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The concomitant use of PRADAXA with treatments that act on haemostasis or coagulation including Vitamin K antagonists can markedly increase the risk of bleeding (See Precautions).
Dabigatran etexilate and dabigatran are not metabolized by the cytochrome P450 system and had no effects in vitro on human cytochrome P450 enzymes. Therefore related drug-drug interactions are not expected with dabigatran etexilate or dabigatran (see Pharmacology: Pharmacokinetics: PK in specific populations under Actions).
P-glycoprotein interactions: P-glycoprotein inhibitors: Dabigatran etexilate is a substrate for the efflux transporter P-gp. Concomitant administration of P-gp inhibitors (such as amiodarone, verapamil, quinidine, systemic ketoconazole, dronedarone, ticagrelor, clarithromycin and the fixed-dose combination glecaprevir/pibrentasvir) is expected to result in increased dabigatran plasma concentrations.
Concomitant administration of systemic ketoconazole is contraindicated.
Primary prevention of venous thromboembolic events in adult patients who have undergone elective total hip replacement surgery or total knee replacement surgery (pVTEp): For the concomitant use of P-gp inhibitors and dosing of PRADAXA in this indication, see Dosage & Administration and Pharmacology: Pharmacokinetics: PK in specific populations under Actions.
Reduction of the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (SPAF): For the P-gp inhibitors listed previously no dose adjustments are required for PRADAXA in this indication.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT, and PE in adults (DVT/PE): For the 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 Pharmacology: Pharmacokinetics: PK in specific populations under Actions).
For SPAF: 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 (150mg) was coadministered with oral verapamil, the Cmax and AUC of dabigatran were increased but the magnitude of this change differs, depending on timing of administration and formulation of verapamil (see Pharmacology: Pharmacokinetics: PK in specific populations under Actions).
For SPAF: 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 Pharmacology: Pharmacokinetics: PK in specific populations under Actions).
Clarithromycin: Dabigatan exposure in healthy subjects was increased by about 19% in the presence of clarithromycine without any clinical safety concern (see Pharmacology: Pharmacokinetics: PK in specific populations under Actions).
Ketoconazole: Dabigatran exposure was increased by 2.5 fold (+ 150%) after single and multiple doses of systemic ketoconazole (see Contraindications and Pharmacology: Pharmacokinetics: PK in specific populations under Actions).
Dronedarone: Dabigatran exposure was increased by 2.1 fold (+114%) after single or 2.4 fold (+136%) after multiple doses of dronedarone, respectively (see Pharmacology: Pharmacokinetics: PK in specific populations 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 75 mg dabigatran etexilate.
Dabigatran steady state exposure in healthy subjects was increased by 1.26 fold (+ 26 %) in the presence of ticagrelor at steady state or by 1.49 fold (+49%) when a loading dose of ticagrelor was administered simultaneously with 110 mg dabigatran etexilate. The increase in exposure was less pronounced when the 180 mg ticagrelor loading dose was given two hours after dabigatran intake (+27%).
P- glycoprotein substrate: Digoxin: In a study performed with 24 healthy subjects, when PRADAXA was coadministered with digoxin, no changes on digoxin and no clinical relevant changes on dabigatran exposure have been observed (see Pharmacology: Pharmacokinetics: PK in specific populations under Actions).
P-glycoprotein inducers: After 7 days of treatment with 600 mg rifampicin qd total dabigatran AUC0-∞ and Cmax were reduced by 67% and 66% compared to the reference treatment, respectively.
The concomitant use with P-gp inducers (e.g., rifampicin) reduces exposure to dabigatran and should be avoided (see Precautions and Pharmacology: Pharmacokinetics: PK in specific populations under Actions).
