MYOPATHY AND RHABDOMYOLYSIS (WITH OR WITHOUT ACUTE RENAL FAILURE) HAVE BEEN REPORTED WHEN ANOTHER HMG-COA REDUCTASE INHIBITOR WAS USED IN COMBINATION WITH IMMUNOSUPPRESSIVE DRUGS, GEMFIBROZIL, ERYTHROMYCIN, OR LIPID-LOWERING DOSES OF NICOTINIC ACID. CONCOMITANT THERAPY WITH HMG-COA REDUCTASE INHIBITORS AND THESE AGENTS IS GENERALLY NOT RECOMMENDED. FLUVASTATIN IS METABOLISED MAINLY BY THE CYTOCHROME P450 ISOENZYME CYP2C9 AND DOES NOT HAVE THE SAME INTERACTIONS WITH ENZYME INHIBITORS AS SIMVASTATIN, ALTHOUGH CAUTION HAS BEEN ADVISED WHEN SUCH COMBINATIONS ARE USED. HOWEVER, USE WITH RIFAMPICIN, A CYP2C9 INDUCER, MAY REDUCE THE BIOAVAILABILITY OF FLUVASTATIN BY ABOUT 50%. CONCOMITANT ADMINISTRATION OF FLUVASTATIN AND PHENYTOIN INCREASED THE LEVELS OF PHENYTOIN AND FLUVASTATIN. CONCOMITANT ADMINISTRATION OF IMMEDIATE- RELEASE FLUVASTATIN SODIUM WITH CIMETIDINE, RANITIDINE AND OMEPRAZOLE RESULTS IN A SIGNIFICANT INCREASE IN THE FLUVASTATIN CMAX (43%, 70% AND 50%, RESPECTIVELY) AND AUC (24%-33%), WITH AN 18%-23% DECREASE IN PLASMA CLEARANCE. USE WITH RIFAMPICIN RESULTS IN SIGNIFICANT REDUCTION IN CMAX (59%) AND AUC (51%), WITH A LARGE INCREASE (95%) IN PLASMA CLEARANCE.