Key result
Concomitant use of p-glycoprotein inhibitors increases dabigatran levels, warranting a dose reduction to 75 mg twice daily for patients with moderate renal impairment taking dronedarone or ketoconazole.
Why the study?
What are the pharmacokinetic interactions and clinical relevance of co-administering dabigatran with p-glycoprotein inhibitors or antithrombotics?
What are the pharmacokinetic interactions and clinical relevance of co-administering dabigatran with p-glycoprotein inhibitors or antithrombotics?
While many p-glycoprotein inhibitors increase dabigatran levels without apparent clinical relevance, dose reduction is advised when co-administering with dronedarone or ketoconazole in patients with moderate renal impairment.
May inform dosing caution with dronedarone or ketoconazole in moderate renal impairment; leaves open prospective outcome validation.
p-glycoprotein inhibitors Dronedarone 70%-100% increase No apparent clinical relevance Ketoconazole 38%-53% increase No apparent clinical relevance Verapamil Variable depending on timing No apparent clinical relevance Amiodarone 58% increase Effects mitigated by enhanced renal clearance Quinidine 53% increase No apparent clinical relevance Antithrombotics Clopidogrel 30% increase No change in clotting studies for either medication Enoxaparin No change No effects on clotting studies Data derived from the dabigatran package insert. For patients taking dronedarone and systemic ketoconazole with moderate renal impairment (CrCl 30 -50 mL/min), consider reducing dabigatran dose to 75 mg twice daily.
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Alberts et al. (2011) conducted a review in Stroke. Dabigatran was evaluated. Concomitant use of p-glycoprotein inhibitors increases dabigatran levels, warranting a dose reduction to 75 mg twice daily for patients with moderate renal impairment taking dronedarone or ketoconazole.
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