Pradaxa Drug Interactions

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 metabolised by the cytochrome P450 system and have no in vitro effects on human cytochrome P450 enzymes. Therefore, related medicinal product interactions are notexpected with dabigatran (see Pharmacology: Pharmacokinetics: PK in specific populations under Actions).
NSAIDs: NSAIDs given for short-term perioperative analgesia have been shown not to be associated with increased bleeding risk when given in conjunction with dabigatran etexilate. With chronic use in the RE-LY study, NSAIDs increased the risk of bleeding by approximately 50% on both dabigatran etexilate and warfarin. Therefore, due to the risk of haemorrhage, notably with NSAIDs with elimination half-lives >12 hours, close observation for signs of bleeding is recommended.
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: For the concomitant use of P-gp inhibitors and dosing of PRADAXA in the indication, see Dosage & Administration and Pharmacology: Pharmacokinetics: PK in specific populations under Actions.
Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: 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: Amiodarone is an inhibitor of the efflux transporter P-glycoprotein and dabigatran etexilate a substrate of this transporter. 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). In view of the long half-life of amiodarone the potential for drug interaction may exist for weeks after discontinuation of amiodarone.
Prevention of stroke and systemic embolism in patients with non-valvular 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 (150mg) was coadministered with oral verapamil, the C_max 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).
Prevention of stroke and systemic embolism in patients with non-valvular 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 Pharmacology: Pharmacokinetics: PK in specific populations under Actions).
Clarithromycin: Dabigatan exposure in healthy subjects was increased by about 19% in the presence of clarithromycin 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 AUC_0-∞ and C_max were reduced by 67% and 66% compared to the reference treatment, respectively.
The concomitant use with P-gp inducers (e.g., rifampicin, St. John's wort (Hypericum perforatum), carbamazepine, or phenytoin) reduces exposure to dabigatran and should be avoided (see Precautions and Pharmacology: Pharmacokinetics: PK in specific populations under Actions).