diltiazem and apixaban

Pharmacokinetic interaction: Diltiazem is a moderate inhibitor of CYP3A4 and P-glycoprotein (P-gp). Apixaban is a substrate of both CYP3A4 and P-gp. Inhibition of these pathways by diltiazem reduces the metabolism and intestinal efflux of apixaban, leading to increased apixaban plasma concentrations.

Increased apixaban exposure raises the risk of bleeding, including major bleeding events such as gastrointestinal or intracranial haemorrhage. The magnitude of exposure increase depends on the diltiazem dose and formulation, and the clinical impact is significant, particularly in patients with additional risk factors for bleeding.

Avoid co-prescription where possible, or use with caution. If combined, monitor the patient closely for signs of bleeding (e.g., bruising, melaena, haematuria). Consider reducing the apixaban dose according to local guidelines or product labelling. Re-evaluate the combination if other interacting drugs or bleeding risk factors are present.

Well-established. Pharmacokinetic studies show that co-administration with diltiazem increases apixaban AUC and Cmax. Guidelines and product information recommend caution and dose adjustment with strong or moderate CYP3A4 and P-gp inhibitors.