Rifabutin with itraconazole

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... 

HIV infection (in combination with other antiretrovirals) PO 800 mg (two 400-mg capsules) q8h. Dosage adjustments when given concomitantly Delavirdine, itraconazole, ketoconazok Reduce dose to 600 mg q8h. Efavirenz-. Increase dose to 1,000 mg q8h. Lopinavir/ritonavir Reduce dose to 600 mg twice a day. Nevirapine-. Increase dose to 1,000 mgqSh. Rifabutin-. Reduce rifabutin by lA and increase indinavir to 1,000 mg q8h. Ritonavir 100-200 mg twice a day and indinavir 800 mg twice a day or ritonavir 400 mg twice a day and indinavir 400 mg twice a day. 

Since indinavir is a substrate as well as an inhibitor of CYP3 A4, numerous and complex drug interactions can occur as described above. Indinavir levels decrease with concurrent use of rifabutin, fluconazole, St. John s wort, and rifampin. Caution is advised with other 3 A4 inducers also, including phenobarbital, phenytoin, carbamezepine, and dexamethasone. Dose reduction of indinavir should be considered if coadministered with delavirdine, ketoconazole, or itraconazole, while an increase in the dose of indinavir is indicated if the drug is coadministered with efavirenz or rifabutin. 

Clinically important, potentially hazardous interactions with amiodarone, anabolic steroids, antithyroid agents, barbiturates, bivalirudin, cimetidine, clofibrate, clopidogrel, cyclosporine, delavirdine, dextrothyroxine, disulfiram, fluconazole, glutethimide, imatinib, itraconazole, ketoconazole, metronidazole, miconazole, penicillins, phenylbutazones, piperacillin, quinidine, quinine, rifabutin, rifampin, rifapentine, rofecoxib, salicylates, sulfinpyrazone, sulfonamides, testosterone, thyroid, zileuton... 

Clinically important, potentially hazardous interactions with amiodarone, atorvastatin, bepridil, carbamazepine, delavirdine, dihydroergotamine, etravirine, flecainide, itraconazole, ketoconazole, lidocaine, lopinavir, lovastatin, midazolam, phenobarbital, phenytoin, pimozide, propafenone, quinidine, rifabutin, rifampin, sildenafil, simvastatin, St John s wort, triazolam, vardenafil, warfarin... 

Clinically important, potentially hazardous interactions with atazanavir, carbamazepine, clarithromycin, CYP3A4 inhibitors, dexamethasone, grapefruit juice, indinavir, itraconazole, nefazodone, nelfinavir, phenobarbital, phenytoin, rifabutin, rifampin, rifapentin, ritonavir, saquinavir, St John s wort, telithromycin, voriconazole. The concomitant use of strong CYP3A4 inducers should be avoided... 

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. 

Sm ith JA, Hardin TC, I tterson TF, Rinaldi MG, Graybill JR. Rifabutin (RIF) decreases itraconazole (ITRA) plasma levels in patients with HIV-infectioa Am Soc Microbiol 2nd Nat Conf Human retroviruses and related infecticxis. Washii ton DC, Jan 29—Feb 2 1995, 77. 

Lefort A, Launay O, Carbon C. Uveitis associated with rifabutin proii ylaxis and itraconazole therapy. Ann Intern Med 996) 125,939-40. 

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