Dabigatran Dosage, Side Effects

Dabigatran dosage , side effects:

Dabigatran (Pradaxa, Prazaxa, others) is a direct thrombin inhibitor used as an anticoagulant to prevent and treat blood clots. Here’s a detailed overview:

Brand Names:

• Pradaxa (most common)
• Prazaxa (Japan)
• Generic versions available in some countries.

Approved Uses:

1. Prevention of stroke & systemic embolism in non-valvular atrial fibrillation (NVAF).
2. Treatment & prevention of deep vein thrombosis (DVT) & pulmonary embolism (PE).
3. Post-surgical prophylaxis (e.g., after hip or knee replacement in some regions).

Dosage:

• Atrial Fibrillation (Stroke Prevention):
  • 150 mg twice daily (standard).
  • 110 mg twice daily (if high bleeding risk, elderly, or moderate renal impairment).
• DVT/PE Treatment:
  • 150 mg twice daily after initial parenteral anticoagulation (e.g., heparin).
• Post-Surgical Prophylaxis:
  • 220 mg once daily (110 mg first dose 1–4 hours post-surgery, then 220 mg daily for 28–35 days).

Renal Dose Adjustments:

• CrCl >30–50 mL/min: Reduce dose (e.g., 75 mg twice daily in the U.S.).
• CrCl <30 mL/min: Avoid (limited data, increased bleeding risk).
• Dialysis: Not recommended.

Missed Dose:

• If within 6 hours of next dose, skip; otherwise, take ASAP. Do not double dose.

Mechanism of Action:

• Direct thrombin (Factor IIa) inhibitor, preventing fibrin formation and clot propagation.

Key Interactions:

1. Strong P-gp Inducers (↓ Dabigatran levels):
   • Rifampin, carbamazepine, St. John’s wort (avoid).
2. P-gp Inhibitors (↑ Dabigatran levels):
   • Ketoconazole, dronedarone, verapamil, amiodarone, clarithromycin (use with caution; dose reduction may be needed).
3. Other Anticoagulants/Antiplatelets (↑ Bleeding Risk):
   • Warfarin, heparin, aspirin, NSAIDs, SSRIs.
4. Proton Pump Inhibitors (PPIs):
   • May reduce dabigatran absorption (take PPI 2 hours apart if possible).

Side Effects:

• Common: GI upset (dyspepsia, nausea, diarrhea).
• Serious: Major bleeding (GI, intracranial), allergic reactions, dyspepsia.

Reversal Agent:

• Idarucizumab (Praxbind) – monoclonal antibody for emergency reversal.

Contraindications:

• Active bleeding, mechanical heart valves (↑ risk of thromboembolism), severe renal impairment (CrCl <30 mL/min), hypersensitivity.

Monitoring:

• No routine INR monitoring, but assess renal function (CrCl) periodically.
• aPTT or thrombin time (TT) can indicate anticoagulant effect (not standardized for dosing).

Special Considerations:

• Switching from Warfarin: Start dabigatran once INR <2.0.
• Perioperative Management: Discontinue 1–2 days before surgery (longer if high bleeding risk/CrCl <50).