Dabiran

Reduction in Risk of Stroke and Systemic Embolism in Non-valvular AF- CrCl >30 mL/min: 150 mg twice daily CrCl 15 to 30 mL/min: 75 mg twice daily CrCl <15 mL/min or on dialysis: Dosing recommendations cannot be provided CrCl 30 to 50 mL/min with concomitant use of P-gp inhibitors: Reduce dose to 75 mg twice daily if given with P-gp inhibitors dronedarone or systemic ketoconazole. CrCl <30 mL/min with concomitant use of P-gp inhibitors: Avoid co-administration Treatment of DVT and PE, Reduction in the Risk of Recurrence of DVT and PE- CrCl >30 mL/min: 150 mg twice daily CrCl ≤30 mL/min or on dialysis: Dosing recommendations cannot be provided CrCl <50 mL/min with concomitant use of P-gp inhibitors: Avoid co-administration Prophylaxis of DVT and PE Following Hip Replacement Surgery- CrCl >30 mL/min: 110 mg for first day, then 220 mg once daily CrCl ≤30 mL/min or on dialysis: Dosing recommendations cannot be provided CrCl <50 mL/min with concomitant use of P-gp inhibitors: Avoid co-administration. Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation : For patients with creatinine clearance (CrCl) >30 mL/min, the recommended dose of Dabigatran Etexilate is 150 mg taken orally, twice daily. For patients with severe renal impairment (CrCl 15-30 mL/min), the recommended dose of Dabigatran Etexilate is 75 mg twice daily. Dosing recommendations for patients with a CrCl <15 mL/min or on dialysis cannot be provided. Treatment of Deep Venous Thrombosis and Pulmonary Embolism : For patients with CrCl >30 mL/min, the recommended dose of Dabigatran Etexilate is 150 mg taken orally, twice daily, after 5-10 days of parenteral anticoagulation. Dosing recommendations for patients with a CrCl ≤30 mL/min or on dialysis cannot be provided. Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism : For patients with CrCl >30 mL/min, the recommended dose of Dabigatran Etexilate is 150 mg taken orally, twice daily after previous treatment. Dosing recommendations for patients with a CrCl ≤30 mL/min or on dialysis cannot be provided. Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism Following Hip Replacement Surgery : For patients with CrCl >30 mL/min, the recommended dose of Dabigatran Etexilate is 110 mg taken orally 1-4 hours after surgery and after hemostasis has been achieved, then 220 mg taken once daily for 28-35 days. If Dabigatran Etexilate is not started on the day of surgery, after hemostasis has been achieved initiate treatment with 220 mg once daily. Dosing recommendations for patients with a CrCl ≤30 mL/min or on dialysis cannot be provided

Dabigatran and its acyl glucuronides are competitive, direct thrombin inhibitors. Because thrombin (serine protease) enables the conversion of fibrinogen into fibrin during the coagulation cascade, its inhibition prevents the development of a thrombus. Both free and clot-bound thrombin, and thrombin-induced platelet aggregation are inhibited by the active moieties. At recommended therapeutic doses, dabigatran etexilate prolongs the coagulation markers such as aPTT, ECT, and TT. INR is relatively insensitive to the exposure to dabigatran and cannot be interpreted the same way as used for warfarin monitoring. The aPTT test provides an approximation of Dabigatran Etexilate’s anticoagulant effect. The average time course for effects on aPTT, following approved dosing regimens in patients with various degrees of renal impairment is shown in Figure 2. The curves represent mean levels without confidence intervals; variations should be expected when measuring aPTT. While advice cannot be provided on the level of recovery of aPTT needed in any particular clinical setting, the curves can be used to estimate the time to get to a particular level of recovery, even when the time since the last dose of Dabigatran Etexilate is not precisely known. In the RE-LY trial, the median (10 th to 90 th percentile) trough aPTT in patients receiving the 150 mg dose was 52 (40 to 76) seconds.

The following clinically significant adverse reactions are described elsewhere in the labeling: Increased Risk of Thrombotic Events after Premature Discontinuation Risk of Bleeding Spinal/Epidural Anesthesia or Puncture Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves Increased Risk of Thrombosis in Patients with Triple-Positive Antiphospholipid Syndrome

Dabigatran Etexilate is contraindicated in patients with: Active pathological bleeding. History of a serious hypersensitivity reaction to Dabigatran Etexilate (e.g., anaphylactic reaction or anaphylactic shock). Mechanical prosthetic heart valve.

Bleeding : Dabigatran Etexilate can cause serious and fatal bleeding Bioprosthetic heart valves : Dabigatran Etexilate use not recommended Increased Risk of Thrombosis in Patients with Triple-Positive Antiphospholipid Syndrome : Dabigatran Etexilate use not recommended

Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation : The concomitant use of Dabigatran Etexilate with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided. P-gp inhibition and impaired renal function are the major independent factors that result in increased exposure to dabigatran. 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), reduce the dose of Dabigatran Etexilate 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, and ticagrelor does not require a dose adjustment of Dabigatran Etexilate. These results should not be extrapolated to other P-gp inhibitors. The concomitant use of Dabigatran Etexilate and P-gp inhibitors in patients with severe renal impairment (CrCl 15-30 mL/min) should be avoided. Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism : Avoid use of Dabigatran Etexilate and P-gp inhibitors in patients with CrCl <50 mL/min. Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism 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. The concomitant use of Dabigatran Etexilate and P-gp inhibitors in patients with CrCl <50 mL/min should be avoided.