Rifabutin Posaconazole

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... 

Rifabutin levels are increased by fluconazole, posaconazole, voriconazole, and possibly itraconazole. Patients taking this combination are at increased risk of rifabutin toxicity, specifically uveitis, and should be closely monitored. Rifabutin markedly reduces the plasma levels of itraconazole, posaconazole, and voriconazole. These azoles should be used cautiously with rifabutin, if at all Rifabutin does not affect the metabolism of fluconazole. 

In a study in healthy subjects the concurrent use of posaconazole 200 mg once daily and rifabutin 300 mg once daily for 10 days increased the AUC of rifabutin by 72% and decreased the AUC of posaconazole by 51 % when compared with either drug alone."... 

Rifabutin increases the metabolism of itraconazole, posaconazole and voriconazole, probably, at least in part, by inducing their metabolism by the cytochrome P450 CYP3A subfamily. Fluconazole is largely excreted unchanged in the urine and so it is not affected. The azoles apparently increase rifabutin levels by inhibiting its metabolism, probably by CYP3A4. Raised rifabutin levels can cause uveitis. 

On the basis of the interaction between rifabutin and posaconazole, the manufacturer suggests that the combination be avoided unless the benefit to the patient outweighs the risk. If the combination is used, monitor the efficacy of posaconazole and the toxicity of rifabutin, particularly full blood counts and uveitis. 

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