Dabigatran
Pradaxa
The only DOAC that directly inhibits thrombin and the only one with a specific, rapidly acting antidote — idarucizumab achieves complete reversal within minutes, which weighs heavily in patients who may need emergency surgery. The price is that approximately 80 % of absorbed drug is eliminated renally, so renal function governs treatment entirely. Dyspepsia affects one in ten patients and is the most common reason for discontinuation in clinical practice.
Creatinine clearance below 30 ml/min is an absolute contraindication — accumulation is renal and there is no alternative elimination route. Spinal or epidural puncture during ongoing treatment can cause spinal haematoma with permanent paralysis.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Atrial fibrillation | 150 mg × 2 orally | standard dose at CrCl ≥ 50 ml/min and age below 75 years |
| Atrial fibrillation, reduced dose | 110 mg × 2 orally | mandatory at age ≥ 80 years and with concurrent verapamil |
| Atrial fibrillation, individual assessment | 110 mg × 2 orally may be chosen | age 75–80 years, CrCl 30–50 ml/min, gastritis or oesophagitis, other bleeding risk |
| Venous thromboembolism | 150 mg × 2 orally after at least 5 days of parenteral anticoagulation | unlike apixaban and rivaroxaban, initial LMWH is required |
| Thromboprophylaxis after hip or knee replacement | 110 mg 1–4 h postoperatively, then 220 mg × 1 | 10 days after knee replacement, 28–35 days after hip replacement |
CrCl ≥ 50 ml/min: full dose. CrCl 30–50 ml/min: 150 mg × 2 may be given but 110 mg × 2 should be considered at bleeding risk; with concurrent verapamil give 110 mg × 2. CrCl < 30 ml/min: contraindicated. Creatinine clearance must be calculated using the Cockcroft–Gault formula before initiation, at least annually, and always during intercurrent illness that may affect renal function.
Contraindicated in hepatic disease with coagulopathy and clinically relevant bleeding risk, and when transaminases exceed twice the upper limit of normal. At Child–Pugh B no relevant increase in exposure is seen but documentation is limited.
Approved from birth for treatment of venous thromboembolism, with weight-based dosing and age-appropriate formulations (coated granules in sachets, oral solution, capsules 75/110/150 mg). eGFR below 50 ml/min/1.73 m² is a contraindication. Initiated by a paediatric coagulation unit.
The capsule must never be opened, divided, or chewed — it contains tartaric acid pellets that cause markedly increased absorption and bleeding risk if the coating is broken, making dabigatran unsuitable for patients with a nasogastric tube or swallowing difficulties. Do not choose dabigatran for patients with gastritis, reflux symptoms, or previous gastrointestinal bleeding: dyspepsia often leads to discontinuation, and the gastrointestinal bleeding risk is higher at 150 mg × 2 than with warfarin. In mechanical valve prosthesis, dabigatran is directly contraindicated.
Pharmacokinetics
- BIOAVAIL.
- 6,5 % (prodrug dabigatran etexilate)
- Vd
- 60–70 l
- t½
- 12–14 h (prolonged to 28 h at CrCl < 30)
- PROTEIN BINDING
- 35 %
- METABOLISM
- Esterases to active form, no CYP metabolism
- EXCRETION
- ~80 % renally unchanged
- SUBSTRATE
- P-glycoprotein
- ONSET
- 0,5–2 h