RIFABUTIN HAS ENZYME INDUCTION PROPERTIES THAT CAN ENHANCE THE METABOLISM OF ENDOGENOUS SUBSTRATES INCLUDING ADRENAL HORMONES, THYROID HORMONES, AND VITAMIN D. RIFABUTIN CAN ALTER VITAMIN D METABOLISM. IN SOME CASES, REDUCED LEVELS OF CIRCULATING 25-HYDROXY VITAMIN D AND 1,25-DIHYDROXY VITAMIN D HAVE BEEN ACCOMPANIED BY REDUCED SERUM CALCIUM AND PHOSPHATE, AND ELEVATED PARATHYROID HORMONE. IT ACCELERATES THE METABOLISM OF THE FOLLOWING DRUGS:
ANTICONVULSANTS (EG, PHENYTOIN), ANTIARRHYTHMICS (EG, DISOPYRAMIDE, MEXILETINE,
QUINIDINE, TOCAINIDE), ORAL ANTICOAGULANTS, ANTIFUNGALS (EG, FLUCONAZOLE, ITRACONAZOLE, KETOCONAZOLE), BARBITURATES, BETA-BLOCKERS, CALCIUM CHANNEL BLOCKERS (EG, DILTIAZEM, NIFEDIPINE, VERAPAMIL), CHLORAMPHENICOL,
CORTICOSTEROIDS, CYCLOSPORINE, CARDIAC GLYCOSIDE PREPARATIONS, CLOFIBRATE, ORAL
OR OTHER SYSTEMIC HORMONE CONTRACEPTIVES, DAPSONE, DIAZEPAM, DOXYCYCLINE,
FLUOROQUINOLONES (EG CIPROFLOXACIN), HALOPERIDOL, ORAL HYPOGLYCEMIC AGENTS
(SULFONYLUREAS), LEVOTHYROXINE, METHADONE, NARCOTIC ANALGESICS, NORTRIPTYLINE,
PROGESTINS, TACROLIMUS, THEOPHYLLINE AND ZIDOVUDINE. IT MAY BE NECESSARY TO ADJUST THE DOSAGES OF THESE DRUGS IF THEY ARE GIVEN CONCURRENTLY WITH RIFABUTIN. PATIENTS USING ORAL OR OTHER SYSTEMIC HORMONAL CONTRACEPTIVES SHOULD BE ADVISED TO CHANGE TO NONHORMONAL METHODS OF BIRTH CONTROL DURING RIFABUTIN THERAPY.
RIFABUTIN HAS BEEN OBSERVED TO INCREASE THE REQUIREMENTS FOR ANTICOAGULANT DRUGS
OF THE COUMARIN TYPE. IN PATIENTS RECEIVING ANITCOAGULANTS AND RIFABUTIN CONCURRENTLY, IT IS RECOMMENDED THAT THE PROTHROMBIN TIME BE PERFORMED DAILY OR AS FREQUENTLY AS NECESSARY TO ESTABLISH AND MAINTAIN THE REQUIRED DOSE OF ANTICOAGULANT. DIABETES MAY BECOME MORE DIFFICULT TO CONTROL. CONCURRENT USE OF KETOCONAZOLE AND RIFABUTIN HAS RESULTED IN DECREASED SERUM CONCENTRATIONS OF BOTH DRUGS. CONCURRENT USE OF RIFABUTIN AND ENALAPRIL HAS RESULTED IN DECREASED CONCENTRATIONS OF ENALAPRILAT, THE ACTIVE METABOLITE OF ENALAPRIL. CONCOMITANT ANTACID ADMINISTRATION MAY REDUCE THE ABSORPTION OF RIFABUTIN. DAILY DOSES OF RIFABUTIN SHOULD BE GIVEN AT LEAST 1 HOUR BEFORE THE INGESTION OF ANTACIDS. PROBENECID AND COTRIMOXAZOLE HAVE BEEN REPORTED TO INCREASE THE BLOOD LEVEL OF RIFABUTIN. WHEN RIFABUTIN IS GIVEN CONCOMITANTLY WITH EITHER HALOTHANE OR ISONIAZID, THE POTENTIAL FOR HEPATOTOXICITY IS INCREASED. PLASMA CONCENTRATIONS OF SULFAPYRIDINE MAY BE REDUCED FOLLOWING THE CONCOMITANT ADMINISTRATION OF SULFASALAZINE AND RIFABUTIN. THIS FINDING MAY BE THE RESULT OF ALTERATION IN THE COLONIC BACTERIA RESPONSIBLE FOR THE REDUCTION OF SULFASALAZINE TO SULFAPYRIDINE AND MESALAMINE.
PLASMA CONCENTRATIONS OF RIFABUTIN ARE INCREASED BY CLARITHROMYCIN (AND POSSIBLY OTHER MACROLIDES) OR FLUCONAZOLE, RESULTING IN INCREASED RIFABUTIN TOXICITY, IN PARTICULAR UVEITIS AND NEUTROPENIA.
ANTIRETROVIRAL DRUGS.
RIFABUTIN INTERACTS WITH HIV-PROTEASE INHIBITORS LIKE INDINAVIR, AMPRENAVIR, ATAZANAVIR, FOSAMPRENAVIR, LOPINAVIR-RITONAVIR, NELFINAVIR, OR RITONAVIR, OR THE NNRTIS EFAVIRENZ OR NEVIRAPINE RESULTING IN REDUCTIONS IN PLASMA CONCENTRATIONS OF THE HIV-PROTEASE INHIBITOR AND INCREASES IN RIFABUTIN PLASMA CONCENTRATIONS, WITH A POSSIBLE RISK OF UVEITIS. DOSE MODIFICATIONS ARE REQUIRED FOR RIFABUTIN IN SOME COMBINATIONS AND SHOULD BE SUBSTANTIAL (150 MG EVERY OTHER DAY OR THREE TIMES EACH WEEK) WHEN IT IS GIVEN WITH ATAZANAVIR, LOPINAVIR-RITONAVIR, OR RITONAVIR IN PARTICULAR. RIFABUTIN SHOULD NOT BE GIVEN WITH DELAVIRDINE OR SAQUINAVIR ALONE; HOWEVER, SAQUINAVIR MAY BE GIVEN WITH RIFABUTIN IF RITONAVIR IS ALSO GIVEN. INCREASES IN DOSES OF INDINAVIR AND NELFINAVIR ARE ALSO REQUIRED.