Dabigatran etexilate oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of dabigatran etexilate (as mesilate).
Drugs List
Therapeutic Indications
Uses
Deep vein thrombosis - prophylaxis
Deep vein thrombosis - treatment
Nonvalvular atrial fibrillation; prevention of stroke and systemic embolism
Prevention of VTE in patients undergoing hip replacement surgery
Prevention of VTE in patients undergoing knee replacement surgery
Pulmonary embolism - prophylaxis
Pulmonary embolism - treatment
Primary prevention of venous thromboembolic events (VTE) in adults who have undergone elective total hip replacement surgery.
Primary prevention of venous thromboembolic events (VTE) in adults who have undergone elective total knee replacement surgery.
Treatment and prevention of recurrent deep vein thrombosis (DVT) in adults.
Treatment and prevention of pulmonary embolism (PE) in adults.
Treatment of VTE and prevention of recurrent VTE in children under 18 years.
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more of the following risk factors:
Previous stroke or transient ischaemic attack.
Symptomatic heart failure, New York Heart Association Class II or greater.
Age 75 years and above.
Diabetes mellitus.
Hypertension.
Dosage
Adults
Prevention of Venous Thromboembolism (VTE) following elective knee replacement
Treatment should be initiated with a single oral dose of 110mg dabigatran etexilate within 1 to 4 hours of completed surgery (provided clinical assessment indicates good haemostasis).
If haemostasis is not secured initiation of dabigatran etexilate treatment should be delayed.
After initiation, treatment should continue on the first day after surgery with 220mg dabigatran etexilate once daily for 10 days.
Prevention of Venous Thromboembolism (VTE) following elective hip replacement
Treatment should be initiated with a single oral dose of 110mg dabigatran etexilate within 1 to 4 hours of completed surgery (provided clinical assessment indicates good haemostasis).
If haemostasis is not secured initiation of dabigatran etexilate treatment should be delayed.
After initiation, treatment should continue on the first day after surgery with 220mg dabigatran etexilate once daily for 28 to 35 days.
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more risk factors
Recommended dose is 150mg twice a day. Therapy should be continued long term.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
The recommended dose is 150mg twice a day following treatment with a parenteral anticoagulant for at least 5 days.
The duration of therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding. Short duration of therapy (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, immobilisation) and longer durations should be based on permanent risk factors or idiopathic DVT or PE.
Elderly
Prevention of Venous Thromboembolism (VTE) following elective knee replacement
In patients 75 years and older there is limited clinical experience. These patients should be treated with caution.
Treatment should be initiated with a single oral dose of 75mg dabigatran etexilate within 1 to 4 hours of completed surgery (provided clinical assessment indicates good haemostasis).
If haemostasis is not secured initiation of dabigatran etexilate treatment should be delayed.
After initiation, treatment should continue on the first day after surgery with 150mg dabigatran etexilate once daily (taken as two 75mg capsules) for 10 days.
Prevention of Venous Thromboembolism (VTE) following elective hip replacement
In patients 75 years and older there is limited clinical experience. These patients should be treated with caution.
Treatment should be initiated with a single oral dose of 75mg dabigatran etexilate within 1 to 4 hours of completed surgery (provided clinical assessment indicates good haemostasis).
If haemostasis is not secured initiation of dabigatran etexilate treatment should be delayed.
After initiation, treatment should continue on the first day after surgery with 150mg dabigatran etexilate once daily (taken as two 75mg capsules) for 28 to 35 days.
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more risk factors
Patients aged 80 years and older: 110mg twice a day due to the increased risk of bleeding in this age group.
Patients aged 75 to 79 years: 150mg twice a day or 110mg twice a day, based on individual assessment of thromboembolic risk and the risk of bleeding.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
Patients aged 80 years and older: 110mg twice a day due to the increased risk of bleeding in this age group.
Patients aged 75 to 79 years: 150mg twice a day or 110mg twice a day, based on individual assessment of thromboembolic risk and the risk of bleeding.
Children
Treatment and prophylaxis of venous thromboembolism
For the treatment of VTE, the patient should receive parenteral anticoagulant for a minimum of 5 days prior to treatment initiation. For the prevention of recurrent VTE, treatment initiation should follow previous treatment.
During treatment, one dose should be taken in the morning and one in the evening with a dosing interval as close to 12 hours as possible.
Children weighing 11kg to 13kg (aged 8 to 9 years)
75mg twice daily.
Children weighing 13kg to 16kg (aged 8 to 11 years)
110mg twice daily.
Children weighing 16kg to 21kg (aged 8 to 14 years)
110mg twice daily.
Children weighing 21kg to 26kg (aged 8 to 16 years)
150mg twice daily.
Children weighing 26kg to 31kg (aged 8 to 18 years)
150mg twice daily.
Children weighing 31kg to 41kg (aged 8 to 18 years)
185mg twice daily.
Children weighing 41kg to 51kg (aged 8 to 18 years)
220mg twice daily.
Children weighing 51kg to 61kg (aged 8 to 18 years)
260mg twice daily.
Children weighing 61kg to 71kg (aged 8 to 18 years)
300mg twice daily.
Children weighing 71kg to 81kg (aged 8 to 18 years)
300mg twice daily.
Children weighing more than 81kg (aged 10 to 18 years)
300mg twice daily.
Patients with Renal Impairment
For creatinine clearance between 30 to 50 ml/minute in adult patients
In patients with creatinine clearance between 30 to 50 ml/minute there is limited clinical experience. These patients should be treated with caution and the following dosages have been suggested:
Prevention of Venous Thromboembolism (VTE) following elective knee replacement
Treatment should be initiated with a single oral dose of 75mg dabigatran etexilate within 1 to 4 hours of completed surgery (provided clinical assessment indicates good haemostasis).
If haemostasis is not secured initiation of dabigatran etexilate treatment should be delayed.
After initiation, treatment should continue on the first day after surgery with 150mg dabigatran etexilate once daily (taken as two 75mg capsules) for 10 days.
Prevention of Venous Thromboembolism (VTE) following elective hip replacement
Treatment should be initiated with a single oral dose of 75mg dabigatran etexilate within 1 to 4 hours of completed surgery (provided clinical assessment indicates good haemostasis).
If haemostasis is not secured initiation of dabigatran etexilate treatment should be delayed.
After initiation, treatment should continue on the first day after surgery with 150mg dabigatran etexilate once daily (taken as two 75mg capsules) for 28 to 35 days.
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more risk factors
The recommended dose is 150mg twice a day or 110mg twice daily, based on individual assessment of the thromboembolic risk and the risk of bleeding.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
The recommended dose is 150mg twice a day or 110mg twice daily, based on individual assessment of the thromboembolic risk and the risk of bleeding.
Additional Dosage Information
Switching from dabigatran etexilate to a parenteral anticoagulant in adults
Prevention of Venous Thromboembolism (VTE) in adults following elective knee or hip replacement
An interval of 24 hours should be given from the last dose of dabigatran etexilate.
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more risk factors, treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
An interval of 12 hours should be given from the last dose of dabigatran etexilate.
Switching from a parenteral anticoagulant to dabigatran etexilate in adults
Dabigatran etexilate should be given 0 to 2 hours prior to the time that the next dose of the alternative therapy would be due or at the time of discontinuation in the case of continuous treatment (e.g. intravenous unfractionated heparin).
Switching from dabigatran etexilate to vitamin K antagonist (VKA) in adults
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more risk factors, treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
Adjust the starting time of the VKA based on creatinine clearance:
Creatinine clearance equal to or greater than 50 ml/minute
Start VKA 3 days before discontinuing dabigatran etexilate.
Creatinine clearance between 30 and 50 ml/minute
Start VKA 2 days before discontinuing dabigatran etexilate.
Switching from vitamin K antagonist (VKA) to dabigatran etexilate in adults
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more risk factors, treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
Treatment with VKA should be stopped. Dabigatran etexilate can been given as soon as the International Normalised Ratio is below 2.
Switching from dabigatran etexilate to a parenteral anticoagulant in children
Treatment and prevention of Venous Thromboembolism (VTE) in children
An interval of 12 hours should be given from the last dose of dabigatran etexilate.
Switching from a parenteral anticoagulant to dabigatran etexilate in children
Treatment and prevention of Venous Thromboembolism (VTE) in children
The parenteral anticoagulant should be discontinued and dabigatran etexilate given 0 to 2 hours prior to the time that the next dose of the alternative therapy would be due or at the time of discontinuation in the case of continuous treatment (e.g. intravenous Unfractionated Heparin).
Switching from dabigatran etexilate to vitamin K antagonist (VKA) in children
Treatment and prevention of Venous Thromboembolism (VTE) in children
Treatment with VKA should be initiated 3 days before discontinuing dabigatran etexilate.
Dabigatran etexilate can impact on the International Normalised Ratio and so these values should be interpreted with caution until dabigatran etexilate has been discontinued for at least 2 days.
Switching from vitamin K antagonist (VKA) to dabigatran etexilate in children
Treatment and prevention of Venous Thromboembolism (VTE) in children
Treatment with VKA should be stopped. Dabigatran etexilate can been given as soon as the International Normalised Ratio is below 2.
Missed dose
Prevention of Venous Thromboembolism (VTE) in adults following elective knee or hip replacement
If a dose is missed it is recommended that patients continue with the remaining daily doses of dabigatran etexilate at the same time of the next day.
No double dose should be taken to make up for missed individual doses.
Treatment and prevention of Venous Thromboembolism (VTE) in children
If a dose is missed it is recommended that patients may take the missed dose up to 6 hours before the next scheduled dose. From 6 hours before to the next scheduled dose onwards, the dose must be omitted.
No double dose should be taken to make up for missed individual doses.
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more risk factors, treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
A missed dabigatran etexilate dose may still be taken up to 6 hours prior to the next scheduled dose. From 6 hours prior to the next scheduled dose, the missed dose should be omitted. No double dose should be taken to make up for missed individual doses.
Patients at risk from bleeding
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more risk factors, treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
The recommended dose of 110mg twice daily.
Dose adjustment in patients at risk of bleeding should be decided at the discretion of the physician. A coagulation test may help to identify patients with an increased bleeding risk caused by excessive dabigatran exposure. Patients with an increased risk of bleeding should be closely monitored (e.g. observed for anaemia or signs of bleeding).
Oesophagitis, gastritis or gastroesophageal reflux
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more risk factors, treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
The recommended dose of 150mg twice daily or 110mg twice daily, based on individual assessment of thromboembolic risk and risk of bleeding.
Concomitant use with strong P-glycoprotein inhibitors
Prevention of Venous Thromboembolism (VTE) following elective knee or hip replacement
Patients receiving concomitant verapamil, amiodarone and quinidine:
Treatment should be initiated with a single dose of 75mg within 1 to 4 hours of completed surgery (provided clinical assessment indicates good haemostasis).
After initiation, treatment should continue on the first day after surgery with 150mg dabigatran etexilate once daily (taken as two 75mg capsules) for 10 days following knee replacement surgery or 28 to 35 days following hip replacement surgery. Dabigatran etexilate and these medicinal products should be taken at the same time.
Patients with moderate renal impairment and being treated concomitantly with dabigatran etexilate and verapamil, a dose reduction of dabigatran to 75mg once daily should be considered.
Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation with one or more risk factors, treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
The recommended dose is 110mg twice daily in patients receiving concomitant verapamil. In this situation dabigatran etexilate and verapamil should be taken at the same time.
No dose adjustment is needed for concomitant use of amiodarone or quinidine.
Surgery (other than the indicated use during knee or hip replacement surgery)
Administration of the first dose of dabigatran etexilate should occur a minimum of two hours after a catheter is removed in patients undergoing anaesthesia with post-operative indwelling epidural catheters. These patients should be monitored for neurological signs and symptoms of spinal or epidural haematoma.
Dabigatran should be temporarily discontinued prior to acute intervention procedures.
Subacute surgery or interventions
A surgery or intervention should be delayed if possible until at least 12 hours after last dose. If surgery can not be delayed the risk of bleeding may be increased.
Elective surgery
If possible discontinue at least 24 hours before elective surgery.
The manufacturer gives the following recommendations for discontinuation of dabigatran treatment before surgery:
A) High risk of bleeding/major surgery
Creatinine clearance greater than or equal to 80 ml/minute: Discontinue treatment 2 days before procedure.
Creatinine clearance 50 to 79 ml/minute: Discontinue treatment 2 to 3 days before procedure.
Creatinine clearance 30 to 49 ml/minute:Discontinue treatment 4 days before procedure.
B) Standard risk of bleeding
Creatinine clearance greater than or equal to 80 ml/minute: Discontinue treatment 24 hours before procedure.
Creatinine clearance 50 to 79 ml/minute: Discontinue treatment 1 to 2 days before procedure.
Creatinine clearance 30 to 49 ml/minute: Discontinue treatment 2 to 3 days before procedure (greater than 48 hours).
Contraindications
Haemorrhage
Arteriovenous malformation
Breastfeeding
Coagulopathy
Gastrointestinal ulcer
Hepatic enzymes above 2 times the upper limit of normal
History of gastrointestinal ulceration
Neoplasm with increased bleeding risk
Oesophageal varices
Prosthetic heart valve requiring anticoagulant treatment
Recent central nervous system surgery
Recent central nervous system trauma
Recent intracranial haemorrhage
Recent ocular surgery
Renal impairment in adult patients - creatinine clearance below 30ml/minute
Renal impairment in children 8-18 years - eGFR below 50ml/minute/1.73m sq
Severe hepatic impairment
Vascular disorder
Precautions and Warnings
Meningitis
Patients over 74 years
Predisposition to haemorrhage
Recent organ biopsy
Recent trauma
Spinal/epidural anaesthesia
Weight above 110kg
Weight below 50kg
Antiphospholipid syndrome
Bacterial endocarditis
Encephalitis
Gastritis
Gastroesophageal reflux
Intracranial abscess
Oesophagitis
Pregnancy
Renal impairment - creatinine clearance 30-50ml/minute
Thrombocytopenia
Reduce dose in patients with creatinine clearance of 30-50ml/min
Review anticoagulant treatment prior to surgery
Consider a proton pump inhibitor to prevent gastrointestinal bleeding
Exclude clinical conditions with potential for haemorrhage before treatment
Not all available strengths are licensed for all indications
Administer at least 2 hours after removal of epidural catheter
Monitor renal function prior to initiating treatment
Monitor for bleeding during treatment
Monitor for occurrence of anaemia
Monitor renal function at least annually in patients over 75 years
Monitor renal function at least annually in patients with renal impairment
Advise patient to report gastrointestinal signs or symptoms
Reversal agent available
Discontinue if haemorrhage occurs
Discontinue if renal failure develops
Reduce dose in patients over 74 years
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment
Advise patient of risk of bleeding
Remind patient of importance of carrying Alert Card with them at all times
Although dabigatran etexilate does not generally require routine anticoagulant monitoring, the measurement of dabigatran etexilate related anticoagulation may be helpful to detect excessive high exposure to dabigatran etexilate in the presence of additional risk factors. Diluted thrombin time, ecarin clotting time and activated partial thromboplastin time may provide useful information, but results should be interpreted with caution due to inter-test variability. The International Normalised Ratio test is unreliable and should not be used.
Caution should be exercised when treatment is temporarily discontinued for interventions and anticoagulant monitoring is warranted.
When rapid reversal of the anticoagulation effect is required a specific reversal is available. Reversing dabigatran etexilate therapy exposes patients to the thrombotic risk of their underlying disease. Dabigatran treatment can be re-initiated 24 hours after administration of the reversal agent, providing adequate haemostasis has been achieved.
Use with caution in post-surgical patients with an increased risk of bleeding (e.g. those with creatinine clearance 30 to 50 ml/minute). Resume treatment in these patients after adequate haemostasis is achieved. There is limited efficacy/safety information for the use of dabigatran etexilate in patients a high surgical mortality risk and with intrinsic risk factors for thromboembolic events.
Where necessary, concomitant agents which increase the risk of haemorrhage should be administered with caution.
Anticoagulant-related nephropathy has been reported in patients taking dabigatran etexilate which may lead to complications such as compartment syndrome and acute renal failure.
This medication should not be used for hip fracture surgery.
Patients may remain on dabigatran etexilate treatment during cardioversion.
Patients may remain on dabigatran etexilate 150mg twice daily during catheter ablation for atrial fibrillation.
Direct acting Oral Anticoagulants (DOACs) including dabigatran etexilate are not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome. In particular for patients that are triple positive (for lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2-glycoprotein 1 antibodies), treatment with DOACs could be associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy.
Pregnancy and Lactation
Pregnancy
Dabigatran etexilate should be used with caution in pregnancy.
There is limited data available on the use of dabigatran etexilate in pregnant women.
Animal studies have shown reproductive toxicity. The potential risk to humans is unknown therefore the manufacturer recommends only using dabigatran etexilate is clearly necessary.
Lactation
Dabigatran etexilate is contraindicated in breastfeeding.
Women should be advised not to breastfeed during treatment with dabigatran etexilate.
Side Effects
Abdominal pain
Altered liver function tests
Anaemia
Anaphylactic reaction
Angioedema
Bronchospasm
Decrease in haematocrit
Diarrhoea
Dyspepsia
Dysphagia
Elevation of liver enzymes
Epistaxis
Gastro-intestinal haemorrhage
Gastro-intestinal ulceration
Genitourinary bleeding
Haemarthrosis
Haematoma
Haematuria
Haemoglobin decrease
Haemoptysis
Haemorrhage
Haemorrhage (injection site)
Haemorrhoidal bleeding
Hepatobiliary disorders
Hyperbilirubinaemia
Hypersensitivity reactions
Increase in ALT level
Increase in AST level
Intracranial bleeding
Myocardial infarction
Nausea
Pruritus
Rash
Rectal haemorrhage
Skin and mucosal bleeding
Thrombocytopenia
Urticaria
Vomiting
Wound haemorrhage
Wound secretion
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: January 2019
Reference Sources
Summary of Product Characteristics for Pradaxa 75mg hard capsules. Boehringer Ingelheim Ltd. Revised September 2022.
Summary of Product Characteristics for Pradaxa 110mg hard capsules. Boehringer Ingelheim Ltd. Revised September 2022.
Summary of Product Characteristics for Pradaxa 150mg hard capsules. Boehringer Ingelheim Ltd. Revised September 2022.
Direct Healthcare Professional Communication on the importance of assessing renal function treated with Pradaxa (dabigatran etexilate).
MHRA October 27, 2011
https://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con134763.pdf
Last accessed: May 7, 2013
Drug Safety Update Volume 5 Issue 12 July 2012.
Available at: https://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON175429
Last accessed: May 7, 2013.
Drug Safety Update Volume 6 Issue 8 March 2013.
Available at: https://www.mhra.gov.uk/home/groups/dsu/documents/publication/con254819.pdf
Last accessed: May 7, 2013.
Drug Safety Update Volume 7 Issue 3 October 2013.
Available at: https://www.mhra.gov.uk/home/groups/dsu/documents/publication/con322740.pdf
Last accessed: October 10, 2013.
HPRA Safety Notices May 2019
Available at: https://www.hpra.ie
Last accessed: 07 June 2019.
MHRA Drug Safety Update June 2020
Available at: https://www.mhra.gov.uk
Last accessed: 06 November 2020
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 06 December 2022
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