Makindo Medical Notes

💊 Dabigatran etexilate (Pradaxa®) is an oral direct thrombin inhibitor used for prevention and treatment of thromboembolic events. It offers a fixed-dose, no-INR-monitoring alternative to warfarin for non-valvular atrial fibrillation (AF) and venous thromboembolism (VTE). ⚠️ Important: Once a bottle is opened, capsules should be used within 30 days (or 120 days depending on packaging). An antidote — idarucizumab (Praxbind®) — is available for life-threatening bleeding or emergency surgery.

📘 About

• Always check the BNF entry for up-to-date dosing, renal thresholds, and interactions.
• Licensed for stroke prevention in non-valvular AF and for DVT/PE treatment or prophylaxis after initial parenteral anticoagulation.
• Roughly £3 per day — more expensive than warfarin but avoids INR monitoring, improving adherence and access for some patients.
• Eliminated mainly via the kidneys (~80% renal excretion).

⚙️ Mode of Action

• Dabigatran is a direct, competitive inhibitor of thrombin (Factor IIa).
• Thrombin is essential for conversion of fibrinogen → fibrin and for platelet activation — inhibition prevents clot formation and stabilisation.
• Half-life: 12–17 hours (prolonged in renal impairment).
• Antidote: Idarucizumab (Praxbind®) binds dabigatran with high affinity, neutralising its anticoagulant effect within minutes.

💊 Indications & Dosing (Non-Valvular Atrial Fibrillation)

• Use when ≥1 stroke risk factor present:
  • Previous stroke/TIA/systemic embolism
  • Left ventricular ejection fraction < 40%
  • NYHA class II–IV heart failure
  • Age ≥75 years, or 65–74 with diabetes, hypertension, or coronary disease
• Adults 18–74 years: 150 mg twice daily
• Adults 75–79 years: 110–150 mg twice daily (dose depends on bleeding risk)
• Adults ≥80 years: 110 mg twice daily

💉 DVT/PE Treatment and Prevention

• Start after ≥5 days of parenteral anticoagulation (e.g. LMWH).
• Adults 18–74 years: 150 mg twice daily
• Adults 75–79 years: 110–150 mg twice daily
• Adults ≥80 years: 110 mg twice daily

🔄 Interactions

• Verapamil increases dabigatran levels — use 110 mg BD.
• Also affected by amiodarone, quinidine, clarithromycin (P-gp inhibitors) — may increase drug exposure.
• Avoid concurrent anticoagulants, antiplatelets, NSAIDs unless specifically indicated — ↑ bleeding risk.

⚠️ Cautions

• Renal impairment: dose adjustment or avoidance if eGFR < 30 mL/min.
• Other bleeding risks: uncontrolled hypertension, recent surgery, peptic ulcer disease, coagulopathy.
• High HAS-BLED score → review anticoagulation risk–benefit balance.
• Bleeding can be severe; always know last dose time and renal function when managing haemorrhage.

🚫 Contraindications

• Active pathological bleeding or known bleeding disorder.
• Severe renal impairment (eGFR < 30 mL/min).
• Recent intracranial haemorrhage, major surgery, or trauma.
• GI ulceration, oesophageal varices, vascular aneurysm, or neoplasm with bleeding risk.
• Concomitant treatment with other anticoagulants (except during transition therapy).

💥 Adverse Effects

• 🔴 Bleeding: overall risk similar to warfarin; 150 mg BD associated with higher GI bleeding but lower intracranial haemorrhage.
• 💧 Dyspepsia and reflux due to acidic capsule core — may reduce adherence.
• 🧠 Haemorrhagic stroke risk lower than with warfarin.
• Rare: hypersensitivity, elevated liver enzymes.

💊 Administration & Storage

• Swallow capsules whole — do not break, chew, or crush.
• Store in the original moisture-proof container (do not transfer to dosette boxes).
• Use within 30 days (some products 120 days) of opening the bottle.

🩸 Management of Bleeding

• Assess timing of last dose and renal function (half-life ~15 hours).
• Apply local pressure and supportive measures.
• Idarucizumab (Praxbind®) 5 g IV reverses anticoagulant effect within minutes.
• Haemodialysis may remove drug if antidote unavailable.
• Discuss major bleeds with haematology — PCC or FFP may be considered.

🧠 Teaching Note

Dabigatran is the prototype direct oral anticoagulant (DOAC) targeting thrombin (Factor IIa). Compared with warfarin, it offers predictable pharmacokinetics and fewer interactions, but greater reliance on renal clearance. Always assess renal function before prescribing and periodically during therapy, especially in older or frail patients.

📚 References

• BNF: Dabigatran Etexilate
• NICE NG196: Atrial Fibrillation (2024 update)
• RE-LY Trial — Connolly SJ et al, N Engl J Med 2009
• EHRA Practical Guide on DOACs (2023)