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The concomitant use of Pradaxa with treatments that act on haemostasis or coagulation including VKA can markedly increase the risk of bleeding. (See Precautions.)
Dabigatran etexilate and dabigatran are not metabolized by the cytochrome P-450 system and had no effects in vitro on human cytochrome P-450 enzymes. Therefore, related drug-drug interactions are not expected with dabigatran etexilate or dabigatran (see Special Populations under Pharmacokinetics under Actions).
P-gp Interactions: P-gp Inhibitors: Dabigatran etexilate is a substrate for the efflux transporter P-gp. Concomitant administration of P-gp inhibitors (eg, amiodarone, verapamil, quinidine, systemic ketoconazole, dronedarone, ticagrelor and clarithromycin) is expected to result in increased dabigatran plasma concentrations.
Concomitant administration of systemic ketoconazole is contraindicated.
Prevention of VTE Events in Patients Who Have Undergone Major Orthopaedic Surgery: For the concomitant use of P-gp inhibitors and dosing of Pradaxa in this indication (see Dosage & Administration and Special Precautions under Pharmacokinetics under Actions).
Prevention of Stroke, Systemic Embolism and Reduction of Vascular Mortality in Patients with Atrial Fibrillation: For the other P-gp inhibitors listed previously, no dose adjustments are required for Pradaxa in this indication.
Treatment and Prevention of Acute or Recurrent DVT and/or PE and Prevention of Related Death: For P-gp inhibitors listed previously, no dose adjustments are required for Pradaxa in this indication.
Amiodarone: Dabigatran exposure in healthy subjects was increased by 1.6-fold (+60%) in the presence of amiodarone (see Special Populations under Pharmacokinetics under Actions).
Prevention of Stroke, Systemic Embolism and Reduction of Vascular Mortality in Patients with Atrial Fibrillation: In patients in the RE-LY trial, concentrations were increased by no more than 14% and no increased risk of bleeding was observed.
Verapamil: When Pradaxa 150 mg was co-administered with oral verapamil, the Cmax and AUC of dabigatran were increased, but the magnitude of this change differs depending on the timing of administration and formulation of verapamil (see Special Populations under Pharmacokinetics under Actions).
Prevention of Stroke, Systemic Embolism and Reduction of Vascular Mortality in Patients with Atrial Fibrillation: In patients in the RE-LY trial, concentrations were increased by no more than 21% and no increased risk of bleeding was observed.
Quinidine: Dabigatran exposure in healthy subjects was increased by 1.5-fold (+53%) in the presence of quinidine (see Special Populations under Pharmacokinetics under Actions).
Clarithromycin: Dabigatran exposure in healthy subjects was increased by about 19% in the presence of clarithromycin without any clinical safety concern (see Special Populations under Pharmacokinetics under Actions).
Ketoconazole: Dabigatran exposure was increased by 2.5-fold (+150%) after single and multiple doses of systemic ketoconazole (see Special Populations under Pharmacokinetics under Actions and Contraindications).
Dronedarone: Dabigatran exposure was increased by 2.1-fold (+114%) after single or 2.4-fold (+136%) after multiple doses of dronedarone, respectively (see Special Populations under Pharmacokinetics under Actions).
Ticagrelor: Dabigatran exposure in healthy subjects was increased by 1.46 fold (+46%) in the presence of ticagrelor at steady state or by 1.73 fold (+73%) when a loading dose of ticagrelor was administered simultaneously with a single dose of dabigatran etexilate 75 mg.
P-gp Substrate: Digoxin: In a study performed with 24 healthy subjects, when Pradaxa was co-administered with digoxin, no changes on digoxin and no clinical relevant changes on dabigatran exposure have been observed (see Special Populations under Pharmacokinetics under Actions).
P-gp Inducers: After 7 days of treatment with rifampicin 600 mg once daily, the total dabigatran AUC0-∞ and Cmax were reduced by 67% and 66% compared to the reference treatment, respectively.
The concomitant use with P-gp inducers (eg, rifampicin) reduces exposure to dabigatran and should be avoided (see Special Populations under Pharmacokinetics under Actions and Precautions).
