Indications: a direct thrombin inhibitor, is given orally for prophylaxis of venous thromboembolism in adults after total hip replacement or total knee replacement surgery, Dabigatran etexilate is also licensed for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and with one or more risk factors such as previous stroke or transient ischaemic attack, symptomatic heart failure, age ≥ 75 years, diabetes mellitus, or hypertension. Dabigatran etexilate has a rapid onset of action and does not require routine anticoagulant monitoring (INR tests are unreliable in patients taking dabigatran etexilate). The most common side-effect is haemorrhage and patients should be monitored for signs of bleeding or anaemia; treatment should be stopped if severe bleeding occurs.

Cautions: also elderly; body-weight less than 50 kg; anaesthesia with postoperative indwelling epidural catheter (risk of paralysis—give initial dose at least 2 hours after catheter removal and monitor neurological signs); bacterial endocarditis; bleeding disorders; thrombocytopenia; recent biopsy or major trauma; oesophagitis, gastritis, gastro-oesophageal reflux; assess renal function (manufacturer recommends Cockroft and Gault formula to calculate creatinine clearance) before treatment in all patients and at least annually in elderly and patients with renal impairment; concomitant use of drugs that increase risk of bleeding.

Contra-indications: active bleeding; significant risk of major bleeding (e.g. recent gastro-intestinal ulcer, oesophageal varices, recent brain, spine, or ophthalmic surgery, recent intracranial haemorrhage, malignant neoplasms, vascular aneurysm); do not use as anticoagulant for prosthetic heart valve

Hepatic impairment: avoid in severe liver disease, especially if prothrombin time already prolonged Renal impairment: for prophylaxis of venous thromboembolism following knee or hip replacement surgery, reduce initial dose to 75 mg and subsequent

doses to 150 mg once daily if creatinine clearance 30–50 ml/minute; reduce dose to 75 mg once daily if creatinine clearance 30–50 ml/minute and patient receiving concomitant treatment with verapamil; avoid if creatinine clearance less than 30 ml/minute; for prophylaxis of stroke and systemic embolism in atrial fibrillation, avoid if creatinine clearance less than 30 ml/minute; monitor renal function at least annually (manufacturer recommends Cockroft and Gault formula to calculate creatinine clearance)

Pregnancy: manufacturer advises avoid unless essential—toxicity in animal studies.

Breast feeding: manufacturer advises avoid—no information available.

Side Effects: nausea, dyspepsia, diarrhoea, abdominal pain, anaemia, haemorrhage, less commonly hepatobiliary disorders, vomiting, dysphagia, gastro- intestinal ulcer, gastro-oesophageal reflux, oesophagitis, thrombocytopenia.

Dose: Prophylaxis of venous thromboembolism following total knee replacement surgery, ADULT over 18 years, 110 mg (ELDERLY over 75 years, 75 mg) 1–4 hours after surgery, followed 12–24 hours later by 220 mg (ELDERLY over 75 years or patient receiving concomitant treatment with amiodarone or verapamil, 150 mg) once daily for 9 days.

Prophylaxis of venous thromboembolism following total hip replacement surgery, ADULT over 18 years, 110 mg (ELDERLY over 75 years, 75 mg) 1–4 hours after surgery, followed 12–24 hours later by 220 mg (ELDERLY over 75 years or patient receiving concomitant treatment with amiodarone or verapamil, 150 mg) once daily for 27–34 days.

Prophylaxis of stroke and systemic embolism in non- valvular atrial fibrillation ADULT over 18 years, 150 mg (ELDERLY over 80 years, patients at high risk of bleeding, or receiving concomitant treatment with verapamil, 110 mg) twice daily