2.1 Recommended Dose
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 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
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 PRADAXA is 150 mg taken orally, twice daily. For patients with severe renal impairment (CrCl 15-30 mL/min), the recommended dose of PRADAXA 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
For patients with CrCl >30 mL/min, the recommended dose of PRADAXA 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
For patients with CrCl >30 mL/min, the recommended dose of PRADAXA 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)].
2.2 Dosing Adjustments
Assess renal function prior to initiation of treatment with PRADAXA. 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, 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 patients on PRADAXA [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 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)].
2.3 Instructions to Patients
Instruct patients to swallow the capsules whole. PRADAXA 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 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 should not be doubled to make up for a missed dose.
2.4 Converting from or to Warfarin
When converting patients from warfarin therapy to PRADAXA, discontinue warfarin and start PRADAXA when the INR is below 2.0.
When converting from PRADAXA to warfarin, adjust the starting time of warfarin based on creatinine clearance as follows:
For CrCl ≥50 mL/min, start warfarin 3 days before discontinuing PRADAXA.
For CrCl 30-50 mL/min, start warfarin 2 days before discontinuing PRADAXA.
For CrCl 15-30 mL/min, start warfarin 1 day before discontinuing PRADAXA.
For CrCl <15 mL/min, no recommendations can be made.
Because PRADAXA can increase INR, the INR will better reflect warfarin’s effect only after PRADAXA has been stopped for at least 2 days [see Clinical Pharmacology (12.2)].
2.5 Converting from or to Parenteral Anticoagulants
For patients currently receiving a parenteral anticoagulant, start PRADAXA 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 patients currently taking PRADAXA, wait 12 hours (CrCl ≥30 mL/min) or 24 hours (CrCl <30 mL/min) after the last dose of PRADAXA before initiating treatment with a parenteral anticoagulant [see Clinical Pharmacology (12.3)].
2.6 Discontinuation for Surgery and Other Interventions
If possible, discontinue PRADAXA 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)].
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)].
