In vitro studies have shown that R-bicalutamide is an inhibitor of CYP 3A4, with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6 activity.
Although clinical studies using antipyrine as a marker of cytochrome P450 (CYP) activity showed no evidence of a drug interaction potential with Casodex, mean midazolam exposure (AUC) was increased by up to 80%, after co-administration of Casodex for 28 days. For drugs with a narrow therapeutic index such an increase could be of relevance. As such, concomitant use of terfenadine, astemizole and cisapride is contraindicated and caution should be exercised with the co-administration of Casodex with compounds such as ciclosporin and calcium channel blockers. Dosage reduction may be required for these drugs particularly if there is evidence of enhanced or adverse drug effect. For ciclosporin, it is recommended that plasma concentrations and clinical condition are closely monitored following initiation or cessation of Casodex therapy.
Caution should be exercised when prescribing Casodex with other drugs which may inhibit drug oxidation e.g. cimetidine and ketoconazole. In theory, this could result in increased plasma concentrations of bicalutamide (Casodex) which theoretically could lead to an increase in side effects.
In vitro studies have shown that Casodex can displace the coumarin anticoagulant, warfarin, from its protein binding sites. It is therefore recommended that if Casodex is started in patients who are already receiving coumarin anticoagulants, prothrombin time should be closely monitored.
Since androgen deprivation treatment may prolong the QT interval, the concomitant use of Casodex with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de Pointes should be carefully evaluated (see Precautions).
50-mg: There is no evidence of any pharmacodynamic or pharmacokinetic interactions between Casodex and LHRH analogues.