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Dosing & Management
In this section:
- Information on starting your adult patients on PRADAXA Capsules, including a comprehensive dosing table
- Instructions on converting adult patients to PRADAXA Capsules
- General guidelines and information about assessing the anticoagulation activity of PRADAXA Capsules
- Information on discontinuing PRADAXA Capsules before surgery or other intervention
STARTING ADULT PATIENTS ON PRADAXA CAPSULES
Assess renal function prior to initiating treatment with PRADAXA Capsules1
Indication-specific dosage strengths available: 75 mg, 110 mg, and 150 mg Capsules
Dosing Information
![Glass Glass](/us/products/pradaxa/sites/default/files/2023-09/glass2.jpg)
Should be taken with a full glass of water1
![Plate Plate](/us/products/pradaxa/sites/default/files/2023-09/plate2.jpg)
Taken with or without food1
![INR INR](/us/products/pradaxa/sites/default/files/2023-09/INR2.jpg)
No INR monitoring required1
![clock clock](/us/products/pradaxa/sites/default/files/2023-09/clock.png)
Rapid onset-maximum plasma concentrations achieved 1-3 hours after administration1
![p450 p450](/us/products/pradaxa/sites/default/files/2023-09/p450.jpg)
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 adult 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 adult patients on PRADAXA
When converting adult patients to PRADAXA Capsules 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 CAPSULES: DOSING FOR MULTIPLE USES IN ADULT PATIENTS1
Recommended Dosing
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 Dailyfor 28-35 days |
Patients with CrCI >30 mL/min |
Dosing recommendation cannot be provided for adult patients with
- NVAF: CrCI <15 mL/min or on dialysis
- DVT/PE & HIP: CrCI ≤30 mL/min or on dialysis
Dosing With Concomitant Use of P-gp Inhibitors
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 Dailyfor 28-35 days |
Patients with CrCI ≥50 mL/min |
Avoid co-administration in adult patients with
- NVAF: CrCI <30 mL/min
- DVT/PE & HIP: CrCI <50 mL/min
![PDF Icon](/us/products/pradaxa/sites/default/files/2022-01/icon-pdf.jpg)
CONVERTING ADULT 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 CrCI 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 (e.g., intravenous unfractionated heparin) |
At the time of discontinuation |
Before initiating treatment with a parenteral anticoagulant:
Wait 12 hours after last dose of PRADAXA
CrCI ≥30 mL/min
Wait 24 hours after last dose of PRADAXA
CrCI <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
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 adult 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 adult 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 adult patients with various degrees of renal impairment*†
![Anticoagulant effect chart](/us/products/pradaxa/sites/default/files/2021-06/average-time.png)
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:
-
Pradaxa [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.
-
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.
Pradaxa® (dabigatran etexilate) Capsules is indicated:
- to reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation;
- for the treatment of deep venous thrombosis and pulmonary embolism in adult 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 adult patients who have been previously treated;
- for the prophylaxis of deep vein thrombosis and pulmonary embolism in adult patients who have undergone hip replacement surgery.
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;
history of a serious hypersensitivity reaction to dabigatran, dabigatran etexilate, or to one of the excipients of 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 Capsules is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant and restart PRADAXA Capsules 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 Capsules 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: In adults, a specific reversal agent (idarucizumab) for PRADAXA 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 all 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 in Adult Patients.
- For patients with moderate renal impairment (CrCl 30-50 mL/min), reduce the dose of PRADAXA Capsules to 75 mg twice daily when dronedarone or systemic ketoconazole is co-administered with PRADAXA.
- For patients with severe renal impairment (CrCl 15-30 mL/min), avoid concomitant use of PRADAXA Capsules and P-gp inhibitors.
Treatment and Reduction in the Risk of Recurrence of DVT/PE & Prophylaxis of DVT/PE Following Hip Replacement Surgery in Adult Patients.
For patients with CrCl <50 mL/min, avoid use of PRADAXA Capsules and concomitant P-gp inhibitors.
Increased Risk of Thrombosis in Patients with Triple-Positive Antiphospholipid Syndrome
There is an increased risk of thrombosis in patients with triple-positive antiphospholipid syndrome. PRADAXA use is not recommended.
ADVERSE REACTIONS
The most common adverse reactions (>15%) reported with PRADAXA are gastrointestinal adverse reactions and 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.
Females and Males of Reproductive Potential: Discuss pregnancy planning with females of reproductive potential requiring anticoagulation. Assess the risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, in females of reproductive potential and those with abnormal uterine bleeding.
Pediatric Use: The safety and effectiveness of PRADAXA Capsules for the treatment and the reduction in risk of recurrence of venous thromboembolism have been established in pediatric patients 8 to less than 18 years of age. Other age-appropriate pediatric dosage forms of dabigatran etexilate are available for pediatric patients less than 8 years of age for these indications. 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.
Geriatric: Risk of bleeding increases with age.
CL-PX-100063 06.28.2021
Please see full Prescribing Information, including boxed WARNING and Medication Guide.
- Boehringer Ingelheim
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