IMPORTANT SAFETY INFORMATION
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 to PRADAXA (e.g., anaphylactic reaction or anaphylactic shock);
- 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).
USE IN SPECIFIC POPULATIONS
- Pregnancy: The limited available data on PRADAXA use
in pregnant women are insufficient to determine drug-associated risks for
adverse developmental outcomes.
- Lactation: Breastfeeding is not recommended.
- Geriatric: Risk of bleeding increases with age.
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