Dabigatrandosage

Non-valvular Atrial Fibrillation in Adult Patients: o For patients with CrCl >30 mL/min: 150 mg orally, twice daily o For patients with CrCl 15 to 30 mL/min: 75 mg orally, twice daily

Treatment of DVT and PE in Adult Patients: o For patients with CrCl >30 mL/min: 150 mg orally, twice daily after 5 to 10 days of parenteral anticoagulation

Reduction in the Risk of Recurrence of DVT and PE in Adult Patients: o For patients with CrCl >30 mL/min: 150 mg orally, twice daily after previous treatment

Prophylaxis of DVT and PE Following Hip Replacement Surgery in Adult Patients: o For patients with CrCl >30 mL/min: 110 mg orally first day, then 220 mg once daily

Treatment of Pediatric VTE: o For pediatric patients: weight-based dosage, twice daily after at least 5 days of parenteral anticoagulant

Reduction in the Risk of Recurrence of Pediatric VTE: o For pediatric patients: weight-based dosage, twice daily after previous treatment

Dabigatran etexilate capsules are NOT substitutable on a milligram-to-milligram basis with other dabigatran etexilate dosage forms

Review recommendations for converting to or from other oral or parenteral anticoagulants

Temporarily discontinue dabigatran etexilate capsules before invasive or surgical procedures when possible, then restart promptly

2.1 Important

Dosage Information Dabigatran etexilate is available in different dosage forms and not all dosage forms are approved for the same indications and age groups. In addition, there are differences between the dosage forms with respect to dosing due to differences in bioavailability. Do not substitute different dosage forms on a milligram-to-milligram basis and do not combine more than one dosage form to achieve the total dose.

2.2 Recommended

Dabigatran Etexilate Capsules Dosage for Adults Indication Dosage 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 dosage 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 coadministration 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 coadministration 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 coadministration Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients For patients with creatinine clearance (CrCl) >30 mL/min, the recommended dosage of dabigatran etexilate capsules are 150 mg taken orally, twice daily. For patients with severe renal impairment (CrCl 15 to 30 mL/min), the recommended dosage of dabigatran etexilate capsules are 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 in Adult Patients For patients with CrCl >30 mL/min, the recommended dosage of dabigatran etexilate capsules are 150 mg taken orally, twice daily, after 5 to 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 in Adult Patients For patients with CrCl >30 mL/min, the recommended dosage of dabigatran etexilate capsules are 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 in Adult Patients Following Hip Replacement Surgery For patients with CrCl >30 mL/min, the recommended dosage of dabigatran etexilate capsules are 110 mg taken orally 1 to 4 hours after surgery and after hemostasis has been achieved, then 220 mg taken once daily for 28 to 35 days. If dabigatran etexilate capsules 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.

2.3 Recommended

Dabigatran Etexilate Capsules Dosage for Pediatrics Dabigatran etexilate capsules can be used in pediatric patients aged 8 to less than 18 years of age who are able to swallow the capsules whole. Other age-appropriate pediatric dosage forms of dabigatran etexilate are available for pediatric patients less than 8 years of age. For the treatment of VTE in pediatric patients, initiate treatment following treatment with a parenteral anticoagulant for at least 5 days. For reduction in risk of recurrence of VTE, initiate treatment following previous treatment. Dabigatran etexilate capsules are dosed orally twice daily, one dose in the morning and one dose in the evening, at approximately the same time every day. The dosing interval should be as close to 12 hours as possible. The recommended dosage of dabigatran etexilate capsules for the treatment of or reducing the risk of VTE in pediatric patients 8 to less than 18 years of age is based on the patient’s actual weight as shown in Table 1 below. Administer dabigatran etexilate capsules twice daily. Adjust the dosage according to actual weight as treatment progresses.

Table 1: Weight-Based Dabigatran Etexilate Capsules Dosage for Pediatric Patients Aged 8 to Less Than 18 Years Actual Weight (kg) Dosage (mg) Number of Capsules Needed 11 kg to less than 16 kg 75 mg twice daily one 75 mg capsule twice daily 16 kg to less than 26 kg 110 mg twice daily one 110 mg capsule twice daily 26 kg to less than 41 kg 150 mg twice daily one 150 mg capsule twice daily or two 75 mg capsules twice daily 41 kg to less than 61 kg 185 mg twice daily one 110 mg capsule plus one 75 mg capsule twice daily 61 kg to less than 81 kg 220 mg twice daily two 110 mg capsule twice daily 81 kg or greater 260 mg twice daily one 150 mg capsule plus one 110 mg capsule twice daily or one 110 mg capsule plus two 75 mg capsules twice daily

2.4 Dosage Adjustments

Adult patients with renal impairment Assess renal function prior to initiation of treatment with dabigatran etexilate capsules. Periodically assess renal function as clinically indicated (i.e., more frequently in clinical situations that may be associated with a decline in renal function) and adjust therapy accordingly. Discontinue dabigatran etexilate capsules in patients who develop acute renal failure while on dabigatran etexilate and consider alternative anticoagulant therapy. Generally, in adult patients, the extent of anticoagulation does not need to be assessed. When necessary, use aPTT or ECT, and not INR, to assess for anticoagulant activity in adult patients on dabigatran etexilate capsules. Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation In patients with moderate renal impairment (CrCl 30 to 50 mL/min), concomitant use of the P-gp inhibitor dronedarone or systemic ketoconazole can be expected to produce dabigatran exposure similar to that observed in severe renal impairment. Reduce the dosage of dabigatran etexilate capsules to 75 mg twice daily. Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism Dosing recommendations for patients with CrCl ≤30 mL/min cannot be provided. Avoid use of concomitant P-gp inhibitors in patients with CrCl <50 mL/min. Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism Following Hip Replacement Surgery Dosing recommendations for patients with CrCl ≤30 mL/min or on dialysis cannot be provided. Avoid use of concomitant P-gp inhibitors in patients with CrCl <50 mL/min. Pediatric patients with renal impairment Treatment and reduction in risk of recurrence of VTE in pediatric patients Due to lack of data in pediatric patients with eGFR < 50 mL/min/1.73 m 2 and the risk of increased exposure, avoid use of dabigatran etexilate capsules in these patients. Prior to the initiation of treatment with dabigatran etexilate capsules, estimate the glomerular filtration rate (eGFR) using the Schwartz formula: eGFR (Schwartz) = (0.413 x height in cm) / serum creatinine in mg/dL. Treat patients with an eGFR > 50 mL/min/1.73 m 2 with the dosage according to Table 1.

2.5 Administration

Dabigatran etexilate capsules should be swallowed whole. Dabigatran etexilate capsules should be taken with a full glass of water. Breaking, chewing, or emptying the contents of the capsule can result in increased exposure. If a dose of dabigatran etexilate capsules are not taken at the scheduled time, the dose should be taken as soon as possible on the same day; the missed dose should be skipped if it cannot be taken at least 6 hours before the next scheduled dose. The dose of dabigatran etexilate capsules should not be doubled to make up for a missed dose. Consider administration with food if gastrointestinal distress occurs with dabigatran etexilate capsules.

2.6 Converting from or to

Warfarin When converting patients from warfarin therapy to dabigatran etexilate capsules, discontinue warfarin and start dabigatran etexilate capsules when the INR is below 2. When converting from dabigatran etexilate capsules to warfarin, adjust the starting time of warfarin as follows: Adults For CrCl ≥50 mL/min, start warfarin 3 days before discontinuing dabigatran etexilate capsules. For CrCl 30 to 50 mL/min, start warfarin 2 days before discontinuing dabigatran etexilate capsules. For CrCl 15 to 30 mL/min, start warfarin 1 day before discontinuing dabigatran etexilate capsules. For CrCl <15 mL/min, no recommendations can be made. Pediatrics

For eGFR ≥ 50 mL/min/1.73 m 2, start warfarin 3 days before discontinuing dabigatran etexilate capsules.

Pediatric patients with an eGFR < 50 mL/min/1.73 m 2 have not been studied. Avoid use of dabigatran etexilate capsules in these patients. Because dabigatran etexilate capsules can increase INR, the INR will better reflect warfarin’s effect only after dabigatran etexilate capsules has been stopped for at least 2 days.

2.7 Converting from or to

Parenteral Anticoagulants For adult and pediatric patients currently receiving a parenteral anticoagulant, start dabigatran etexilate capsules 0 to 2 hours before the time that the next dose of the parenteral drug was to have been administered or at the time of discontinuation of a continuously administered parenteral drug (e.g., intravenous unfractionated heparin). For adult patients currently taking dabigatran etexilate capsules wait 12 hours (CrCl ≥30 mL/min) or 24 hours (CrCl <30 mL/min) after the last dose of dabigatran etexilate capsules before initiating treatment with a parenteral anticoagulant. For pediatric patients currently taking dabigatran etexilate capsules, wait 12 hours after the last dose before switching to a parenteral anticoagulant.

2.8 Discontinuation for

Surgery and Other Interventions If possible, discontinue dabigatran etexilate capsules in adults 1 to 2 days (CrCl ≥50 mL/min) or 3 to 5 days (CrCl <50 mL/min) before invasive or surgical procedures because of the increased risk of bleeding. Consider longer times for patients undergoing major surgery, spinal puncture, or placement of a spinal or epidural catheter or port, in whom complete hemostasis may be required. For pediatric patients, discontinue dabigatran etexilate capsules 24 hours before an elective surgery (eGFR > 80 mL/min/1.73 m 2 ) or 2 days before an elective surgery (eGFR 50 to 80 mL/min/1.73 m 2 ). Pediatric patients with an eGFR <50 mL/min/1.73 m 2 have not been studied, avoid use of dabigatran etexilate capsules in these patients. If surgery cannot be delayed, there is an increased risk of bleeding. This risk of bleeding should be weighed against the urgency of intervention. Use a specific reversal agent (idarucizumab) in case of emergency surgery or urgent procedures when reversal of the anticoagulant effect of dabigatran is needed in adults. Efficacy and safety of idarucizumab have not been established in pediatric patients. Refer to the idarucizumab prescribing information for additional information. Restart dabigatran etexilate capsules as soon as medically appropriate.