Definitions

Dabigatran

Dabigatran

{{drugbox | drug_name = Dabigatran etexilate | IUPAC_name = Ethyl 3-{[(2-{[(4-{N'-[(hexyloxy)carbonyl] carbamimidoyl}phenyl)amino]methyl}-1- methyl-1H-benzimidazol-5-yl)carbonyl] (2-pyridinyl)amino}propanoate | image = Dabigatran etexilate structure.svg | width = 135 | CAS_number = 211915-06-9 | CAS_supplemental = 211914-51-1 | ATC_prefix = B01 | ATC_suffix = AE07 | ATC_supplemental= | PubChem = 6445226 | DrugBank = | chemical_formula = | C=34 | H=41 | N=7 | I= | Br= | Cl= | F= | O=5 | P= | S= | Se= | Na= | charge= | molecular_weight = 627.734 (471.511 without etexilate) | specific_rotation = | sec_combustion = | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = Schedule VI | legal_UK = POM | legal_US = | legal_status = | dependency_liability = unknown | routes_of_administration = oral | licence_EU = Pradaxa }}

Dabigatran is an anticoagulant from the class of the direct thrombin inhibitors. It is being studied for various clinical indications, for some of which it may replace warfarin as the preferred anticoagulant. It is orally administered as the prodrug dabigatran etexilate (marketed as Pradaxa since April 2008 in European countries and Pradax in Canada). It was developed by pharmaceutical company Boehringer-Ingelheim.

Development

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 a hydrophobic side chain led to the orally absorbed prodrug BIBR 1048 (dabigatran etexilate).

Phase 3 clinical trials are ongoing in treatment and prevention of secondary venous thromboembolism (VTE) in post-operative orthopedic patients; long-term prophylaxis in acute coronary syndrome and stroke patients with atrial fibrillation and symptomatic VTE because of various causes (expected results by 2009-2010). In stroke prevention in patients with atrial fibrillation, it is the first drug likely to be marketed.

Dosing

A 2004 study showed a good safety profile at doses between 12.5 and 300 mg twice daily.

In a phase II study comparing dabigatran with enoxaparin showed increased efficacy in preventing thrombosis in patients undergoing orthopedic surgery, but a possible increased bleeding risk in patients receiving higher doses of dabigatran. Finally, a phase III study, comparing doses of 150 and 220 once daily with the standard dose of enoxaparin 40 mg once daily, confirmed that dabigatran performed equally well as enoxaparin in preventing thrombosis, with a similar risk profile.

Absorption is unrelated to food but may be decreased with co-administration of proton pump inhibitors.

Approval and usage

On March 18, 2008, the European Medicines Agency granted marketing authorisation for dabigatran.

The National Health Service in Britain have authorised the use of dabigatran for use in preventing blood clots in hip and knee surgery patients. Charities, including the British Heart Foundation are campaigning for the drug to be widely prescribed in place of Warfarin, which has the down side of having to be taken for at least one month, and heparin, which is administered intravenously or subcutaneously in its low molecular weight form. Dabigatran will cost the NHS £4.20 per day, which is equivalent to other anticoagulants.

In Canada, approval came on June 13, 2008.

References

External links

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