Starting patients on PRADAXA

Assess renal function prior to initiating treatment with PRADAXA1

Indication-specific dosage stengths available: 75 mg, 110 mg, and 150 mg

Dosing Information

  • Should be taken with a full glass of water
    Should be taken with a full class of water1
  • Taken with or without food
    Taken with or without food1
  • No INR monitoring required
    No INR monitoring required1
  • Taken with or without food
    Rapid onset—maximum plasma concentrations achieved 1-3 hours after administration1
  • P450
    Not metabolized by the cytochrome P450 system1
Periodically assess renal function as clinically indicated and adjust therapy accordingly1
  • Assess more frequently in clinical situations that may be associated with a decline in renal function
  • Discontinue PRADAXA in patients who develop acute renal failure and consider alternative anticoagulant therapy
  • Generally, the extent of anticoagulation does not need to be assessed. When necessary, use aPTT and not INR to assess for anticoagulant activity in patients on PRADAXA
When converting patients to PRADAXA from:
  • Warfarin: Discontinue warfarin and start PRADAXA when INR is <2.01
  • Parenteral anticoagulants: 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 (eg, intravenous unfractionated heparin)1

PRADAXA: Dosing for multiple uses1

Reduce Stroke
Risk in NVAF
150 mg
Twice Daily
Patients with
CrCI >30 mL/min
75 mg
Twice Daily
Patients with
CrCI 15-30 mL/min
Treat DVT & PE or
Reduce Risk
of Recurrence
150 mg
Twice Daily
For treatment only: Initial
treatment with parenteral
anticoagulant for 5-10 days
Patients with
CrCI >30 mL/min
Reduce DVT & PE
Risk After Hip
Replacement Surgery
110 mg
1-4 hours post-surgery and after
achieving hemostasis, then
220 mg Once Daily
for 28-35 days
Patients with
CrCI >30 mL/min
Dosing recommendation cannot be provided for patients with
  • NVAF: CrCl <15 mL/min or on dialysis
  • DVT/PE & HIP: CrCl ≤30 mL/min or on dialysis
Reduce Stroke
Risk in NVAF
150 mg
Twice Daily
Patients with
CrCI >50 mL/min
75 mg
Twice Daily
Patients with
CrCI 30-50 mL/min
with dronedarone or
systemic ketoconazole
Treat DVT & PE or
Reduce Risk
of Recurrence
150 mg
Twice Daily
For treatment only: Initial
treatment with parenteral
anticoagulant for 5-10 days
Patients with
CrCI ≥50 mL/min
Reduce DVT & PE
Risk After Hip
Replacement Surgery
110 mg
1-4 hours post-surgery and after
achieving hemostasis, then
220 mg Once Daily
for 28-35 days
Patients with
CrCI ≥50 mL/min
Avoid co-administration in patients with
  • NVAF: CrCl <30 mL/min
  • DVT/PE & HIP: CrCl <50 mL/min
Download the full PRADAXA dosing guide here

Converting patients on pradaxa to and from other anticoagulants

Discontinue warfarin
&
Start PRADAXA
when the INR is <2.0

Adjust the starting time of warfarin based on CrCl as follows:

Recommended start of warfarin before discontinuing PRADAXA Creatinine clearance
3 days ≥50 mL/min
2 days 30-50 mL/min
1 day 15-30 mL/min
No recommendations can be made <15 mL/min

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

Administration of parental anticoagulant Recommended starting time of PRADAXA
Scheduled dosing 0 to 2 hours before time of next dose
Continuous infusion
(eg. intravenous unfractionated heparin)
At the time of discontinuation

Before initiating treatment with a parenteral anticoagulant:

Wait 12 hours after last dose of PRADAXA
Wait 24 hours after last dose of PRADAXA
CrCl ≥30 mL/min
CrCl <30 mL/min

Discontinuing Pradaxa for Surgery and Other Interventions1

Half-life
  • Healthy subjects: 12-17 hours
Before invasive or surgical procedures
  • Due to an increased risk of bleeding, PRADAXA should be discontinued before invasive or surgical procedures, if possible:
Discontinue 1-2 days before procedure
Discontinue 3-5 days before procedure
CrCl ≥50 mL/min
CrCl <50 mL/min

Consider longer times for patients undergoing major surgery, spinal puncture, or placement of a spinal epidural catheter or port, in whom complete hemostasis may be required

Additional Guidance
Risk of bleeding1
  • 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 the specific reversal agent Praxbind® (idarucizumab) in case of emergency surgery or urgent procedures when reversal of the anticoagulant effect of dabigatran is needed
    • Refer to the prescribing information for PRAXBIND for additional information
    • Restart PRADAXA as soon as medically appropriate.
Discontinuation and increased risk of thrombotic events1
  • 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, consider coverage with another anticoagulant and restart PRADAXA as soon as medically appropriate

Assessing anticoagulation activity of PRADAXA

General guidelines for assessment
  • INR is relatively insensitive to the exposure to dabigatran and cannot be interpreted the same way as used for warfarin monitoring1
  • When assessment is necessary, use aPTT and not INR to assess for anticoagulant activity in patients on PRADAXA1
    • PRADAXA prolongs aPTT at therapeutic doses1
  • When possible, determine time of last dose of PRADAXA relative to time of blood sampling2
Anticoagulant effect
  • aPTT provides an approximation of anticoagulant effect1
    • Prolongation of aPTT occurs with increasing PRADAXA plasma concentration2
    • In the RE‑LY® Trial, median (10th to 90th percentile) trough aPTT in patients receiving the PRADAXA 150-mg dose was 52 (40 to 76) seconds1
  • The degree of anticoagulant activity can also be assessed by the ECT. This test is a more specific measure of the effect of dabigatran than aPTT1

Average time course for effects of dabigatran on aPTT in patients with various degrees of renal impairment*

Anticoagulant effect chart
  • While advice cannot be provided on the level of recovery of aPTT needed in any particular clinical setting, curves in the aPTT time course can be used to estimate time to reach a particular level of aPTT recovery—even when time since the last dose of PRADAXA is not precisely known1
    • Plasma concentration levels decline relatively quickly following discontinuation in patients with normal renal function2
aPTT = activated partial thromboplastin time
INR = international normalized ratio
P-gp = P-glycoprotein
*
Curves represent mean levels without confidence intervals; variations should be expected when measuring aPTT.1
Simulations based on PK data from a study in subjects with renal impairment and PK/aPTT relationships derived from the RE‑LY® Trial; aPTT prolongation in RE‑LY® was measured centrally in citrate plasma using PTT Reagent (Roche Diagnostics GmbH, Mannheim, Germany). There may be quantitative differences between various established methods for aPTT assessment.1
References: 1. Pradaxa [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 2. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116-1127.

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

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;

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.

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;

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).