dabigatran

7 DRUG INTERACTIONS • P-gp inducers: Avoid coadministration with dabigatran etexilate capsules ( 5.5 ) • P-gp inhibitors in adult patients with CrCl 30 to 50 mL/min: Reduce dosage or avoid ( 7 ) • P-gp inhibitors in adult patients with CrCl <30 mL/min: Not recommended ( 7 ) 7.1 Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients The concomitant use of dabigatran etexilate with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided [see Clinical Pharmacology (12.3)] .

Mechanism: Rifampin triggers a protein in the body that pumps dabigatran out of your system faster than normal. This lowers the amount of medicine in your blood, making it less effective at preventing dangerous blood clots.

dabigatran See Pharmacokinetics, Clinical Drug Interaction Studies (12.3) . ↑ dabigatran Increased bleeding risk with dabigatran. Depending on dabigatran indication and renal function, reduce dose of dabigatran or avoid concomitant use.

Mechanism: Ritonavir increases the amount of dabigatran in your system, which makes your blood thinner than it should be. This significantly raises your risk of internal or external bleeding.

Table 3: Drugs that Can Increase the Risk of Bleeding Drug Class Specific Drugs Anticoagulants argatroban, dabigatran, bivalirudin, desirudin, heparin, lepirudin Antiplatelet Agents aspirin, cilostazol, clopidogrel, dipyridamole, prasugrel, ticlopidine Non-steroidal Anti-Inflammatory Agents celecoxib, diclofenac, diflunisal, fenoprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, naproxen, oxaprozin, piroxicam, sulindac Serotonin Reuptake Inhibitors citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline,...

Mechanism: Both drugs are powerful blood thinners used to prevent clots. Taking them at the same time greatly increases the risk of dangerous bleeding.

In patients with moderate renal impairment (CrCl 30 to 50 mL/min), reduce the dosage of dabigatran etexilate to 75 mg twice daily when administered concomitantly with the P-gp inhibitors dronedarone or systemic ketoconazole. 7.3 Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism in Adult Patients Following Hip Replacement Surgery In patients with CrCl ≥50 mL/min who have concomitant administration of P-gp inhibitors such as dronedarone or systemic ketoconazole, it may be helpful to separate the timing of administration of dabigatran and the P-gp inhibitor by several hours.

Mechanism: Ketoconazole blocks a protein that helps the body get rid of dabigatran, which can cause the drug to build up. This is more likely to happen if your kidneys are not working at full strength.

The use of the P-gp inhibitors verapamil, amiodarone, quinidine, clarithromycin, and ticagrelor does not require a dosage adjustment of dabigatran etexilate.

Mechanism: Verapamil can slightly change how dabigatran is processed by the body, but the effect is not strong enough to be a concern.

CGMP Deviations: Detection of N-nitroso-dabigatran (NDAB) impurity levels above the Acceptable Daily Intake Limit.

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