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)].
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.
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:
- 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.
- 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)].
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.
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.
150 mg capsules with a light blue opaque cap imprinted in black with the Boehringer Ingelheim company symbol and a white opaque body imprinted in black with “R150”.
110 mg capsules with a light blue opaque cap imprinted in black with the Boehringer Ingelheim company symbol and a light blue opaque body imprinted in black with “R110”.
75 mg capsules with a white opaque cap imprinted in black with the Boehringer Ingelheim company symbol and a white opaque body imprinted in black with “R75”.
PRADAXA is contraindicated in patients with:
- Active pathological bleeding [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)]
- History of a serious hypersensitivity reaction to dabigatran, dabigatran etexilate, or to one of the excipients of the product (e.g., anaphylactic reaction or anaphylactic shock) [see Adverse Reactions (6.1)]
- Mechanical prosthetic heart valve [see Warnings and Precautions (5.4)]
Premature discontinuation of any oral anticoagulant, including PRADAXA, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. If PRADAXA Capsules is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant and restart PRADAXA Capsules as soon as medically appropriate [see Dosage and Administration (2.6, 2.7, 2.8)].
PRADAXA increases the risk of bleeding and can cause significant and, sometimes, fatal bleeding. Promptly evaluate any signs or symptoms of blood loss (e.g., a drop in hemoglobin and/or hematocrit or hypotension). Discontinue PRADAXA Capsules in patients with active pathological bleeding [see Dosage and Administration (2.4)].
Risk factors for bleeding include the concomitant use of other drugs that increase the risk of bleeding (e.g., anti-platelet agents, heparin, fibrinolytic therapy, and chronic use of NSAIDs). PRADAXA’s anticoagulant activity and half-life are increased in patients with renal impairment [see Clinical Pharmacology (12.2)].
Reversal of Anticoagulant Effect:
In adults, a specific reversal agent (idarucizumab) for PRADAXA is available when reversal of the anticoagulant effect of dabigatran is needed:
- For emergency surgery/urgent procedures
- In life-threatening or uncontrolled bleeding
In pediatric patients, the efficacy and safety of idarucizumab have not been established.
Hemodialysis can remove dabigatran; however the clinical experience supporting the use of hemodialysis as a treatment for bleeding is limited [see Overdosage (10)]. Prothrombin complex concentrates, or recombinant Factor VIIa may be considered but their use has not been evaluated in clinical trials. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of dabigatran. Consider administration of platelet concentrates in cases where thrombocytopenia is present or long-acting antiplatelet drugs have been used.
When neuraxial anesthesia (spinal/epidural anesthesia) or spinal puncture is employed, patients treated with anticoagulant agents are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis [see Boxed Warning].
To reduce the potential risk of bleeding associated with the concurrent use of PRADAXA and epidural or spinal anesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of dabigatran [see Clinical Pharmacology (12.3)]. Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of dabigatran is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known.
Should the physician decide to administer anticoagulation in the context of epidural or spinal anesthesia/analgesia or lumbar puncture, monitor frequently to detect any signs or symptoms of neurological impairment, such as midline back pain, sensory and motor deficits (numbness, tingling, or weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to immediately report if they experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae.
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