CLINICAL PHARMACOLOGY Mechanism of Action:
Dabigatran and its acyl glucuronides are competitive, direct thrombin
inhibitors. Because thrombin (serine protease) enables the conversion of
fibrinogen into fibrin during the coagulation cascade, its inhibition prevents
the development of a thrombus. Both free and clot-bound thrombin, and
thrombin-induced platelet aggregation are inhibited by the active moieties.
INDICATIONS AND USAGE
PRADAXA is indicated to reduce the risk of stroke and systemic embolism in
patients with non-valvular atrial fibrillation.
DOSAGE AND ADMINISTRATION Recommended Dose:
For patients with creatinine clearance (CrCl) >30 mL/min, the recommended dose
of PRADAXA is 150 mg taken orally, twice daily, with or without food. For
patients with CrCl 15-30 mL/min, the recommended dose is 75 mg twice daily.
Dosing recommendations for patients with a CrCL <15 mL/min or on dialysis cannot
Instruct patients to swallow the capsules whole. Breaking, chewing, or emptying
the contents of the capsule can result in increased exposure. 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.
---------- Converting from or to Warfarin:
When converting patients from warfarin therapy to PRADAXA, discontinue warfarin
and start PRADAXA when the international normalized ratio (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
For CrCl 31-50 mL/min, start warfarin 2 days before
For CrCl 15-30 mL/min, start warfarin 1 day before
For CrCl <15 mL/min, no recommendations can be made.
Because PRADAXA can contribute to an elevated INR, the INR will better reflect
warfarin’s effect after PRADAXA has been stopped for at least 2 days.
---------- 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
---------- Surgery and 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.
If surgery cannot be delayed, there is an increased risk of bleeding. This risk
of bleeding should be weighed against the urgency of intervention. Bleeding risk
can be assessed by the ecarin clotting time (ECT). This test is a better marker
of the anticoagulant activity of dabigatran than activated partial
thromboplastin time (aPTT), prothrombin time (PT)/INR, or thrombin time (TT). If
ECT is not available, the aPTT test provides an approximation of PRADAXA’s
See dosage information above.
No dose adjustment of PRADAXA is recommended in patients with mild or
moderate renal impairment. Reduce the dose of PRADAXA in patients with
severe renal impairment (CrCl 15-30 mL/min). Dosing recommendations for
patients with CrCl <15 mL/min or on dialysis cannot be provided.
Dosing recommendations for patients with CrCl <15 mL/min or on
dialysis cannot be provided.
National Institutes of Health, U.S. National Library of Medicine,
DailyMed Database. Provides access to the latest drug monographs submitted to the
Food and Drug Administration (FDA). Please review the latest applicable package insert for
additional information and possible updates. A local search
option of this data can be found here.
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical
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