Drug Action
Dabigatran etexilate is a direct thrombin inhibitor with a rapid onset of action.
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Drug reference
Dabigatran etexilate is a direct thrombin inhibitor with a rapid onset of action.
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Prophylaxis of venous thromboembolism following total knee replacement surgery ▶BY MOUTH ▶Adult 18–74 years: 110 mg, to be taken 1–4 hours after surgery, followed by 220 mg once daily for 10 days, to be taken on the first day after surgery ▶Adult 75 years and over: 75 mg, to be taken 1–4 hours after surgery, followed by 150 mg once daily for 10 days, to be taken on the first day after surgery Prophylaxis of venous thromboembolism following total knee replacement surgery in patients receiving concomitant treatment with amiodarone or verapamil ▶BY MOUTH ▶Adult 18–74 years: 75 mg, to be taken 1–4 hours after surgery, followed by 150 mg once daily for 10 days, to be taken on the first day after surgery ▶Adult 75 years and over: 75 mg, to be taken 1–4 hours after surgery, followed by 150 mg once daily for 10 days, to be taken on the first day after surgery Prophylaxis of venous thromboembolism following total hip replacement surgery ▶BY MOUTH ▶Adult 18–74 years: 110 mg, to be taken 1–4 hours after surgery, followed by 220 mg once daily for 28–35 days, to be taken on the first day after surgery ▶Adult 75 years and over: 75 mg, to be taken 1–4 hours after surgery, followed by 150 mg once daily for 28–35 days, to be taken on the first day after surgery Prophylaxis of venous thromboembolism following total hip replacement surgery in patients receiving concomitant treatment with amiodarone or verapamil ▶BY MOUTH ▶Adult 18–74 years: 75 mg, to be taken 1–4 hours after surgery, followed by 150 mg once daily for 28–35 days, to be taken on the first day after surgery ▶Adult 75 years and over: 75 mg, to be taken 1–4 hours after surgery, followed by 150 mg once daily for 28–35 days, to be taken on the first day after surgery Treatment of deep-vein thrombosis | Treatment of pulmonary embolism | Prophylaxis of recurrent deep- vein thrombosis | Prophylaxis of recurrent pulmonary embolism ▶BY MOUTH ▶Adult 18–74 years: 150 mg twice daily, following at least 5 days treatment with a parenteral anticoagulant ▶Adult 75–79 years: 110–150 mg twice daily, following at least 5 days treatment with a parenteral anticoagulant ▶Adult 80 years and over: 110 mg twice daily, following at least 5 days treatment with a parenteral anticoagulant Treatment of deep-vein thrombosis in patients with moderate renal impairment | Treatment of deep-vein thrombosis in patients at increased risk of bleeding | Treatment of pulmonary embolism in patients with moderate renal impairment | Treatment of pulmonary embolism in patients at increased risk of bleeding | Prophylaxis of recurrent deep-vein thrombosis in patients with moderate renal impairment | Prophylaxis of recurrent deep-vein thrombosis in patients at increased risk of bleeding | Prophylaxis of recurrent pulmonary embolism in patients with moderate renal impairment | Prophylaxis of recurrent pulmonary embolism in patients at increased risk of bleeding ▶BY MOUTH ▶Adult: 110–150 mg twice daily, following at least 5 days treatment with a parenteral anticoagulant Treatment of deep-vein thrombosis in patients receiving concomitant treatment with verapamil | Treatment of pulmonary embolism in patients receiving concomitant treatment with verapamil | Prophylaxis of recurrent deep-vein thrombosis in patients receiving concomitant treatment with verapamil | Prophylaxis of recurrent pulmonary embolism in patients receiving concomitant treatment with verapamil ▶BY MOUTH ▶Adult: 110 mg twice daily, following at least 5 days treatment with a parenteral anticoagulant Prophylaxis of stroke and systemic embolism in 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 ▶BY MOUTH ▶Adult 18–74 years: 150 mg twice daily ▶Adult 75–79 years: 110–150 mg twice daily ▶Adult 80 years and over: 110 mg twice daily Prophylaxis of stroke and systemic embolism in 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 in patients receiving concomitant treatment with verapamil ▶BY MOUTH ▶Adult: 110 mg twice daily Prophylaxis of stroke and systemic embolism in 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, in patients at increased risk of bleeding | Prophylaxis of stroke and systemic embolism in 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, in patients with moderate renal impairment ▶BY MOUTH ▶Adult: 110–150 mg twice daily DOSE EQUIVALENCE AND CONVERSION ▶For information on changing from, or to, other anticoagulants, consult product literature.
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Active bleeding. antiphospholipid syndrome (increased risk of recurrent thrombotic events). do not use as anticoagulant for prosthetic heart valve. malignant neoplasms. oesophageal varices. recent brain surgery. recent gastro-intestinal ulcer. recent intracranial haemorrhage. recent ophthalmic surgery. recent spine surgery. significant risk of major bleeding. vascular aneurysm
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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. body-weight less than 50 kg. elderly. gastritis. gastro-oesophageal reflux. oesophagitis. recent biopsy. recent major trauma. thrombocytopenia CAUTIONS, FURTHER INFORMATION ▶Elderly For direct thrombin inhibitors, prescription potentially inappropriate (STOPP criteria): . with concurrent significant bleeding risk, such as uncontrolled severe hypertension, bleeding diathesis or recent non-trivial spontaneous bleeding (high risk of bleeding) . for first deep venous thrombosis without continuing provoking risk factors (e.g. thrombophilia) for greater than 6 months (no proven added benefit) . for first pulmonary embolus without continuing provoking risk factors for greater than 12 months (no proven added benefit) . as part of dual therapy with an antiplatelet agent in patients with stable coronary, cerebrovascular or peripheral arterial disease, without a clear indication for anticoagulant therapy (no added benefit) . if eGFR less than 30 ml/min/1.73 m2 (risk of bleeding) See also Prescribing in the elderly p. 33.
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Dabigatran etexilate, is given orally for prophylaxis of venous thromboembolism in adults after total hip replacement or total knee replacement surgery; it is also licensed for the treatment of deep-vein thrombosis and pulmonary embolism, and prophylaxis of recurrent deep-vein thrombosis and pulmonary embolism in adults. Duration of treatment should be determined by balancing the benefit of treatment with the bleeding risk; shorter duration of treatment (at least 3 months) should be based on transient risk factors i.e recent surgery, trauma, immobilisation, and longer duration of treatment should be based on permanent risk factors, or idiopathic deep- vein thrombosis or pulmonary embolism.
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NICE decisions ▶Dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults (September 2008) NICE TA157 Dabigatran etexilate (Pradaxa ®) is an option for the prophylaxis of venous thromboembolism in adults after total hip replacement or total knee replacement surgery. www.nice.org.uk/guidance/ta157 ▶Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation (March 2012) NICE TA249 Dabigatran etexilate (Pradaxa ®) is an option for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and with one or more of the following risk factors: . previous stroke, transient ischaemic attack, or systemic embolism . left ventricular ejection fraction <40% . symptomatic heart failure of New York Heart Association (NYHA) class 2 or above . age 75 years . age 65 years in patients with diabetes mellitus, coronary artery disease, or hypertension The risks and benefits of dabigatran compared to warfarin should be discussed with the patient. www.nice.org.uk/guidance/ta249 ▶Dabigatran etexilate for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism (December 2014) NICE TA327 Dabigatran etexilate (Pradaxa ®) is recommended, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults. www.nice.org.uk/guidance/ta327
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MHRA/CHM ADVICE: DIRECT-ACTING ORAL ANTICOAGULANTS (DOACS): INCREASED RISK OF RECURRENT THROMBOTIC EVENTS IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME (JUNE 2019) A clinical trial has shown an increased risk of recurrent thrombotic events associated with rivaroxaban compared with warfarin, in patients with antiphospholipid syndrome and a history of thrombosis. There may be a similar risk associated with other DOACs. Healthcare professionals are advised that DOACs are not recommended in patients with antiphospholipid syndrome, particularly high-risk patients who test positive for all three antiphospholipid tests—lupus anticoagulant, anticardiolipin antibodies, and anti-beta2 Cardiovascular system glycoprotein I antibodies. Continued treatment should be reviewed in these patients to determine if appropriate, and switching to a vitamin K antagonist such as warfarin should be considered.
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→Appendix 1: dabigatran
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▶Common or very common Hepatic function abnormal ▶Uncommon Anaemia. diarrhoea. haemorrhage. hyperbilirubinaemia. nausea. post procedural complications. vomiting. wound complications ▶Rare or very rare Angioedema. dysphagia. gastrointestinal discomfort. gastrointestinal disorders. intracranial haemorrhage. post procedural drainage. skin reactions. thrombocytopenia. wound drainage ▶Frequency not known Bronchospasm
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Manufacturer advises avoid unless essential—toxicity in animal studies.
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Manufacturer advises avoid—no information available.
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Manufacturer advises avoid in severe impairment; consider avoiding in those with liver enzymes greater than 2 times the upper limit of normal (no information available).
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Manufacturer advises avoid if creatinine clearance less than 30 mL/minute. Dose adjustments When used 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; consider reducing dose to 75 mg once daily if creatinine clearance 30–50 mL/minute and patient receiving concomitant treatment with verapamil. When used for treatment of deep-vein thrombosis and pulmonary embolism, prophylaxis of recurrent deep-vein thrombosis and pulmonary embolism, prophylaxis of stroke and systemic embolism in non-valvular atrial fibrillation, Cardiovascular system consider reduced dose of 110–150 mg twice daily if creatinine clearance 30–50 mL/minute, based on individual assessment of thromboembolic risk and risk of bleeding. Monitoring In renal impairment monitor renal function at least annually (manufacturer recommends Cockroft and Gault formula to calculate creatinine clearance).
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▶Patients should be monitored for signs of bleeding or anaemia; treatment should be stopped if severe bleeding occurs. ▶No routine anticoagulant monitoring required (INR tests are unreliable). ▶Assess renal function (manufacturer recommends Cockroft and Gault formula to calculate creatinine clearance) before treatment in all patients and at least annually in elderly.
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When given concomitantly with amiodarone or verapamil, doses should be taken at the same time.
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There can be variation in the licensing of different medicines containing the same drug. Capsule CAUTIONARY AND ADVISORY LABELS 10, 25 ▶Pradaxa (Boehringer Ingelheim Ltd) Dabigatran etexilate (as Dabigatran etexilate mesilate) 75 mg Pradaxa 75mg capsules | 10 capsule P £8.50 | 60 capsule P £51.00 DT = £51.00 Dabigatran etexilate (as Dabigatran etexilate mesilate) 110 mg Pradaxa 110mg capsules | 10 capsule P £8.50 | 60 capsule P £51.00 DT = £51.00 Dabigatran etexilate (as Dabigatran etexilate mesilate) 150 mg Pradaxa 150mg capsules | 60 capsule P £51.00 DT = £51.00 ANTITHROMBOTIC DRUGS › TISSUE PLASMINOGEN ACTIVATORS eiiii F 229
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Patients should be provided with an alert card and advised to keep it with them at all times.
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110 mg, to be taken 1–4 hours after
First-line fragment. Read the complete Indications and Dose section above.
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75 mg, to be taken 1–4 hours
First-line fragment. Read the complete Indications and Dose section above.
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75 mg, to be taken 1–4 hours after
First-line fragment. Read the complete Indications and Dose section above.
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75 mg, to be taken 1–4 hours
First-line fragment. Read the complete Indications and Dose section above.
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110 mg, to be taken 1–4 hours after
First-line fragment. Read the complete Indications and Dose section above.
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75 mg, to be taken 1–4 hours
First-line fragment. Read the complete Indications and Dose section above.
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75 mg, to be taken 1–4 hours after
First-line fragment. Read the complete Indications and Dose section above.
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75 mg, to be taken 1–4 hours
First-line fragment. Read the complete Indications and Dose section above.
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150 mg twice daily, following at least
First-line fragment. Read the complete Indications and Dose section above.
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110–150 mg twice daily, following at
First-line fragment. Read the complete Indications and Dose section above.
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110 mg twice daily, following at
First-line fragment. Read the complete Indications and Dose section above.
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110–150 mg twice daily, following at least 5 days
First-line fragment. Read the complete Indications and Dose section above.
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110 mg twice daily, following at least 5 days
First-line fragment. Read the complete Indications and Dose section above.
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150 mg twice daily
First-line fragment. Read the complete Indications and Dose section above.
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110–150 mg twice daily
First-line fragment. Read the complete Indications and Dose section above.
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110 mg twice daily
First-line fragment. Read the complete Indications and Dose section above.
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110 mg twice daily
First-line fragment. Read the complete Indications and Dose section above.
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110–150 mg twice daily
First-line fragment. Read the complete Indications and Dose section above.
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