What is Pradaxa (dabigatran)?

What is Pradaxa (Dabigatran)?

Pradaxa (dabigatran etexilate) is an oral direct thrombin inhibitor anticoagulant approved by the FDA for reducing stroke risk in patients with non-valvular atrial fibrillation, treating venous thromboembolism, and preventing VTE recurrence. 1

Mechanism of Action

• Dabigatran etexilate is a prodrug that rapidly converts to dabigatran, which directly and reversibly inhibits thrombin (factor IIa) in the coagulation cascade. 2
• The conversion occurs through esterase-catalyzed hydrolysis and is independent of cytochrome P-450 enzymes, resulting in fewer drug-drug and drug-diet interactions compared to warfarin. 3
• Dabigatran is predominantly excreted renally (80% unchanged in urine) with a half-life of 12-17 hours. 2, 1

FDA-Approved Indications

The medication has three primary indications: 1

• Reduction of stroke and systemic embolism risk in adult patients with non-valvular atrial fibrillation
• Treatment of deep venous thrombosis and pulmonary embolism in adults (after 5-10 days of parenteral anticoagulation)
• Reduction of recurrent DVT/PE risk in previously treated adult patients

Dosing Regimens

For Atrial Fibrillation:

• Standard dose: 150 mg twice daily 3
• Reduced dose: 110 mg twice daily for patients ≥80 years old or taking verapamil 3
• Severe renal impairment (CrCl 15-30 mL/min): 75 mg twice daily may be considered, though safety/effectiveness not fully established 3

Critical Contraindications and Precautions

Dabigatran should NOT be used in: 3

• Patients with prosthetic heart valves or hemodynamically significant valvular disease
• Severe renal failure (creatinine clearance <15 mL/min)
• Advanced liver disease with impaired baseline clotting function
• Patients on dialysis or with end-stage chronic kidney disease 3

Renal Function Considerations

Renal impairment significantly affects dabigatran exposure: 1

• Mild impairment (CrCl 50-80 mL/min): 1.5x increase in AUC, half-life 15 hours
• Moderate impairment (CrCl 30-50 mL/min): 3.2x increase in AUC, half-life 18 hours
• Severe impairment (CrCl 15-30 mL/min): 6.3x increase in AUC, half-life 27 hours

Key Advantages Over Warfarin

Dabigatran offers several practical benefits: 2, 4

• No routine INR monitoring required
• Predictable pharmacokinetics and pharmacodynamics
• Fixed dosing regimen without need for adjustment
• 74% lower risk of hemorrhagic stroke compared to warfarin 2
• Lower rates of intracranial hemorrhage 4
• Currently the only NOAC with a specific reversal agent available 4

Important Drug Interactions

P-glycoprotein inhibitors significantly increase dabigatran levels and require caution: 2, 1

• Verapamil
• Amiodarone
• Quinidine

P-glycoprotein inducers dramatically reduce dabigatran effectiveness: 5

• Phenytoin causes undetectable dabigatran levels and should be avoided; only warfarin should be used in patients requiring phenytoin 5
• Rifampicin reduces dabigatran exposure 1

Clinical Evidence

The RE-LY trial (18,113 patients with non-valvular AF) demonstrated: 3, 2

• Dabigatran 150 mg twice daily was superior to warfarin for preventing stroke/systemic embolism (1.11% vs 1.71% per year; RR 0.65; 95% CI 0.52-0.81)
• Dabigatran 110 mg twice daily was non-inferior to warfarin (1.54% vs 1.71% per year)
• Both doses showed 74% lower hemorrhagic stroke risk versus warfarin
• Major bleeding was significantly decreased with 110 mg dose but similar with 150 mg dose compared to warfarin

Perioperative Management

For elective surgeries with high hemorrhagic risk: 3

• Stop dabigatran 4 days before surgery if CrCl >50 mL/min
• Stop dabigatran 5 days before surgery if CrCl 30-50 mL/min
• No preoperative heparin bridging needed except in very high thrombotic risk cases 3
• Neuraxial anesthesia/spinal puncture should NOT be performed with possible dabigatran concentrations present, especially in patients >80 years or with renal failure 3

Critical Clinical Pitfalls

Common issues to avoid: 2, 6

• Patients with excellent INR control on warfarin may have little benefit from switching to dabigatran 2
• Short half-life means missed doses create thromboembolism risk; compliance with twice-daily dosing is essential 3
• No established antidote for immediate reversal in hemorrhage (though specific reversal agent now exists), but dialysis can increase elimination in life-threatening bleeding 6
• Standard coagulation tests (PT, INR, aPTT) are not reliable indicators of dabigatran's anticoagulant activity 7