ketoconazole, itraconazole, and fluconazole. Clin Pharmacol Ther (1998) 64, 661-71. 

Noninterfering acetaminophen, amineptine, amphotericin B, aspirin, bromazepam, buspirone, citalopram, clobazam, diazepam, didanosine, fluconazole, flunitrazepam, flu-voxamine, hydroxyitraconazole, isoniazid, itraconazole, lamivudine, loprazolam, lora-zepam, metronidazole, minalcipram, nordiazepam, omeprazole, paroxetine, pyrimethamine, rifampin, sertraline, stavudine, sulfadiazine, trimethoprim, venlafaxine, zal-citabine, zidovudine, zolpidem, zopiclone... 

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