Dabigatran

Orally administrable, non-peptidic hirudin analogue which, together with Apixaban, rivaroxaban as factor Xa inhibitors, belongs to the group of "new oral, direct-acting anticoagulants".

Dabigatran is a reversible direct oral thrombin inhibitor. Dabigatran inhibits both free and fibrin-bound thrombin and thrombin-induced platelet aggregation.

The oral drug is administered as an inactive prodrug called "dabigatran etexilate". Dabigatran etexilate is converted into the active dabigatran in the plasma in the liver by esterases. The reaction is independent of CYP450. The maximum plasma concentration is reached 0.5 - 2 hours after ingestion. Dabigatran has a half-life of 11-14 hours.

Hirudin analogues bind with high affinity to the catalytic centre and the substrate recognition domain of the protease thrombin and thus behave like competitive inhibitors of the enzyme. They strongly prolong thrombin time and moderately prolong aPTT. The drugs are excreted metabolically and renally.

Prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation Treatment of adult patients with deep vein thrombosis and/or pulmonary embolism after prior treatment with fractionated or unfractionated heparin for 5 days and prevention of recurrent deep vein thrombosis and/or pulmonary embolism.

Not to be used by pregnant women and nursing mothers. Do not use during the breastfeeding period.

According to the technical information. Dabigatran is usually taken in the morning and evening independently of meals.

See below for details:

Common (≥ 1/100, < 1/10) ADRs: Anemia, nosebleed, gastrointestinal bleeding, abdominal pain, diarrhea, dyspepsia, nausea. Occasionally ( ≥ 1/1000, < 1/100): thrombocytopenia, drug hypersensitivity, rash, intracranial bleeding, hematoma, hemoptysis, rectal/hemorrhoidal bleeding, gastrointestinal ulcers, gastroesophagitis, vomiting, pathological liver function, dysphagia, skin bleeding. Rare (≥ 1/10.000, < 1/1000): Urticaria, hyperbilirubinaemia, haemarthrosis, urogenital haemorrhage, haematuria.

The simultaneous intake of P-glycoprotein inhibitors (e.g. amiodarone, verapamil, quinidine, ketoconazole and clarithromycin) leads to increased dabigatran levels. If P-glycoprotein inducers such as rifampicin, St. John's wort, carbamazepine or phenytoin are taken at the same time, dabigatran levels decrease.

Hypersensitivity to the active substance or any of the other ingredients. Patients with severe renal insufficiency. Acute clinically relevant bleeding. Organ damage that increases the risk of bleeding, spontaneous or pharmacologically induced restriction of hemostasis, impairment of liver function, liver disease, concomitant systemic administration of ketoconazole, ciclosporin, itraconazole or tacrolimus. For further contraindications see Technical Information. There is no approval for children and adolescents.

Pradaxa®

Since the beginning of 2016, a specific antidote has been available to counteract the effects of dabigatran in an emergency. This is the humanised antibody fragment Idarucizumab.