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Oral Anticoagulants: Fenofibrate enhances oral anticoagulant effect and may increase risk of bleeding. It is recommended that the dose of anticoagulants is reduced by about ⅓ at the start of treatment and then gradually adjusted if necessary according to international normalize ratio (INR) monitoring. Therefore, this combination is not recommended.
Cyclosporin: Some severe cases of reversible renal function impairment have been reported during concomitant administration of fenofibrate and cyclosporin. The renal function of these patients must therefore, be closely monitored and the treatment with fenofibrate stopped in the case of severe alternation of laboratory parameters.
HMG-CoA Reductase Inhibitors and Other Fibrates: The risk of serious muscle toxicity is increased if a fibrate is used concomitantly with HMG-CoA reductase inhibitors or other fibrates. Such combination therapy should be used with caution and patients monitored closely for signs of muscle toxicity.
Cytochrome P-450 Enzymes: In vitro using human liver microsomes indicate that fenofibrate and fenofibric acid are not inhibitors of cytochrome (CYP) 450 isoforms CYP3A4, CYP2D6, CYP2E1 or CYP1A2. They are weak inhibitors of CYP2C19 and CYP2A6 and mild to moderate inhibitors of CYP2C9 at therapeutic concentrations.
Patients co-administered fenofibrate and CYP2C19, CYP2A6 and especially CYP2C9 metabolised drugs with a narrow therapeutic index should be carefully monitored and if necessary dose adjustment of these drugs is recommended.
