Zopiclone Itraconazole

Antifungal imidazoles (ketoconazole, itraconazole, and analogues) compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22, 39, 41-43). 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

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. 

Itraconazole 200 mg daily or a placebo was given to 10 healthy young subjects for 4 days. On day 4 they were also given a single 7.5-mg oral dose of zopiclone. The itraconazole increased the maximum plasma levels of the zopiclone by 29% (from 49 to 63 nanograms/mL), increased its AUC by 73%, and prolonged its half-life from 5 to 7 hours. But despite these increases, there were no statistical or clinical differences between the performance of the psychomotor tests carried out during the placebo and itraconazole phases of the study. 

The effects of itraconazole on temazepam or zopiclone and ketoconazole on chlordiazepoxide or zolpidem are small and seem unlikely to be clinically significant in most patients. 

Jalava K-M, Olkkola KT, Neuvonen PJ. Effect of itraconazole on tiie pharmacokinetics and pharmacod3mamics of zopiclone. EurJ ClinPharmacol (1996) 51, 331-4. 

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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