Genitourinary hemorrhage associated with coadministration of dabigatran and amiodarone: a case report

Purpose: To describe a genitourinary hemorrhage associated with co-administration of amiodarone, a P-glycoprotein (P-gp) inhibitor, and dabigatran, a P-gp substrate, and to review the published literature on the topic. P-glycoprotein is a plasma membrane transport protein that functions as an efflux pump in the gastrointestinal tract (GIT), kidneys, liver and brain. In the GIT, P-gp transports drugs from the cell membrane to the gut lumen. P-gp inhibition leads to increased plasma concentrations of P-gp substrates.  We report a 76 year-old male who presented to the hospital in atrial fibrillation, with rapid ventricular response. Upon admission, a genitourinary hemorrhage was discovered.  Current outpatient medications included amiodarone 400 mg TID for rhythm control and dabigatran 150mg BID for stroke prevention.  The patient’s PTT, PT and INR were elevated upon admission. His CrCl was 59 ml/min. Dabigatran was held and the patient received blood products, but not hemodialysis. Eventually the dabigatran was restarted and the patient was discharged home on dabigatran 150 mg BID and amiodarone 400 mg daily.

Methods: We performed a MEDLINE search (1946 - June 2012) using keywords dabigatran, amiodarone and p-glycoprotein.

Results: We found no published case reports of interactions between amiodarone and dabigatran. Pharmacokinetics studies reported that P-gp inhibition of dabigatran by amiodarone leads to increases in AUC ranging from 12 – 60%. Currently the US package labeling does not recommend dose adjustments for concurrent use of dabigatran and amiodarone in patients with normal renal function. According to the European Medicines Agency, however, concomitant administration of dabigatran and amiodarone requires decreased dabigatran dosing when used for postoperative thromboprophylaxis.

Conclusion: This is among the first published case reports of a hemorrhage associated with co-administration of dabigatran and amiodarone in a patient with normal renal function. Caution and clinical judgment must be used when using these agents in combination.