Dabigatran etexilate
Regulatory sources consulted
- openfda-label-4f8d4596-bc1a-48a1-8f6a-caf816a2037f
- aemps-ft-89508
- ansm-rcp-68570512
- ema-epar-EMEA/H/C/005639
- PubMed PMID:38033089 ↗
- PubMed PMID:36194215 ↗
- PubMed PMID:38035566 ↗
- PubMed PMID:39133476 ↗
- PubMed PMID:37991392 ↗
- OpenFDA · B01AE07
- RxNorm rxcui 1546356 ↗
Approved indications
- To reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation.
- For the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in adult patients who have been treated with a parenteral anticoagulant for 5 to 10 days.
- To reduce the risk of recurrence of DVT and PE in adult patients who have been previously treated.
- For the prophylaxis of DVT and PE in adult patients who have undergone hip replacement surgery.
Contraindications
Absolute
- Active pathological bleeding.
- History of a serious hypersensitivity reaction to dabigatran etexilate.
- Mechanical prosthetic heart valve.
- Severe renal impairment (CrCl < 30 ml/min) (per EU SmPC).
- Concomitant treatment with potent P-gp inhibitors: systemic ketoconazole, cyclosporine, itraconazole, dronedarone (per EU SmPC).
Clinical warnings
- Boxed warning · PREMATURE DISCONTINUATION OF DABIGATRAN INCREASES THE RISK OF THROMBOTIC EVENTS. If anticoagulation with dabigatran is discontinued for a reason other than pathological bleeding, consider coverage with another anticoagulant. — FDA
- Boxed warning · SPINAL/EPIDURAL HEMATOMA. Epidural or spinal hematomas may occur in patients treated with dabigatran who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. — FDA
Drug interactions
- HighRifampinJ04AB02
Mechanism: Potent induction of P-glycoprotein (P-gp), which drastically reduces dabigatran exposure and increases the risk of therapeutic failure (thrombosis).
Recommendation: Avoid concomitant use.
FDA labelEMA SPC
- HighKetoconazole (systemic)J02AB02
Mechanism: Potent inhibition of P-glycoprotein (P-gp), which significantly increases dabigatran exposure (AUC >2.5x) and the risk of bleeding.
Recommendation: Concomitant use is contraindicated according to European SmPCs.
EMA SPCANSM RCP
- ModerateVerapamilC08DA01
Mechanism: Moderate inhibition of P-glycoprotein (P-gp), which increases dabigatran exposure. The magnitude of the interaction depends on the timing of administration and the verapamil formulation.
Recommendation: Caution and clinical monitoring are required. The risk is increased in patients with decreased renal function. Consider separating the doses by several hours to mitigate the interaction.
FDA labelEMA SPC
Adverse events
Common (≥1%)
bleeding · dyspepsia · abdominal pain · gastritis · diarrhea
Rare but serious
major bleeding (including intracranial) · anaphylactic reaction · spinal/epidural hematoma · thrombocytopenia · gastrointestinal ulceration
Pregnancy and lactation
Pregnancy: Available data are insufficient to determine risks. Use of anticoagulants carries a risk of hemorrhage to the mother and fetus. Lactation: Breastfeeding is not recommended during treatment.
Recent literature (PubMed)
Guía de práctica clínica fundamental que actualiza las recomendaciones para el manejo de la fibrilación auricular, incluyendo la evaluación del riesgo tromboembólico y el uso de anticoagulantes como el dabigatrán.
Revisión exhaustiva sobre el manejo perioperatorio de los ACOD, incluido el dabigatrán. Propone protocolos estandarizados para suspender y reiniciar el fármaco según el riesgo de sangrado del procedimiento, con el objetivo de minimizar complicaciones trombóticas y hemorrágicas.
Revisión sobre el uso de ACOD en pacientes con enfermedad renal crónica (ERC). Analiza la evidencia para el ajuste de dosis de dabigatrán en ERC moderada y discute los datos limitados en ERC avanzada y diálisis, un área crítica para la seguridad del fármaco.
Revisión sobre el diagnóstico y manejo de la embolia pulmonar aguda. Confirma que los anticoagulantes orales directos, como el dabigatrán, son no inferiores a la terapia estándar con heparina/warfarina para el tratamiento, con un menor riesgo de sangrado.
Revisión que resume las propiedades farmacocinéticas y farmacodinámicas de los ACOD. Destaca las diferencias entre fármacos, incluyendo el perfil del dabigatrán como inhibidor directo de la trombina y su dependencia de la función renal para la eliminación.