|Systematic (IUPAC) name|
|Trade names||Pradaxa, Pradax, Prazaxa|
|Biological half-life||12–17 hours|
|ATC code||B01AE07 (WHO)|
|Molar mass||627.734 g/mol|
|(what is this?)|
Dabigatran (Pradaxa, Prazaxa) is an anticoagulant medication that can be taken by mouth. It is being studied for various uses and in some cases is an alternative to warfarin, since it does not have to be monitored by blood tests, but offers similar results in terms of efficacy.
In case of major bleeding, there is an antidote, idarucizumab (sold under the brand name Praxbind). A large study sponsored by the manufacturer found that idarucizumab effectively reversed anticoagulation by dabigatran within minutes.
Dabigatran is used to prevent strokes in those with atrial fibrillation not caused by heart valve issues, as well as deep vein thrombosis and pulmonary embolism in persons who have been treated for 5–10 days with parenteral anticoagulant (usually low molecular weight heparin), and to prevent deep vein thrombosis and pulmonary embolism in some circumstances.
Dabigatran is contraindicated in patients who have active pathological bleeding, since dabigatran can increase bleeding risk and can also cause serious and potentially life-threatening bleeds. Dabigatran is also contraindicated in patients who have a history of serious hypersensitivity reaction to dabigatran (e.g. anaphylaxis or anaphylactic shock). The use of dabigatran should also be avoided in patients with mechanical prosthetic heart valve due to the increased risk of thromboembolic events (e.g. valve thrombosis, stroke, and myocardial infarction) and major bleeding associated with dabigatran in this population.
The most commonly reported side effect of dabigatran is gastrointestinal upset. When compared to people anticoagulated with warfarin, patients taking dabigatran had fewer life-threatening bleeds, fewer minor and major bleeds, including intracranial bleeds, but the rate of gastrointestinal bleeding was significantly higher. Dabigatran capsules contain tartaric acid, which lowers the gastric pH and is required for adequate absorption. The lower pH has previously been associated with dyspepsia; some hypothesize that this plays a role in the increased risk of gastrointestinal bleeding.
A small but significantly increased risk of myocardial infarctions (heart attacks) has been noted when combining the safety outcome data from multiple trials.
Reduced doses should be used in those with poor kidney function.
Dabigatran has a half-life of approximately 12-14 h and exert a maximum anticoagulation effect within 2-3 h after ingestion. Fatty foods delay the absorption of dabigatran, although the bio-availability of the drug is unaffected. One study showed that absorption may be moderately decreased if taken with a proton pump inhibitor. Drug excretion through P-glycoprotein pumps is slowed in patients taking strong p-glycoprotein pump inhibitors such as quinidine, verapamil, and amiodarone, thus raising plasma levels of dabigatran.
Dabigatran (then compound BIBR 953) was discovered from a panel of chemicals with similar structure to benzamidine-based thrombin inhibitor α-NAPAP (N-alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide), which had been known since the 1980s as a powerful inhibitor of various serine proteases, specifically thrombin, but also trypsin. Addition of ethyl ester and hexyloxycarbonyl carbamide hydrophobic side chains led to the orally absorbed prodrug, BIBR 1048 (dabigatran etexilate).
On March 18, 2008, the European Medicines Agency granted marketing authorisation for Pradaxa for the prevention of thromboembolic disease following hip or knee replacement surgery and for non-valvular atrial fibrillation.
The National Health Service in Britain authorised the use of dabigatran for use in preventing blood clots in hip and knee surgery patients. According to a BBC article in 2008, Dabigatran was expected to cost the NHS £4.20 per day, which was similar to several other anticoagulants.
Initially there was no specific way to reverse the anticoagulant effect of dab