Dabigatran


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Prophylaxis of postoperative venous thromboembolism Initial: 110 mg given within 1-4 hours after surgery, followed by 220 mg once daily for 10 days (knee replacement); 28-35 days (hip replacement).  Prophylaxis of stroke and systemic embolism in non-valvular atrial fibrillation 150 mg bid. Deep vein thrombosis; Pulmonary embolism Treatment, and prophylaxis of recurrent cases following initial therapy with parenteral anticoagulant for at least 5 days: 150 mg bid. Duration of treatment is individualised based on assessment of treatment benefit against the risk of bleeding. Dose discontinuation may be required when switching to and from dabigatran or based on patient safety and tolerability (refer to detailed product guideline).
Dosage Details
Oral
Prophylaxis of postoperative venous thromboembolism
Adult: Initially, 110 mg given within 1-4 hours after surgery, followed by 220 mg once daily for 10 days (knee replacement); 28-35 days (hip replacement). Dose discontinuation may be required when switching to and from dabigatran or based on patient safety and tolerability (refer to detailed product guideline).
Elderly: ≥75 years Initially, 75 mg given within 1-4 hours after surgery, followed by 150 mg once daily for 10 days (knee replacement); 28-35 days (hip replacement).

Oral
Prophylaxis of stroke and systemic embolism in non-valvular atrial fibrillation
Adult: 150 mg bid. Dose discontinuation may be required when switching to and from dabigatran or based on patient safety and tolerability (refer to detailed product guideline).
Elderly: 75-80 years 150 mg or 110 mg bid, based on individual assessment of the risks of thromboembolism and bleeding; ≥80 years 110 mg bid.

Oral
Deep vein thrombosis, Pulmonary embolism
Adult: Treatment and prophylaxis of recurrent cases following initial therapy with parenteral anticoagulant for at least 5 days: 150 mg bid. Duration of treatment is individualised based on assessment of treatment benefit against the risk of bleeding. Dose discontinuation may be required when switching to and from dabigatran or based on patient safety and tolerability (refer to detailed product guideline).
Elderly: 75-80 years 150 mg or 110 mg bid, based on individual assessment of the risks of thromboembolism and bleeding; ≥80 years 110 mg bid.
Special Patient Group
Postoperative venous thromboembolism prophylaxis

Patients taking concomitant amiodarone, or quinidine: Initially, 75 mg given within 1-4 hours after surgery, followed by 150 mg once daily for 10 days (knee replacement); 28-35 days (hip replacement).
Patients taking concomitant verapamil with moderate renal impairment (CrCl 30-50 mL/min): Reduce dose for up to 75 mg daily.

Treatment and prevention of deep vein thrombosis, and pulmonary embolism; Prophylaxis of stroke and systemic embolism in non-valvular atrial fibrillation

Patients taking concomitant verapamil: 110 mg bid.
Patients with gastritis, oesophagitis, gastro-oesophageal reflux, or at increased risk of bleeding: 150 mg or 110 mg bid based on individual assessment of the risks of thromboembolism and bleeding.
Renal Impairment
Prophylaxis of postoperative venous thromboembolism:
CrCl (mL/min) Dosage
<30 Contraindicated.
30-50 Initially, 75 mg given within 1-4 hours after surgery, followed by 150 mg once daily for 10 days (knee replacement); 28-35 days (hip replacement). 

Prophylaxis of stroke and systemic embolism in non-valvular atrial fibrillation; Deep vein thrombosis; Pulmonary embolism:
CrCl (mL/min) Dosage
<30 Contraindicated.
30-50 150 mg bid, or 110 mg bid, based on individual assessment of the risks of thromboembolism and bleeding.
Administration
May be taken with or without food. Swallow whole, do not chew/crush.
Contraindications
Active pathological bleeding; bleeding diathesis; conditions or lesions at risk of clinically significant bleeding (e.g. current or recent gastrointestinal ulceration, malignant neoplasms at high risk of bleeding; recent brain, spinal, ophthalmic injury and/or surgery; recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms, major intraspinal or intracerebral vascular abnormalities); haemostatic impairment. Concomitant use with parenteral anticoagulants except when given to maintain an open central venous or arterial catheter, or during catheter ablation; oral anticoagulants except when switching to oral anticoagulant therapy; antithrombin agents; strong P-glycoprotein inhibitors. Severe renal impairment CrCl <30 mL/min. Patient with mechanical prosthetic heart valves requiring anticoagulant treatment.
Special Precautions
Patient with increased risk of bleeding (e.g. recent biopsy, major trauma, bacterial endocarditis), history of traumatic or repeated epidural/spinal punctures, spinal deformity or surgery. Not recommended in patients with valvular heart disease including the presence of bioprosthetic heart valves; history of thrombosis diagnosed with antiphospholipid syndrome. Hepatic and moderate renal impairment. Elderly. Pregnancy and lactation. Avoid abrupt discontinuation of treatment.
Adverse Reactions
Significant: Thromboembolic events (premature discontinuation), bleeding, spinal or epidural haematoma resulting to long term or permanent paralysis.
Blood and lymphatic system disorders: Anaemia.
Gastrointestinal disorders: Dyspepsia, gastritis, nausea, diarrhoea, abdominal pain, gastrointestinal haemorrhage.
Investigations: Decreased Hb, abnormal LFT.
Nervous system disorders: Intracranial haemorrhage.
Renal and urinary disorders: Genitourological haemorrhage, haematuria.
Skin and subcutaneous tissue disorders: Skin haemorrhage.
Vascular disorders: Epistaxis.
Potentially Fatal: Severe bleeding.
MonitoringParameters
Assess renal function at least once a year during treatment. Monitor CBC, aPTT, prothrombin time, serum creatinine, and LFTs prior to treatment initiation, when clinically indicated, and at least annually thereafter. Closely observe for signs of bleeding or anaemia.
Overdosage
Symptoms: Haemorrhagic complications. Management: Symptomatic and supportive treatment. Individualised based on the severity and location of haemorrhage. May give activated charcoal if ingestion occurred within 1-2 hours of presentation; consider surgical haemostasis and blood volume replacement. Administer idarucizumab as an antidote for situations when rapid reversal of anticoagulant effect is required. May consider administration of coagulation factor concentrates (activated or non-activated) or recombinant Factor VIIa; platelet concentrates in case of thrombocytopenia or concomitant use of long-acting antiplatelet agents.
Drug Interactions
Increased plasma concentration with verapamil, amiodarone, quinidine, clarithromycin, ticagrelor, posaconazole. May increase the risk of spinal or epidural haematomas with neuraxial anaesthesia. May either increase or decrease serum concentration with ritonavir. May decrease plasma levels with pantoprazole. Decreased plasma concentrations with P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin).
Potentially Fatal: Increased risk of major bleeding with parenteral anticoagulants (e.g. unfractionated heparin, enoxaparin, dalteparin, fondaparinux, desirudin), vitamin K antagonists, oral anticoagulants (e.g. warfarin, rivaroxaban, apixaban), antiplatelets (e.g. clopidogrel, ticlopidine, prasugrel, dextran, sulfinpyrazone), aspirin, NSAIDs, SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs). Increased plasma concentrations with strong P-gp inhibitors (e.g. systemic ketoconazole, itraconazole, dronedarone, ciclosporin, tacrolimus).
Food Interaction
Decreased plasma concentration with St. John’s wort.
Action
Description: Dabigatran is a competitive, selective, reversible direct inhibitor of free and fibrin-bound thrombin. It also prevents thrombin-mediated effects including cleavage of fibrinogen to fibrin monomers, activation of factors V, VIII, XI, and XIII, and inhibition of thrombin-induced platelet aggregation.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract; initially slow (postoperative). Food delays time to peak plasma concentration. Bioavailability: Approx 3-7%, may be increased by up to 75% (without cap shell). Time to peak plasma concentration: 0.5-2 hours; approx 6 hours (postoperative).
Distribution: Enters breast milk. Volume of distribution: 50-70 L. Plasma protein binding: Approx 35%.
Metabolism: Dabigatran etexilate is rapidly and completely metabolised in the liver by plasma and hepatic esterases via hydrolysis to its active metabolite, dabigatran, which then undergoes hepatic glucuronidation to form its active acylglucuronide isomers.
Excretion: Mainly via urine (approx 80-85%, as unchanged drug). Elimination half-life: Approx 12-17 hours.
Chemical Structure

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Dabigatran, CID=216210, https://pubchem.ncbi.nlm.nih.gov/compound/Dabigatran (accessed on Jan. 20, 2020)

Storage
Store at 25°C. Protect from moisture.
ATC Classification
B01AE07 - dabigatran etexilate ; Belongs to the class of direct thrombin inhibitors. Used in the treatment of thrombosis.
References
Anon. Dabigatran Etexilate Mesylate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 17/07/2019.

Anon. Dabigatran Etexilate. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 17/07/2019.

Buckingham R (ed). Dabigatran. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 17/07/2019.

Joint Formulary Committee. Dabigatran Etexilate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 17/07/2019.

Pradaxa Capsule (Boehringer Ingelheim Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 17/07/2019.

Disclaimer: This information is independently developed by MIMS based on Dabigatran from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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