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Drugs, Supplies and Delivery
Dabigatran
Dabigatran, marketed under the brand name Pradaxa, is an oral anticoagulant used to prevent and treat blood clots. It belongs to a class of drugs known as direct thrombin inhibitors (DTIs), which work by directly inhibiting thrombin, a key enzyme in the blood clotting process. Dabigatran is widely prescribed due to its efficacy, predictable pharmacokinetics, and reduced need for routine monitoring compared to traditional anticoagulants like warfarin. This article provides a detailed overview of dabigatran, including its mechanism of action, uses, dosage, side effects, precautions, drug interactions, and generic names, referencing authoritative sources such as the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology
Dabigatran exerts its anticoagulant effect by directly inhibiting thrombin (factor IIa), a key enzyme in the coagulation cascade. The mechanism of action involves:
- Inhibition of Thrombin:
- Thrombin plays a central role in the conversion of fibrinogen to fibrin, the final step in blood clot formation.
- By directly inhibiting thrombin, dabigatran prevents the formation of fibrin clots.
- Anticoagulant Effect:
- Dabigatran’s action is specific to thrombin, making it a targeted anticoagulant with a lower risk of affecting other clotting factors.
- It does not require antithrombin III (unlike heparin) for its activity.
- Predictable Pharmacokinetics:
- Dabigatran has a rapid onset of action, reaching peak plasma concentrations within 1–2 hours.
It has a half-life of approximately 12–14 hours in healthy individuals, allowing for twice-daily dosing
Dabigatran is approved for the following conditions:
- Prevention of Stroke and Systemic Embolism in Atrial Fibrillation:
- Used in patients with non-valvular atrial fibrillation (NVAF) to reduce the risk of stroke and systemic embolism.
- Treatment and Prevention of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE):
- Used for the treatment of acute DVT and PE.
- Also used for the prevention of recurrent DVT and PE.
- Postoperative Thromboprophylaxis:
- Used to prevent venous thromboembolism (VTE) in patients undergoing hip or knee replacement surgery.
The dosage of dabigatran varies depending on the indication and patient-specific factors. Below are general guidelines:
- Atrial Fibrillation (Stroke Prevention):
- Standard Dose: 150 mg taken orally twice daily.
- Reduced Dose: 110 mg twice daily for patients with:
- Moderate renal impairment (CrCl 30–50 mL/min)
- High bleeding risk (e.g., elderly patients, those on antiplatelet therapy)
- Treatment of DVT and PE:
- Initial Dose: 150 mg taken orally twice daily.
- Duration: Typically 3–6 months, depending on the clinical scenario.
- Prevention of Recurrent DVT and PE:
- Standard Dose: 150 mg taken orally twice daily.
- Postoperative Thromboprophylaxis:
- Standard Dose: 110 mg taken orally 1–4 hours after surgery, followed by 220 mg once daily for 28–35 days (hip replacement) or 10 days (knee replacement).
- Administration:
- Dabigatran should be taken with or without food.
Swallow the capsule whole; do not crush or chew
Dabigatran is generally well-tolerated, but some side effects may occur. These include:
- Common Side Effects:
- Bleeding (e.g., nosebleeds, gum bleeding, bruising)
- Gastrointestinal symptoms (e.g., dyspepsia, abdominal pain, nausea)
- Less Common Side Effects:
- Headache
- Rash
- Elevated liver enzymes
- Rare but Serious Side Effects:
- Major Bleeding: Gastrointestinal bleeding, intracranial hemorrhage.
- Hypersensitivity Reactions: Rare cases of anaphylaxis or angioedema.
- Spinal/Epidural Hematoma: Especially in patients undergoing spinal procedures.
- Contraindications:
- Hypersensitivity to dabigatran or any component of the formulation.
- Active clinically significant bleeding.
- Severe renal impairment (CrCl < 30 mL/min).
- Warnings:
- Bleeding Risk: Dabigatran increases the risk of bleeding. Use with caution in patients with a history of bleeding disorders or conditions that predispose to bleeding.
- Renal Impairment: Use with caution in patients with moderate renal impairment (CrCl 30–50 mL/min). Avoid use in severe renal impairment (CrCl < 30 mL/min).
- Pregnancy and Lactation: Dabigatran is not recommended during pregnancy or breastfeeding unless the benefits outweigh the risks.
- Monitoring:
- Regular monitoring of renal function (serum creatinine).
- Watch for signs of bleeding (e.g., unusual bruising, blood in stool or urine).
Dabigatran interacts with several medications, including:
- Strong P-gp Inhibitors (e.g., ketoconazole, ritonavir): Increase dabigatran levels, increasing the risk of bleeding. Avoid concurrent use or reduce the dose of dabigatran.
- Strong P-gp Inducers (e.g., rifampin, carbamazepine): Decrease dabigatran levels, reducing its efficacy. Avoid concurrent use.
- Other Anticoagulants (e.g., warfarin, heparin): Increased risk of bleeding.
- NSAIDs (e.g., ibuprofen): Increased risk of gastrointestinal bleeding.
Antiplatelet Agents (e.g., aspirin, clopidogrel): Increased risk of bleeding
Dabigatran is available under its generic name as well as brand names. Some common formulations include:
- Generic Name: Dabigatran etexilate
Brand Name: Pradaxa (commonly used worldwide
