dabigatan

Dabigatan, also known as dabigatran etexilate, is an oral anticoagulant that acts as a direct thrombin inhibitor. It is administered as the prodrug dabigatan etexilate and is converted in the body to the active compound, dabigatran.

Medical uses: It reduces the risk of stroke and systemic embolism in adults with nonvalvular atrial fibrillation; it treats deep vein thrombosis and pulmonary embolism; and it serves as venous thromboembolism prophylaxis after hip or knee replacement in certain regimens.

Mechanism: Dabigatan directly inhibits thrombin (factor IIa), blocking the conversion of fibrinogen to fibrin and thereby reducing clot formation. It affects both circulating and clot-bound thrombin, contributing to its anticoagulant effect.

Administration and pharmacokinetics: Administered orally as the prodrug, which is converted to active dabigatan in the body. It has relatively low oral bioavailability, is largely cleared by the kidneys, and has a half-life in adults of about 12 to 17 hours. Dosing is tailored to the indication and to renal function.

Safety and interactions: The drug increases bleeding risk and interacts with P-glycoprotein inhibitors and certain NSAIDs and other anticoagulants. It is contraindicated in active major bleeding, severe renal impairment, and in patients with mechanical heart valves. It is generally avoided in pregnancy and lactation; elderly patients may require more careful monitoring.

Reversal and management of bleeding: For major bleeding or urgent reversal, idarucizumab (Praxbind) can rapidly neutralize dabigatran’s effects and is used as an antidote.

History: Dabigatan was developed by Boehringer Ingelheim and was approved by the U.S. Food and Drug Administration in 2010 for reducing stroke risk in nonvalvular atrial fibrillation, with worldwide adoption under various brand names, most notably Pradaxa.