Pradaxa (Dabigatran Etexilate Mesylate) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Reduction of Risk of Stroke and Systemic Embolism in Non-valvularAtrial Fibrillation

The concomitant use of PRADAXA with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided [see Clinical Pharmacology ].

P-gp inhibition and impaired renal function are the major independent factors that result in increased exposure to dabigatran [see Clinical Pharmacology ]. Concomitant use of P-gp inhibitors in patients with renal impairment is expected to produce increased exposure of dabigatran compared to that seen with either factor alone.

In patients with moderate renal impairment (CrCl 30-50 mL/min), consider reducing the dose of PRADAXA to 75 mg twice daily when administered concomitantly with the P-gp inhibitors dronedarone or systemic ketoconazole. The use of the P-gp inhibitors verapamil, amiodarone, quinidine, clarithromycin, ticagrelor does not require a dose adjustment of PRADAXA. These results should not be extrapolated to other P-gp inhibitors [see Warnings and Precautions , Use in Specific Populations , and Clinical Pharmacology ].

The concomitant use of PRADAXA and P-gp inhibitors in patients with severe renal impairment (CrCl 15-30 mL/min) should be avoided [see Warnings and Precautions , Use in Specific Populations , and Clinical Pharmacology ].

Treatment and Reduction in the Risk of Recurrence of Deep VenousThrombosis and Pulmonary Embolism

Avoid use of PRADAXA and P-gp inhibitors in patients with CrCl <50 mL/min [see Warnings and Precautions , Use in Specific Populations , and Clinical Pharmacology ].

OVERDOSAGE

Accidental overdose may lead to hemorrhagic complications. There is no reversal agent for dabigatran. In the event of hemorrhagic complications, initiate appropriate clinical support, discontinue treatment with PRADAXA, and investigate the source of bleeding. Dabigatran is primarily eliminated by the kidneys with a low plasma protein binding of approximately 35%. Hemodialysis can remove dabigatran; however, data supporting this approach are limited. Using a high-flux dialyzer, blood flow rate of 200 mL/min, and dialysate flow rate of 700 mL/min, approximately 49% of total dabigatran can be cleared from plasma over 4 hours. At the same dialysate flow rate, approximately 57% can be cleared using a dialyzer blood flow rate of 300 mL/min, with no appreciable increase in clearance observed at higher blood flow rates. Upon cessation of hemodialysis, a redistribution effect of approximately 7% to 15% is seen. The effect of dialysis on dabigatran’s plasma concentration would be expected to vary based on patient specific characteristics. Measurement of aPTT or ECT may help guide therapy [see Warnings and Precautions and Clinical Pharmacology ].

CONTRAINDICATIONS

PRADAXA is contraindicated in patients with:

• Active pathological bleeding [see Warnings and Precautions and Adverse Reactions ] .
• History of a serious hypersensitivity reaction to PRADAXA (e.g., anaphylactic reaction or anaphylactic shock) [see Adverse Reactions ] .
• Mechanical prosthetic heart valve [see Warnings and Precautions ]