WARFARIN OR COUMARIN DERIVATIVES: PROLONGATION OF PT AND ELEVATION OF INR WERE OBSERVED LEADING TO INCREASED CHANCES OF BLEEDING.
DRUGS THAT INHIBIT CYTOCHROME P450 3A4 ENZYMES
ROMIDEPSIN IS METABOLIZED BY CYP3A4. STRONG CYP3A4 INHIBITORS LIKE KETOCONAZOLE, ITRACONAZOLE, CLARITHROMYCIN, ATAZANAVIR, INDINAVIR, NEFAZODONE, NELFINAVIR, RITONAVIR, SAQUINAVIR, TELITHROMYCIN, VORICONAZOLE INCREASE CONCENTRATIONS OF ROMIDEPSIN.
DRUGS THAT INDUCE CYTOCHROME P450 3A4 ENZYMES
IN A PHARMACOKINETIC DRUG INTERACTION TRIAL WITH CO-ADMINISTERED RIFAMPIN (A STRONG CYP3A4 INDUCER), ROMIDEPSIN EXPOSURE WAS INCREASED BY APPROXIMATELY 80% AND 60% FOR AUC0-? AND CMAX, RESPECTIVELY. TYPICALLY, CO-ADMINISTRATION OF CYP3A4 INDUCERS DECREASE CONCENTRATIONS OF DRUGS METABOLIZED BY CYP3A4. THE INCREASE IN EXPOSURE SEEN AFTER CO-ADMINISTRATION WITH RIFAMPIN IS LIKELY DUE TO RIFAMPIN'S INHIBITION OF AN UNDETERMINED HEPATIC UPTAKE PROCESS THAT IS PREDOMINANTLY RESPONSIBLE FOR THE DISPOSITION OF ROMIDEPSIN.
IT IS UNKNOWN IF OTHER POTENT CYP3A4 INDUCERS (E.G., DEXAMETHASONE, CARBAMAZEPINE, PHENYTOIN, RIFABUTIN, RIFAPENTINE, PHENOBARBITAL, ST. JOHN'S WORT) WOULD ALTER THE EXPOSURE OF ROMIDEPSIN. THEREFORE, THE USE OF OTHER POTENT CYP3A4 INDUCERS SHOULD BE AVOIDED WHEN POSSIBLE.
ROMIDEPSIN IS A SUBSTRATE OF THE EFFLUX TRANSPORTER P-GLYCOPROTEIN (P-GP, ABCB1). IF ROMIDEPSIN IS ADMINISTERED WITH DRUGS THAT INHIBIT P-GP, INCREASED CONCENTRATIONS OF ROMIDEPSIN ARE LIKELY, AND CAUTION SHOULD BE EXERCISED.