Pradaxa® (dabigatran etexilate mesylate) capsules is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.
In non-valvular atrial fibrillation (NVAF)
PRADAXA 150 mg capsules
Reduces the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation *2
35% Significant risk reduction
of stroke vs warfarin2
Effects of PRADAXA compared to warfarin were more apparent in patients with lower levels of international normalized ratio (INR) control.
Lower total bleeds with
PRADAXA vs warfarin
Higher rate of total
gastrointestinal (GI) bleeds
[6.1% vs 4.0%] and major GI
bleeds [1.6% vs 1.1%]
vs warfarin
Indications and Usage
Pradaxa® (dabigatran etexilate mesylate) capsules is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.
IMPORTANT SAFETY INFORMATION ABOUT PRADAXA
CONTRAINDICATIONS
PRADAXA is contraindicated in patients with active pathological bleeding and patients with a known serious hypersensitivity reaction (e.g., anaphylactic reaction or anaphylactic shock) to PRADAXA.
WARNINGS & PRECAUTIONS: Risk of Bleeding
- PRADAXA increases the risk of bleeding and can cause significant and, sometimes, fatal bleeding. Promptly evaluate any signs or symptoms of blood loss, such as a drop in hemoglobin and/or hematocrit or hypotension. Discontinue PRADAXA in patients with active pathological bleeding
- Risk factors for bleeding include medications that increase the risk of bleeding (e.g., anti-platelet agents, heparin, fibrinolytic therapy, and chronic use of NSAIDs). PRADAXA’s anticoagulant activity and half-life are increased in patients with renal impairment
- A specific reversal agent for dabigatran is not available. Dabigatran can be dialyzed (removal of about 60% of drug over 2-3 hours) but data supporting this is limited. Activated prothrombin complex concentrates, recombinant Factor VIIa, or concentrates of factors II, IX or X may be considered but their use has not been evaluated. Protamine sulfate and vitamin K are not expected to affect dabigatran anticoagulant activity. Consider administration of platelet concentrates where thrombocytopenia is present or long-acting antiplatelet drugs have been used
WARNINGS & PRECAUTIONS: Temporary Discontinuation of PRADAXA
Discontinuing PRADAXA for active bleeding, elective surgery, or invasive procedures places patients at an increased risk of stroke. Minimize lapses in therapy.
WARNINGS & PRECAUTIONS: Effect of P-gp Inducers & Inhibitors on Dabigatran Exposure
The concomitant use of PRADAXA with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided. P-gp inhibition and impaired renal function are major independent factors in increased exposure to dabigatran. Concomitant use of P-gp inhibitors in patients with renal impairment is expected to increase exposure of dabigatran compared to either factor alone.
- For patients with moderate renal impairment (CrCl 30-50 mL/min), consider reducing the dose of PRADAXA to 75 mg twice daily when dronedarone or systemic ketoconazole is coadministered with PRADAXA
- For patients with severe renal impairment (CrCl 15-30 mL/min), avoid concomitant use of PRADAXA and P-gp inhibitors
ADVERSE REACTIONS
In the pivotal trial comparing PRADAXA to warfarin, the most frequent adverse reactions leading to discontinuation of PRADAXA were bleeding and gastrointestinal (GI) events. PRADAXA 150 mg resulted in a higher rate of major GI bleeds and any GI bleeds compared to warfarin. In patients ≥75 years of age, the risk of major bleeding may be greater with PRADAXA than with warfarin. Patients on PRADAXA 150 mg had an increased incidence of GI adverse reactions. These were commonly dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort) and gastritis-like symptoms (including GERD, esophagitis, erosive gastritis, gastric hemorrhage, hemorrhagic gastritis, hemorrhagic erosive gastritis, and GI ulcer). Drug hypersensitivity reactions were reported in <0.1% of patients receiving PRADAXA.
Other Measures Evaluated
The risk of myocardial infarction was numerically greater in patients who received PRADAXA 150 mg than in those who received warfarin.
Please click here to read the full Prescribing Information and Medication Guide for PRADAXA.
This information is intended for the U.S. only.
*Randomized Evaluation of Long-term anticoagulant therapY (RE-LY®) was a multi-center, multinational, randomized parallel group trial comparing two blinded doses of PRADAXA (110 mg twice daily and 150 mg twice daily) with open-label warfarin (dosed to target INR of 2 to 3) in 18,113 patients with non-valvular atrial fibrillation. Patients had one or more of the following additional risk factors: Previous stroke, transient ischemic attack (TIA), or systemic embolism; Left ventricular ejection fraction <40%; Symptomatic heart failure, ≥NYHA Class 2; Age ≥75 years; and Age ≥65 years and one of the following: diabetes mellitus, coronary artery disease (CAD), or hypertension. Reasons for exclusion were presence of severe heart-valve disorder, stroke within 14 days or severe stroke within 6 months before screening, hemorrhage risk-increasing conditions, CrCl <30 mL/min, active liver disease, and pregnancy. The primary objective of RE-LY was to determine non-inferiority of PRADAXA to warfarin in reducing the occurrence of the composite endpoint, stroke (ischemic and hemorrhagic) and systemic embolism. The patient's mean age was 71.5 years and the mean CHADS2 score was 2.1. Twenty percent of patients had a history of a stroke or TIA and 50% were Vitamin K antagonist (VKA) naive, defined as <2 months total lifetime exposure to a VKA. 32% of the population had never been exposed to a naïve . Concomitant diseases of patients included hypertension 79%, diabetes 23% and CAD 28%. At baseline, 40% of patients were on aspirin and 6% were on clopidogrel. For warfarin patients, the mean percentage of time in therapeutic range was 64%; the mean percentages of time INR measurements were greater than 4 (2%) or less than 1.5 (5%).
†Major bleeds fulfilled 1 or more of the following criteria: bleeding associated with a reduction in hemoglobin of at least 2 grams per deciliter or leading to a transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ (intraocular, intracranial, intraspinal, or intramuscular with compartment syndrome, retroperitoneal bleeding, intra-articular bleeding, or pericardial bleeding).
‡Patients contributed multiple events and were counted in multiple categories.
REFERENCES:
- Wann LS, Curtis AB, Ellenbogen KA, et al; writing on behalf of the 2006 ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation Writing Committee. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on dabigatran): A report of the American College of Cardiology Foundation /American Heart Association task Force on Practice Guidelines. J Am Coll Cardiol. 2011; 57:1330-1337.
- Pradaxa [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; January 2012.
PRADAXA® is a registered trademark of Boehringer Ingelheim Pharma GmbH and Co. KG and used under license.
RE-LY® is a registered service mark of Boehringer Ingelheim International GmbH and used under license.
Copyright © 2012 Boehringer Ingelheim Pharmaceuticals, Inc. All rights reserved.
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01/2012 PX176804PROF
Pradaxa Important Safety Information
Indications and Usage
Pradaxa® (dabigatran etexilate mesylate) capsules is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.
IMPORTANT SAFETY INFORMATION ABOUT PRADAXA
CONTRAINDICATIONS
PRADAXA is contraindicated in patients with active pathological bleeding and patients with a known serious hypersensitivity reaction (e.g., anaphylactic reaction or anaphylactic shock) to PRADAXA.
WARNINGS & PRECAUTIONS: Risk of Bleeding
- PRADAXA increases the risk of bleeding and can cause significant and, sometimes, fatal bleeding. Promptly evaluate any signs or symptoms of blood loss, such as a drop in hemoglobin and/or hematocrit or hypotension. Discontinue PRADAXA in patients with active pathological bleeding
- Risk factors for bleeding include medications that increase the risk of bleeding (e.g., anti-platelet agents, heparin, fibrinolytic therapy, and chronic use of NSAIDs). PRADAXA’s anticoagulant activity and half-life are increased in patients with renal impairment
- A specific reversal agent for dabigatran is not available. Dabigatran can be dialyzed (removal of about 60% of drug over 2-3 hours) but data supporting this is limited. Activated prothrombin complex concentrates, recombinant Factor VIIa, or concentrates of factors II, IX or X may be considered but their use has not been evaluated. Protamine sulfate and vitamin K are not expected to affect dabigatran anticoagulant activity. Consider administration of platelet concentrates where thrombocytopenia is present or long-acting antiplatelet drugs have been used
WARNINGS & PRECAUTIONS: Temporary Discontinuation of PRADAXA
Discontinuing PRADAXA for active bleeding, elective surgery, or invasive procedures places patients at an increased risk of stroke. Minimize lapses in therapy.
WARNINGS & PRECAUTIONS: Effect of P-gp Inducers & Inhibitors on Dabigatran Exposure
The concomitant use of PRADAXA with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided. P-gp inhibition and impaired renal function are major independent factors in increased exposure to dabigatran. Concomitant use of P-gp inhibitors in patients with renal impairment is expected to increase exposure of dabigatran compared to either factor alone.
- For patients with moderate renal impairment (CrCl 30-50 mL/min), consider reducing the dose of PRADAXA to 75 mg twice daily when dronedarone or systemic ketoconazole is coadministered with PRADAXA
- For patients with severe renal impairment (CrCl 15-30 mL/min), avoid concomitant use of PRADAXA and P-gp inhibitors
ADVERSE REACTIONS
In the pivotal trial comparing PRADAXA to warfarin, the most frequent adverse reactions leading to discontinuation of PRADAXA were bleeding and gastrointestinal (GI) events. PRADAXA 150 mg resulted in a higher rate of major GI bleeds and any GI bleeds compared to warfarin. In patients ≥75 years of age, the risk of major bleeding may be greater with PRADAXA than with warfarin. Patients on PRADAXA 150 mg had an increased incidence of GI adverse reactions. These were commonly dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort) and gastritis-like symptoms (including GERD, esophagitis, erosive gastritis, gastric hemorrhage, hemorrhagic gastritis, hemorrhagic erosive gastritis, and GI ulcer). Drug hypersensitivity reactions were reported in <0.1% of patients receiving PRADAXA.
Other Measures Evaluated
The risk of myocardial infarction was numerically greater in patients who received PRADAXA 150 mg than in those who received warfarin.
Please click here to read the full Prescribing Information and Medication Guide for PRADAXA.
This information is intended for the U.S. only.
