Manufacturer:

Boehringer Ingelheim Pharmaceuticals

Pharmacological Class:

Direct thrombin inhibitor.

Active Ingredient(s):

Dabigatran etexilate mesylate 75mg, 150mg; caps.

Indication(s):

To reduce risk of stroke and systemic embolism in non-valvular atrial fibrillation.

Pharmacology:

By directly inhibiting thrombin, dabigatran and its active metabolites prevent the development of a thrombus. Both free and clot-bound thrombin, and thrombin-induced platelet aggregation are inhibited.

Dabigatran prolongs the aPTT, ecarin clotting time (ECT), and TT at therapeutic doses. With a dose of 150mg twice daily, the median peak aPTT is about 2x control; 12 hours after the last dose the median aPTT is 1.5x control. International normalized ratio (INR) is relatively insensitive to the activity of dabigatran. When converting a patient from dabigatran to warfarin, the INR is not likely to be useful until at least 2 days after discontinuing dabigatran.

The capsules should not be opened before administering, as this can increase the bioavailability of the drug by 75%.

Clinical Trials:

A multi-center, randomized parallel-group study compared two blinded doses of dabigatran (110mg twice daily or 150mg twice daily) with open-label warfarin (dosed to target INR of 2 to 3) in patients with non-valvular, persistent, paroxysmal, or permanent atrial fibrillation and one or more additional risk factors (previous stroke, TIA, or systemic embolism; left ventricular ejection fraction <40%; symptomatic heart failure ≥NYHA Class 2; age ≥75years; or age ≥65years with either diabetes, coronary artery disease, or hypertension). The primary objective was to determine if the study drug was non-inferior to warfarin in reducing the occurrence of a composite endpoint, stroke (ischemic and hemorrhagic) and systemic embolism. The study was designed to ensure that dabigatran preserved more than 50% of warfarin’s effect as established by previous warfarin studies in atrial fibrillation. Over 18,000 patients were randomized and followed for a median of 2 years. Compared to warfarin and dabigatran 110mg twice daily, dabigatran 150mg twice daily significantly reduced the primary composite endpoint (stroke and systemic embolism).

Legal Classification:

Rx

Adults:

Swallow whole. CrCl>30mL/min: 150mg twice daily. Renal impairment (CrCl 15–30mL/min): 75mg twice daily; CrCl<15mL/min or on dialysis: not recommended. Converting from warfarin, other anticoagulants: see literature. Take missed dose as soon as possible on same day; skip dose if it cannot be taken at least 6 hours before the next scheduled dose; do not double doses.

Children:

Not recommended.

Contraindication(s):

Active pathological bleeding.

Warnings/Precautions:

Increased risk of serious bleeding. Promptly evaluate signs/symptoms of blood loss (eg, a drop in hemoglobin and/or hematocrit or hypotension). Suspend treatment before invasive therapy or surgery, including dental procedures (see literature); restart promptly. Avoid lapses in therapy. Bleeding risk can be assessed by ecarin clotting time (ECT), or if not available, aPTT. Severe renal impairment. Elderly (>75 years). Labor & delivery. Pregnancy (Cat.C). Nursing mothers.

Interaction(s):

Antagonized by P-gp inducers (eg, rifampin); avoid. Increased dabigatran levels with P-gp inhibitors (eg, ketoconazole, amiodarone, quinidine, clopidogrel). May be potentiated by immediate-release verapamil; separate dosing by ≥1 hour. Concomitant NSAIDs, platelet inhibitors, heparin, fibrinolytic therapy: increased risk of bleeding. Switching to or from warfarin: monitor closely.

Adverse Reaction(s):

Gastritis-like symptoms (eg, GERD, esophagitis, erosive gastritis, gastric hemorrhage), bleeding (may be fatal).

How Supplied:

Caps—60

Last Updated:

11/19/2010