apixaban and clarithromycin

Pharmacokinetic interaction: clarithromycin inhibits both CYP3A4 and P-glycoprotein (P-gp). Apixaban is a substrate of CYP3A4 and P-gp, so this inhibition reduces apixaban metabolism and efflux, leading to increased plasma concentrations.

Increased apixaban exposure raises the risk of bleeding, which can be severe or life-threatening. Patients may experience bruising, haematoma, gastrointestinal bleeding, or intracranial haemorrhage.

Avoid co-prescription if possible. If combined use is essential, reduce the apixaban dose (for example, from 5 mg twice daily to 2.5 mg twice daily) and monitor the patient closely for signs of bleeding. Do not use this combination in patients already taking apixaban 2.5 mg twice daily. Consider alternative antibiotics that are not strong CYP3A4/P-gp inhibitors.

The interaction is well established, based on pharmacokinetic studies and product labelling. Clarithromycin is a recognised strong inhibitor of CYP3A4 and P-gp, and apixaban prescribing information includes dose reduction guidance for concomitant use with such inhibitors.