R-bicalutamide has been shown in vitro to be an inhibitor of CYP3A4 activity, with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6. Exercise caution when giving bicalutamide concomitantly with midazolam (a CYP 3A4 substrate) since midazolam Cmax and AUC have been shown to increase 1.5 and 1.9 fold, respectively, in clinical trials.
Bicalutamide displaces warfarin (coumarin anticoagulant) from its protein binding site in vitro. Close monitoring of prothrombin time is therefore recommended in patients who are already receiving coumarin anticoagulants.
Although no pharmacodynamic or pharmacokinetic interaction exists between bicalutamide and LHRH agonists, bicalutamide may prevent the harmful clinical consequences of flare associated with LHRH agonist therapy.
Co-administration of ciclosporin and calcium channel blockers with bicalutamide may theoretically increase bicalutamide's plasma concentrations. Evidence of enhanced or adverse drug effect may warrant dose reduction and close monitoring of patients after initiation or cessation of bicalutamide.
Drugs which inhibit drug oxidation such as cimetidine and ketoconazole may theoretically increase plasma concentrations of bicalutamide which may result in increased side effects.
Concomitant administration with alcohol should be avoided to prevent facial flushing during bicalutamide therapy.