Dabigatran etexilate

Dabigatran is used to prevent strokes in patients with atrial fibrillation not caused by heart valve problems, as well as deep vein thrombosis and pulmonary embolism in individuals who have been treated for 5-10 days with a parenteral anticoagulant (usually low molecular weight heparin ), and to prevent deep vein thrombosis and pulmonary embolism in some cases. ^[3]

It is as effective as warfarin in preventing non-hemorrhagic strokes and embolic events in patients with atrial fibrillation not due to valve problems. ^[four]

Dabigatran is contraindicated in patients who have active pathological bleeding, since dabigatran can increase the risk of bleeding, and can also cause serious and potentially life-threatening bleeding. ^[5] Dabigatran is also contraindicated in patients who have a history of serious hypersensitivity reactions to dabigatran (eg, anaphylaxis or anaphylactic shock). the use of dabigatran should also be avoided in patients with mechanical prosthetic heart valves due to the increased risk of thromboembolic events (e.g., valve, thrombosis, stroke and myocardial infarction ) and massive bleeding associated with dabigatran in this population. ^{[6] [7]}

The most commonly reported side effect of dabigatran is an upset gastrointestinal tract. Compared to people using warfarin, patients taking dabigatran had less life-threatening bleeding, less often small and large bleeding, including intracranial bleeding, but the frequency of gastrointestinal bleeding was significantly higher. Dabigatran capsules contain tartaric acid, which lowers the pH of the stomach and is necessary for proper absorption. Low pH has previously been associated with dyspepsia ; some suggest that this plays a role in the increased risk of gastrointestinal bleeding. ^[8]

The risk of myocardial infarction (heart attacks) is increased. ^[9]

Dabigatran has a half-life of about 12-14 hours, has a maximum effect within 2-3 hours after administration. ^[10] Fatty foods delay the absorption of dabigatran, although the bioavailability of the drug does not change. one study showed that absorption can be moderately reduced when taken with proton pump inhibitors. ^{[11] The} excretion of the drug with P-glycoprotein slows down in patients taking strong inhibitors such as quinidine , verapamil and amiodarone , which increases plasma levels of dabigatran. ^[12]

Dabigatran (BIBR compounds 953) was found in a group of chemicals with a similar structure in the benzamidine base of thrombin, an α-NAPAP inhibitor ( H- Alpha- (2-naphthylsulfonylglycyl) -4-amidinophenylalanine piperidide), which has been known since the 1980s as a powerful inhibitor of various serine proteases , in particular thrombin, as well as trypsin . The addition of ethyl ester and hexylocarbamide hydrophobic side chains led to the bioavailability of the prodrug , BIBR 1048 (dabigatran etexilate). ^[13]

On March 18, 2008, the European Medicines Agency issued a registration certificate for Etexilate for the prevention of thromboembolic diseases after endoprosthetics of the hip or knee joint and for non-valve atrial fibrillation. ^[fourteen]

The UK National Health Service has approved the use of dabigatran for the prevention of blood clots in the femur and knee joints of patients. According to a BBC article in 2008, Dabigatran is expected to cost nhs £ 4.20 a day, which looked like several other anticoagulants . ^[fifteen]

Initially, there was no definite way to reverse the anticoagulant effect of dabigatran in case of major bleeding. ^{[16] [17]} unlike warfarin, ^{[18] the} antidote dabigatran idarucizumab was approved by the FDA in 2015. ^[19]

Etexilate received a Compliance Notice (NLC) from the Department of Health Canada on June 10, 2008, ^[20] for the prevention of blood clots in patients undergoing hip replacement or a complete knee replacement surgery. Approvals for patients with atrial fibrillation risk of stroke came in October 2010. ^{[21] [22]}

In the US, the Food and Drug Administration (FDA) approved Etexilate on October 19, 2010, for the prevention of stroke in patients with non-valve atrial fibrillation. ^{[23] [24] [25] [26]} , albeit with some limitations. ^[27]

. ^[28]

In May 2014, the Office announced the results of a large study of dabigatran versus warfarin in 134,000 patients. The agency concluded that dabigatran is associated with a lower risk of overall mortality, ischemic stroke, and cerebral hemorrhage than warfarin. Gastrointestinal bleeding was more common in patients receiving dabigatran than in patients receiving warfarin. The risk of a heart attack was similar between the two drugs. The agency reiterated its view that dabigatran is generally beneficial. ^[29]

On July 26, 2014, British Medical Journal (bmj's) published a series of investigations that accused Beringer of hiding important information about the need for monitoring to protect patients from severe bleeding, especially in older people. ^{[30] [31]}

In August 2015, a study showed that the drug Idarucizumab can block the anticoagulant effect of dabigatran for several minutes. ^[32] Idarucizumab was approved in October 2015.