Amiodarone × Dabigatran

Amiodarone inhibits P-glycoprotein (P-gp), the efflux transporter for dabigatran. After a single 600 mg dose of amiodarone, dabigatran AUC rose about 1.6-fold and Cmax about 1.5-fold (EMA SmPC). Because amiodarone has a long half-life, the effect may persist for weeks after it is stopped.

Gum bleeding, epistaxis, bruising without trauma, black stools, blood in urine. Risk is higher in renal impairment.

After elective hip or knee replacement, reduce dabigatran for thromboprophylaxis to 150 mg once daily (two 75 mg capsules); the EMA SmPC requires this for all patients on amiodarone. In atrial fibrillation and in treatment of deep vein thrombosis and pulmonary embolism, amiodarone does not call for a dose change (EMA SmPC; for atrial fibrillation also the FDA label). At creatinine clearance (CrCl) 30–50 mL/min, choose 110 mg twice daily individually based on bleeding risk (EMA SmPC). The FDA label says to avoid P-gp inhibitors at CrCl below 50 mL/min in deep vein thrombosis, pulmonary embolism and after hip replacement. Dabigatran is contraindicated at CrCl below 30 mL/min (EMA SmPC). Keep watching for signs of bleeding and anaemia for several weeks after amiodarone is stopped.