Drug Detail:Pradaxa (Dabigatran [ da-big-a-tran ])
Generic Name: DABIGATRAN ETEXILATE MESYLATE 110mg
Dosage Form: capsule
Drug Class: Thrombin inhibitors
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 [see Clinical Pharmacology (12.3)].
Recommended PRADAXA Capsules Dose 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 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 coadministration | |
| Treatment of DVT and PE | CrCl >30 mL/min: | 150 mg twice daily |
| Reduction in the Risk of Recurrence of DVT and PE | 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 dose of PRADAXA Capsules is 150 mg taken orally, twice daily. For patients with severe renal impairment (CrCl 15-30 mL/min), the recommended dose of PRADAXA Capsules is 75 mg twice daily [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]. 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 dose of PRADAXA Capsules 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 [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
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 dose of PRADAXA Capsules 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 [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism in Adult Patients Following Hip Replacement Surgery
For patients with CrCl >30 mL/min, the recommended dose of PRADAXA Capsules 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 PRADAXA 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 [see Dosage and Administration (2.4), Use in Specific Populations (8.6) and Clinical Pharmacology (12.2, 12.3)].
Recommended PRADAXA Capsules Dose for Pediatrics
PRADAXA 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.
PRADAXA Capsules is 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 dose of PRADAXA 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 PRADAXA twice daily. Adjust the dose according to actual weight as treatment progresses [see Dosage and Administration (2.5)].
| Actual Weight (kg) | Dose (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 |
Dosage Adjustments
Adult patients with renal impairment
Assess renal function prior to initiation of treatment with PRADAXA 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 PRADAXA in patients who develop acute renal failure while on PRADAXA 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 PRADAXA Capsules [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)].
Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation
In patients with moderate renal impairment (CrCl 30-50 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 dose of PRADAXA Capsules to 75 mg twice daily [see Warnings and Precautions (5.5), Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
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 [see Warnings and Precautions (5.5), Drug Interactions (7.2) and Clinical Pharmacology (12.3)].
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 [see Dosage and Administration (2.5), Warnings and Precautions (5.5), Drug Interactions (7.3) and Clinical Pharmacology (12.2, 12.3)].
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/1.73m2 and the risk of increased exposure, avoid use of PRADAXA Capsules in these patients. Prior to the initiation of treatment with PRADAXA Capsules, estimate the glomerular filtration rate (eGFR) using the Schwartz formula: eGFR (Schwartz) = (0.413 × height in cm) / serum creatinine in mg/dL.
Treat patients with an eGFR > 50 mL/min/1.73m2 with the dose according to Table 1 [see Dosing and Administration (2.3)].
Administration
PRADAXA Capsules should be swallowed whole. PRADAXA Capsules should be taken with a full glass of water. Breaking, chewing, or emptying the contents of the capsule can result in increased exposure [see Clinical Pharmacology (12.3)].
If a dose of PRADAXA Capsules is 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 PRADAXA Capsules should not be doubled to make up for a missed dose.
Consider administration with food if gastrointestinal distress occurs with PRADAXA Capsules.
Converting from or to Warfarin
When converting patients from warfarin therapy to PRADAXA Capsules, discontinue warfarin and start PRADAXA Capsules when the INR is below 2.0.
When converting from PRADAXA Capsules to warfarin, adjust the starting time of warfarin as follows:
Adults
- For CrCl ≥50 mL/min, start warfarin 3 days before discontinuing PRADAXA Capsules.
- For CrCl 30-50 mL/min, start warfarin 2 days before discontinuing PRADAXA Capsules.
- For CrCl 15-30 mL/min, start warfarin 1 day before discontinuing PRADAXA Capsules.
- For CrCl <15 mL/min, no recommendations can be made.
Pediatrics
- For eGFR ≥50 mL/min/1.73m2, start warfarin 3 days before discontinuing PRADAXA Capsules.
- Pediatric patients with an eGFR <50 mL/min/1.73m2 have not been studied. Avoid use of PRADAXA Capsules in these patients.
Because PRADAXA Capsules can increase INR, the INR will better reflect warfarin's effect only after PRADAXA Capsules has been stopped for at least 2 days [see Clinical Pharmacology (12.2)].
Converting from or to Parenteral Anticoagulants
For adult and pediatric patients currently receiving a parenteral anticoagulant, start PRADAXA 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 PRADAXA Capsules wait 12 hours (CrCl ≥30 mL/min) or 24 hours (CrCl <30 mL/min) after the last dose of PRADAXA Capsules before initiating treatment with a parenteral anticoagulant [see Clinical Pharmacology (12.3)].
For pediatric patients currently taking PRADAXA, wait 12 hours after the last dose before switching to a parenteral anticoagulant.
Discontinuation for Surgery and Other Interventions
If possible, discontinue PRADAXA 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 [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
For pediatric patients, discontinue PRADAXA Capsules 24 hours before an elective surgery (eGFR > 80 mL/min/1.73m2) or 2 days before an elective surgery (eGFR 50-80 mL/min/1.73m2). Pediatric patients with an eGFR <50 mL/min/1.73m2 have not been studied, avoid use of PRADAXA Capsules in these patients.
If surgery cannot be delayed, there is an increased risk of bleeding [see Warnings and Precautions (5.2)]. This risk of bleeding should be weighed against the urgency of intervention [see Warnings and Precautions (5.1, 5.3)]. 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 [see Warnings and Precautions (5.2)]. Refer to the idarucizumab prescribing information for additional information. Restart PRADAXA Capsules as soon as medically appropriate.
