REVERSING PRADAXA:

Reversing PRADAXA

When reversal of the anticoagulant effects of dabigatran is needed1

Reversal of the anticoagulant effects of dabigatran flowchart

Additional Considerations

PRAXBIND4

  • Normalization of serious bleeding observed as early as 12 min after administration (Group A: 48 of 66 patients in Group A were evaluable; 44 of 48 patients had normalization of bleeding within 72 hours)§||
    • Median time to bleeding cessation: 9.8 hours
      • Range: 0.2 hours to 62 days
  • 92% of patients who underwent an urgent procedure or emergency surgery had normal blood clotting (Group B: 52 of 52 patients in Group B were evaluable; 48 of 52 patients had normal blood clotting)

Clinical relevance of findings from Groups A and B is undetermined.§

PRADAXA6

  • Half‑life of Pradaxa® (dabigatran etexilate) in healthy subjects is 12‑17 hours
  • Anticoagulant effect and half‑life of PRADAXA are increased in patients with renal impairment
  • Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of PRADAXA
  • If surgery cannot be delayed, there is an increased risk of bleeding and this risk should be weighed against the urgency of the intervention
  • PRAXBIND has no effect on other anticoagulant or antithrombotic therapies1

Restarting PRADAXA1

Patients being treated with PRADAXA therapy have underlying disease states that predispose them to thromboembolic events. Reversing PRADAXA therapy exposes patients to the thrombotic risk of their underlying disease. To reduce this risk, resumption of anticoagulant therapy should be considered as soon as medically appropriate.

PRAXBIND is a specific reversal agent for PRADAXA, with no impact on the effect of other anticoagulant or antithrombotic therapies.

PRADAXA can be re-initiated after 24 hours following PRAXBIND administration.

These recommendations are not intended to replace clinical judgment or to dictate individual patient care.

Click here to learn more about PRADAXA.

*Emergency surgery or urgent procedure is defined as a procedure that cannot be delayed for a minimum of 8 hours.5
Life-threatening or uncontrolled bleeding is defined as overt bleeding that is judged by the treating clinician to require a reversal agent.5
§Cessation and normalization assessments were subjective and based upon investigator visualization or measurement.
||Click here to learn about the RE-VERSE AD trial.

References: 1. PRAXBIND [Prescribing Information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 2. Wann LS, Curtis AB, Ellenbogen KA et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on dabigatran): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2011;57(11):1330-1337. 3. January CT, Wann LS, Alpert S, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association. Circulation. 2014;130(23):e199-e267; e272–e274 [Correction]. 4. Data on file. Boehringer Ingelheim Pharmaceuticals, Inc. 5. Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373(6):511-520; 1-19 [suppl appendix]. 6. PRADAXA [Prescribing Information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.

IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR PRADAXA

WARNING: (A) PREMATURE DISCONTINUATION OF PRADAXA INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA

(A) PREMATURE DISCONTINUATION OF PRADAXA INCREASES THE RISK OF THROMBOTIC EVENTS

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

(B) SPINAL/EPIDURAL HEMATOMA

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

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients who are or will be anticoagulated.

CONTRAINDICATIONS

PRADAXA is contraindicated in patients with:
  • active pathological bleeding;
  • known serious hypersensitivity reaction (e.g., anaphylactic reaction or anaphylactic shock) to PRADAXA;
  • mechanical prosthetic heart valve

WARNINGS & PRECAUTIONS

Increased Risk of Thrombotic Events after Premature Discontinuation

Premature discontinuation of any oral anticoagulant, including PRADAXA, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. If PRADAXA is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant and restart PRADAXA as soon as medically appropriate.

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). Discontinue PRADAXA in patients with active pathological bleeding.
  • Risk factors for bleeding include concomitant use of medications 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.
  • Reversal of Anticoagulant Effect: A specific reversal agent (idarucizumab) for dabigatran is available when reversal of the anticoagulant effect of dabigatran is needed:
    • For emergency surgery/urgent procedures
    • In life-threatening or uncontrolled bleeding
    Hemodialysis can remove dabigatran; however clinical experience for 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. Protamine sulfate and vitamin K are not expected to affect dabigatran anticoagulant activity. Consider administration of platelet concentrates where thrombocytopenia is present or long-acting antiplatelet drugs have been used.

Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves

The use of PRADAXA is contraindicated in patients with mechanical prosthetic valves due to a higher risk for thromboembolic events, especially in the post-operative period, and an excess of major bleeding for PRADAXA vs. warfarin. Use of PRADAXA for the prophylaxis of thromboembolic events in patients with AFib in the setting of other forms of valvular heart disease, including bioprosthetic heart valve, has not been studied and is not recommended.

Effect of P-gp Inducers & Inhibitors on Dabigatran Exposure

Concomitant use of PRADAXA with P‑gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided. P‑gp inhibition and impaired renal function are major independent factors in increased exposure to dabigatran. Concomitant use of P‑gp inhibitors in patients with renal impairment is expected to increase exposure of dabigatran compared to either factor alone.

Reduction of Risk of Stroke/Systemic Embolism in NVAF

  • For patients with moderate renal impairment (CrCl 30‑50 mL/min), reduce the dose of PRADAXA to 75 mg twice daily when dronedarone or systemic ketoconazole is coadministered with PRADAXA.
  • For patients with severe renal impairment (CrCl 15‑30 mL/min), avoid concomitant use of PRADAXA and P‑gp inhibitors.

Treatment and Reduction in the Risk of Recurrence of DVT/PE & Prophylaxis of DVT/PE Following Hip Replacement Surgery

  • For patients with CrCl <50 mL/min, avoid use of PRADAXA and concomitant P‑gp inhibitors

ADVERSE REACTIONS

The most serious adverse reactions reported with PRADAXA were related to bleeding.

Other Measures Evaluated

In NVAF patients, a higher rate of clinical MI was reported in patients who received PRADAXA (0.7/100 patient-years for 150 mg dose) than in those who received warfarin (0.6).

INDICATIONS AND USAGE

Pradaxa® (dabigatran etexilate mesylate) capsules is indicated:

  • to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation;
  • for the treatment of deep venous thrombosis and pulmonary embolism in patients who have been treated with a parenteral anticoagulant for 5-10 days;
  • to reduce the risk of recurrence of deep venous thrombosis and pulmonary embolism in patients who have been previously treated
  • for the prophylaxis of deep vein thrombosis and pulmonary embolism in patients who have undergone hip replacement surgery

Please see full Prescribing Information, including boxed WARNING and Medication Guide.