| Initial U.S. Approval: 2010
The chemical name for dabigatran etexilate mesylate, a direct thrombin inhibitor, is β-Alanine, N-[[2-[[[4-[[[(hexyloxy)carbonyl]amino]iminomethyl] phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl-,ethyl ester, methanesulfonate.
Dabigatran etexilate mesylate is a yellow-white to yellow powder. A saturated solution in pure water has a solubility of 1.8 mg/mL. It is freely soluble in methanol, slightly soluble in ethanol, and sparingly soluble in isopropanol.
The 150 mg capsule for oral administration contains 172.95 mg dabigatran etexilate mesylate, which is equivalent to 150 mg of dabigatran etexilate, and the following inactive ingredients: acacia, dimethicone, hypromellose, hydroxypropyl cellulose, talc, and tartaric acid. The capsule shell is composed of carrageenan, FD&C Blue No. 2 (150 mg only), FD&C Yellow No. 6, hypromellose, potassium chloride, titanium dioxide, and black edible ink. The 75 mg capsule contains 86.48 mg dabigatran etexilate mesylate, equivalent to 75 mg dabigatran etexilate, and is otherwise similar to the 150 mg capsule.
| CLINICAL PHARMACOLOGY
Mechanism of Action
Dabigatran and its acyl glucuronides are competitive, direct thrombin inhibitors. Because thrombin (serine protease) enables the conversion of fibrinogen into fibrin during the coagulation cascade, its inhibition prevents the development of a thrombus. Both free and clot-bound thrombin, and thrombin-induced platelet aggregation are inhibited by the active moieties
| INDICATIONS AND USAGE
PRADAXA is a direct thrombin inhibitor indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation
| Active pathological bleeding.
History of serious hypersensitivity reaction to PRADAXA.
| WARNINGS AND PRECAUTIONS
Risk of bleeding: PRADAXA can cause serious and, sometimes, fatal bleeding. Promptly evaluate signs and symptoms of blood loss.
Temporary discontinuation: Avoid lapses in therapy to minimize risk of stroke.
P-gp inducers and inhibitors: Effects on dabigatran exposure
P-gp inhibitors dronedarone and systemic ketoconazole in patients with moderate renal impairment (CrCl 30-50 mL/min): Consider reducing PRADAXA dose to 75 mg twice daily.
P-gp inhibitors in patients with severe renal impairment (CrCl <30 mL/min): PRADAXA use not recommended.
USE IN SPECIFIC POPULATIONS
| Most common adverse reactions (>15%) are gastritis-like symptoms and bleeding.
To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at (800) 542-6257 or (800) 459-9906 TTY or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
| DOSAGE AND ADMINISTRATION
For patients with creatinine clearance (CrCl) >30 mL/min, the recommended dose of PRADAXA is 150 mg taken orally, twice daily, with or without food. For patients with severe renal impairment (CrCl 15-30 mL/min), the recommended dose of PRADAXA is 75 mg twice daily. Dosing recommendations for patients with a CrCl <15 mL/min or on dialysis cannot be provided.
In patients with moderate renal impairment (CrCl 30-50 mL/min), concomitant use of the P-gp inhibitor dronedarone or systemic ketoconazole can be expected to produce dabigatran exposure similar to that observed in severe renal impairment. Consider reducing the dose of PRADAXA to 75 mg twice daily.
Renal function should be assessed by calculating the CrCl prior to initiation of treatment with PRADAXA. While on treatment, renal function should be assessed in clinical situations which may be associated with a decline in renal function. In patients with CrCl <50 mL/min or >75 years of age, renal function should be assessed at least once a year.
Instruct patients to swallow the capsules whole. Breaking, chewing, or emptying the contents of the capsule can result in increased exposure.
If a dose of PRADAXA is not taken at the scheduled time, the dose should be taken as soon as possible on the same day; the missed dose should be skipped if it cannot be taken at least 6 hours before the next scheduled dose. The dose of PRADAXA should not be doubled to make up for a missed dose.
Converting from or to Warfarin
When converting from PRADAXA to warfarin, adjust the starting time of warfarin based on creatinine clearance as follows:
For CrCl ≥50 mL/min, start warfarin 3 days before discontinuing PRADAXA.
Converting from or to Parenteral Anticoagulants
For patients currently taking PRADAXA, wait 12 hours (CrCl ≥30 mL/min) or 24 hours (CrCl <30 mL/min) after the last dose of PRADAXA before initiating treatment with a parenteral anticoagulant.
Surgery and Interventions
If surgery cannot be delayed, there is an increased risk of bleeding. This risk of bleeding should be weighed against the urgency of intervention. Bleeding risk can be assessed by the ecarin clotting time (ECT). This test is a better marker of the anticoagulant activity of dabigatran than activated partial thromboplastin time (aPTT) or thrombin time (TT). If ECT is not available, the aPTT test provides an approximation of PRADAXA’s anticoagulant activity. INR tests are unreliable in patients on PRADAXA.
| DOSAGE FORMS AND STRENGTHS
Capsules: 75 mg and 150 mg
HOW SUPPLIED/STORAGE AND HANDLING
NDC 0597-0149-54 Unit of use bottle of 60 capsules
PRADAXA 150 mg capsules have a light blue opaque cap imprinted with the Boehringer Ingelheim company symbol and a cream-colored opaque body imprinted with “R150”. The color of the imprinting is black. The capsules are supplied in the packages listed:
NDC 0597-0135-54 Unit of use bottle of 60 capsules
Keep out of the reach of children.
| Package Insert data:
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA
Revised: November 2011
The brands listed above are trademarks of their respective owners and are not trademarks of Boehringer Ingelheim Pharmaceuticals, Inc. The owners of these brands are not affiliated with and do not endorse Boehringer Ingelheim Pharmaceuticals, Inc., or its products.
Copyright 2011 Boehringer Ingelheim Pharmaceuticals, Inc.
National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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