2 The technology
2.1 Dabigatran etexilate (Pradaxa, Boehringer Ingelheim) is a direct inhibitor of the enzyme thrombin. Thrombin is a key enzyme in blood clot (thrombus) formation because it enables the conversion of fibrinogen to fibrin during the coagulation cascade. Inhibition of thrombin prevents further development of clot formation. Clot formation may be associated with inactivity and some surgical procedures. Dabigatran etexilate holds a marketing authorisation for the primary prevention of venous thromboembolic events in adult patients who have undergone elective total hip replacement surgery or elective total knee replacement surgery. Dabigatran is taken orally.
2.2 The summary of product characteristics (SPC) states that dabigatran etexilate treatment should be started within 1–4 hours of surgery with a half dose of 110 mg. Thereafter, treatment is continued with a standard dose of 220 mg once daily for 10 days after knee replacement and for 28–35 days after hip replacement. The SPC states that for special patient populations (including people with moderate renal impairment, those over 75 years and people receiving amiodarone), a reduced dose of 150 mg (75 mg starting dose, 150 mg continuing dose) once daily is recommended.
2.3 According to data reported in the SPC, around one in seven people undergoing hip or knee surgery and treated with dabigatran etexilate experienced a bleeding event (13.8% of those receiving daily doses of 220 mg or 150 mg). Major bleeds were common and were experienced by 1.8% and 1.3% of people treated with 220 mg or 150 mg dabigatran etexilate, respectively. Other common adverse effects (those occurring in at least 1%, but less than 10% of patients) include gastrointestinal haemorrhage, wound secretion, anaemia and haematoma. For full details of side effects and contraindications, see the SPC.
2.4 Dabigatran etexilate costs £21.00 for a pack of ten 75-mg or 110-mg capsules (£126.00 for 60 capsules), excluding VAT (NHS list price as reported by the manufacturer). The cost of treatment is estimated to be £39.90 (based on the use of 19 capsules) for knee replacement and to range from £115.50 to £144.90 for hip replacement (based on the use of 55–69 capsules, respectively). Costs may vary in different settings because of negotiated procurement discounts.