Indicated for:

Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients:

• To reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation.

Treatment of Deep Venous Thrombosis and Pulmonary Embolism in Adult Patients:

• The treatment of deep venous thrombosis and pulmonary embolism in adult patients who have been treated with a parenteral anticoagulant for 5-10 days.

Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism in Adult Patients:

• To reduce the risk of recurrence of deep venous thrombosis and pulmonary embolism in adult patients who have been previously treated.

Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism in Adult Patients Following Hip Replacement Surgery:

•The prophylaxis of deep vein thrombosis and pulmonary embolism, in adult patients who have undergone hip replacement surgery.

Treatment of Venous Thromboembolic Events in Pediatric Patients:

• The treatment of venous thromboembolic events (VTE) in pediatric patients 8 to less than 18 years of age who have been treated with a parenteral anticoagulant for at least 5 days.

Reduction in the Risk of Recurrence of Venous Thromboembolic Events in Pediatric Patients:

• To reduce the risk of recurrence of VTE in pediatric patients 8 to less than 18 years of age who have been previously treated.

Safety and effectiveness of PRADAXA Capsules have not been established in pediatric patients with non-valvular atrial fibrillation or those who have undergone hip replacement surgery.

Premature discontinuation of any oral anticoagulant, including PRADAXA, increases the risk of thrombotic events. If anticoagulation with PRADAXA is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.

Epidural or spinal hematomas may occur in patients treated with PRADAXA who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

• use of indwelling epidural catheters
• concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
• a history of traumatic or repeated epidural or spinal punctures
• a history of spinal deformity or spinal surgery
• optimal timing between the administration of PRADAXA and neuraxial procedures is not known

PRADAXA is contraindicated in patients with active pathological bleeding or with mechanical prosthetic heart valves.

The use of PRADAXA for the prophylaxis of thromboembolic events in patients with atrial fibrillation in the setting of other forms of valvular heart disease, including the presence of a bioprosthetic heart valve, has not been studied and is not recommended.

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.

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.

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). Risk factors for bleeding include the concomitant use of other drugs that increase the risk of bleeding (e.g., antiplatelet agents, heparin, fibrinolytic therapy, and chronic use of NSAIDs). PRADAXA anticoagulant activity and half-life are increased in patients with renal impairment.

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. Refer to the idarucizumab prescribing information for additional information. Restart PRADAXA as soon as medically appropriate.

A specific reversal agent (idarucizumab) for dabigatran is available when reversal of the anticoagulant effect of dabigatran is needed: for emergency surgery/urgent procedures and in life-threatening or uncontrolled bleeding.

Hemodialysis can remove dabigatran; however the clinical experience supporting the use of hemodialysis as a treatment for bleeding is limited. 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.

Patients on PRADAXA 150 mg had an increased incidence of gastrointestinal adverse reactions.

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. Dosing recommendations for patients with a CrCl <15 mL/min or on dialysis cannot be provided.

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.

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.

The dose of PRADAXA should not be doubled to make up for a missed dose.

Direct-acting oral anticoagulants (DOACs), including PRADAXA, are not recommended for use in patients with triple-positive antiphospholipid syndrome (APS). For patients with APS (especially those who are triple-positive [positive for lupus anticoagulant, anticardiolipin, and anti-beta 2-glycoprotein I antibodies]), treatment with DOACs has been associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy.

The concomitant use of PRADAXA with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided.

Avoid use of concomitant P-gp inhibitors in patients with CrCl <50 mL/min.

When converting patients from warfarin therapy to PRADAXA, discontinue warfarin and start PRADAXA when the INR is below 2.0.

Because PRADAXA can increase INR, the INR will better reflect warfarin’s effect only after PRADAXA has been stopped for at least 2 days.

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.

Reduce the dose of PRADAXA to 75 mg twice daily when dronedarone or systemic ketoconazole is co-administered with PRADAXA in patients with moderate renal impairment (CrCl 30-50 mL/min).

The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including Pradaxa should be assessed in females of reproductive potential and those with abnormal uterine bleeding.

The limited available data on PRADAXA use in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes. Animal studies: delayed or irregular ossification of fetal skull bones and vertebrae and excess vaginal/uterine bleeding close to parturition.

Use of anticoagulants, including PRADAXA, may increase the risk of bleeding in the fetus and neonate.

Breastfeeding is not recommended during treatment with PRADAXA.

GoToSource

• Use in patients under 8 years of age. GoToSource

• Valvular atrial fibrillation. GoToSource

Acute kidney failure. GoToSource

Thromboembolic complications including strokes and transient ischemic attacks with periprocedural use for AF ablation. GoToSource

Gastrointestinal hemorrhage. GoToSource

Increased postoperative wound leakage. GoToSource

Pradaxa users more likely to experience strokes, heart attacks, and blood clots forming on the mechanical heart valves than were users of the anticoagulant warfarin. GoToSource

Intracranial hemorrhage. GoToSource

Hyperkalemia (high blood potassium level), pustular eruptions and drug-induced lupus. GoToSource

Increased risk of thrombosis in antiphospholipid syndrome patients. GoToSource

Esophageal ulcers. GoToSource

Lawsuits filed for internal bleeding, death and heart attacks.