Voriconazole Rifampicin

RIFAMPICIN, RIFABUTIN, RIFAPENTINE ITRACONAZOLE, KETOCONAZOLE, POSACONAZOLE, VORICONAZOLE i levels of these azoles, with significant risk of therapeutic failure. Rifampicin is a very potent inducer that can produce undetectable concentrations of ketoconazole Rifampicin is a powerful inducer of CYP3A4 and other CYP isoenzymes. Rifabutin is a less powerful inducer but more potent than rifapentine. Rifapentine is an inducer of CYP3A4 and CYP2C8/9. Rifampicin is also a powerful inducer of P-gp, thus 1 bioavailability of itraconazole Avoid co-administration of ketoconazole or voriconazole with these drugs. Watch for inadequate therapeutic effects of itraconazole. Higher doses of itraconazole may not overcome this interaction, so consider the use of less lipophilic fluconazole, which is less dependent on CYP metabolism. Avoid co-administration of posaconazole with rifabutin... 

Clinically important, potentially hazardous interactions with amiodarone, astemizole, bepridil, carbamazepine, chloroquine, cisapride, clarithromycin, dihydroergotamine, disopyramide, ergotamine, grapefruit juice, halofantrine, haloperidol, itraconazole, ketoconazole, methadone, moxifloxacin, phenobarbital, phenytoin, pimozide, procainamide, quinidine, rifampicin, ritonavir, sotalol, St John s wort, telithromycin, terfenadine, voriconazole... 

Rifampicin markedly reduces voriconazole levels, and the combination should be avoided. Posaconazole is predicted to be similarly affected. 

The manufacturer notes that rifampicin 600 mg once daily decreased the maximum plasma levels and AUC of voriconazole 200 mg twice daily by about 95%. Even doubling the dose of voriconazole did not give adequate exposure. The concurrent use of voriconazole and rifampicin is therefore contraindicated. ... 

Rifampicin increases the metabolism of the azote antifungals by the liver. However, as fluconazole (unlike ketoconazole, itraconazole and voriconazole) is mainly excreted unchanged in the urine, changes to its metabolism would not be expected to have as marked an etfect as on these other azotes. 

The manufacturer predicts that posaconazole levels may be significantly lowered when used with rifampicin. They suggest that the combination be avoided unless the benefit to the patient outweighs the risk. Voriconazole levels are very markedly reduced by rifampicin and concurrent use is contraindicated. ... 

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