Coumarin Anticoagulants: Potentiation of coumarin-type anticoagulant effects has been observed with prolongation of the prothrombin time (PT)/International normalized ratio (INR). Exercise caution when coumarin-type anticoagulants are given together with fenofibrate. Reduce dosage of the anticoagulant to maintain the PT/INR at the desired level to prevent bleeding complications. Frequent PT/INR determinations are advisable until it has been definitely determined that PT/INR has stabilized.
Immunosuppressants (e.g., ciclosporin, tacrolimus): Since renal excretion is the primary elimination route of fibrate drugs including fenofibrate, concomitant administration of nephrotoxic immunosuppressants such as ciclosporin and tacrolimus, may result in deterioration of renal function. The benefits and risks of using fenofibrate with immunosuppressants and other potentially nephrotoxic agents should be carefully considered, and the lowest effective dose employed and renal function monitored.
HMG-CoA Reductase Inhibitors (Statins): The combined use of fenofibrate and statins should be avoided unless the benefit of further alterations in lipid levels is likely to outweigh the increased risk of this drug combination. The combined use of fibric acid derivatives and HMG-CoA reductase inhibitors has been associated, in the absence of marked pharmacokinetic interaction, in numerous case reports, with rhabdomyolysis, markedly elevated creatinine kinase levels and myoglobinuria, leading in a high proportion of cases to acute renal failure. The use of fibrates alone, including fenofibrate, may occasionally be associated with myositis, myopathy, or rhabdomyolysis. Patients receiving fenofibrate and complaining of muscle pain, tenderness, or weakness should have prompt medical evaluation for myopathy, including serum creatinine kinase level determination. Discontinue fenofibrate therapy if myopathy/myositis is suspected or diagnosed.
Bile Acid Sequestrants: Because of their potential binding effects, bile acid sequestrants may decrease absorption of fenofibrate when administered concurrently. Fenofibrate should be administered 1 hour before or 4 to 6 hours after a bile acid sequestrant.
Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrate coadministered with colchicine. Exercise caution when these drugs are used concomitantly.
Glitazones: Cases of reversible paradoxical reduction of HDL-C have been reported during concomitant administration of fenofibrate and glitazones. Monitor HDL-C levels. Discontinue either therapy when HDL-C is too low.