Dabigatran Etexilate Mesylate
Indications
Dabigatran Etexilate Mesylate is a direct thrombin inhibitor indicated:
- To reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.
- For the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have been treated with a parenteral anticoagulant for 5-10 days.
- To reduce the risk of recurrence of DVT and PE in patients who have been previously treated.
- For the prophylaxis of DVT and PE in patients who have undergone hip replacement surgery.
Pharmacology
Dabigatran and its acyl glucuronides are competitive, direct thrombin inhibitors. Because thrombin (serine protease) enables the conversion of fibrinogen into fibrin during the coagulation cascade, its inhibition prevents the development of a thrombus. Both free and clot-bound thrombin, and thrombin-induced platelet aggregation are inhibited by the active moieties.
Dosage & Administration
Reduction in the risk of Stroke and Systemic Embolism in Patients with Non-valvular Atrial Fibrillation:
Reduction in the Risk of Recurrence of DVT and PE: For patients with CrCl >30 mL/min: 150 mg orally,
twice daily after previous treatment.
Prophylaxis of DVT and PE Following Hip Replacement Surgery: For patients with CrCl >30 mL/min: 110 mg orally first day, then 220 mg once daily. Temporarily discontinue Dabigatran Etexilate Mesylate before invasive or surgical procedures when possible, then restart promptly.
Pediatric Use: Safety and effectiveness of Dabigatran Etexilate in pediatric patients have not been established.
Geriatric Use: Of the total number of patients in the RE-LY study, 82% were 65 and over, while 40% were 75 and over. The risk of stroke and bleeding increases with age, but the risk-benefit profile is favorable in all age groups.
- For patients with CrCl >30 mL/min: 150 mg orally, twice daily
- For patients with CrCl 15-30 mL/min: 75 mg orally, twice daily
Reduction in the Risk of Recurrence of DVT and PE: For patients with CrCl >30 mL/min: 150 mg orally,
twice daily after previous treatment.
Prophylaxis of DVT and PE Following Hip Replacement Surgery: For patients with CrCl >30 mL/min: 110 mg orally first day, then 220 mg once daily. Temporarily discontinue Dabigatran Etexilate Mesylate before invasive or surgical procedures when possible, then restart promptly.
Pediatric Use: Safety and effectiveness of Dabigatran Etexilate in pediatric patients have not been established.
Geriatric Use: Of the total number of patients in the RE-LY study, 82% were 65 and over, while 40% were 75 and over. The risk of stroke and bleeding increases with age, but the risk-benefit profile is favorable in all age groups.
Interaction
Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation: The concomitant use of Dabigatran Etexilate with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided.
Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism: Avoid use of Dabigatran Etexilate and P-gp inhibitors in patients with CrCl <50 mL/min.
Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism Following Hip Replacement Surgery: In patients with CrCl ≥50 mL/min who have concomitant administration of P-gp inhibitors such as dronedarone or systemic ketoconazole, it may be helpful to separate the timing of administration of dabigatran and the P-gp inhibitor by several hours. The concomitant use of Dabigatran Etexilate and P-gp inhibitors in patients with CrCl <50 mL/min should be avoided.
Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism: Avoid use of Dabigatran Etexilate and P-gp inhibitors in patients with CrCl <50 mL/min.
Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism Following Hip Replacement Surgery: In patients with CrCl ≥50 mL/min who have concomitant administration of P-gp inhibitors such as dronedarone or systemic ketoconazole, it may be helpful to separate the timing of administration of dabigatran and the P-gp inhibitor by several hours. The concomitant use of Dabigatran Etexilate and P-gp inhibitors in patients with CrCl <50 mL/min should be avoided.
Contraindications
Dabigatran Etexilate is contraindicated in patients with active pathological bleeding, patients with history of
serious hypersensitivity reaction to Dabigatran Etexilate and patients with mechanical prosthetic heart valve.
serious hypersensitivity reaction to Dabigatran Etexilate and patients with mechanical prosthetic heart valve.
Side Effects
Premature discontinuation of Dabigatran Etexilate increases the risk of thrombotic events. Dabigatran Etexilate increases the risk of bleeding and can cause significant and, sometimes, fatal bleeding. Common side effects of Dabigatran Etexilate include indigestion, upset stomach, or burning, stomach pain. In some people Dabigatran Etexilate can cause symptoms of an allergic reaction.
Pregnancy & Lactation
Safety has not been established during pregnancy. Breastfeeding is not recommended during treatment with Dabigatran Etexilate.
Precautions & Warnings
Premature discontinuation of Dabigatran Etexilate increases the risk of thrombotic events. Dabigatran Etexilate increases the risk of bleeding and can cause significant and, sometimes, fatal bleeding. Epidural or spinal hematomas may occur in patients treated with Dabigatran Etexilate who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. The use of Dabigatran Etexilate is contraindicated in patients with mechanical prosthetic valves. The concomitant use of Dabigatran Etexilate with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided. For patients with triple-positive antiphospholipid syndrome, treatment with Dabigatran Etexilate increases the risk of thrombosis.
Overdose Effects
Accidental overdose may lead to hemorrhagic complications. In the event of hemorrhagic complications, appropriate clinical support must be initiated, treatment with Dabigatran Etexilate should be discontinued, and the source of bleeding should be investigated. A specific reversal agent (idarucizumab) is available.
Therapeutic Class
Anti-coagulants, Anti-platelet drugs, Fibrinolytics (Thrombolytics)
Storage Conditions
Store at temperature not exceeding 30°C in dry place. Protect from light and moisture.
