- ACRONYMS AND DEFINITIONS
- ACCP - American College of Chest Physicians
- AHA - American Heart Association
- A fib - Atrial fibrillation
- DVT - Deep vein thrombosis
- EF - Ejection fraction
- HR - Hazard ratio
- INR - International normalized ratio
- MI - Myocardial infarction
- NYHA - New York Heart Association heart failure classifications
- PCI - Percutaneous coronary intervention
- PE - Pulmonary embolism
- P-gp - P-glycoprotein
- PI - Manufacturer's package insert
- RCT - Randomized controlled trial
- TIA - Transient ischemic attack
- ULN - Upper limits of normal
- VTE - Venous thromboembolism (DVT and PE)
- DRUGS IN CLASS
- Direct Thrombin Inhibitors
- Dabigatran (Pradaxa®)
- MECHANISM OF ACTION
- Thrombin (Factor IIa)
- Thrombin activates platelets and facilitates the conversion of fibrinogen to fibrin. Fibrin cross-links to form a mesh where activated platelets are trapped. As platelets accumulate, a blood clot is formed. Direct thrombin inhibitors block the actions of thrombin on fibrinogen and platelets.
- FDA-APPROVED INDICATIONS
- Adults
- Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation
- Treatment of Deep Venous Thrombosis and Pulmonary Embolism - in patients who have been treated with a parenteral anticoagulant for 5 - 10 days
- Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism
- Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism Following Hip Replacement Surgery
- Pediatric (8 - 17 years old)
- Treatment of Venous Thromboembolic Events in Pediatric Patients
- Reduction in the Risk of Recurrence of Venous Thromboembolic Events in Pediatric Patients
- ATRIAL FIBRILLATION
- Overview
- Atrial fibrillation (A fib) is a common heart arrhythmia that increases a person's risk of stroke
- Dabigatran is approved for stroke prevention in nonvalvular atrial fibrillation which is atrial fibrillation that occurs in the absence of rheumatic mitral valve disease, a prosthetic heart valve, or mitral valve repair
- Dabigatran was compared to warfarin in the large trial detailed below
- The RE-LY study enrolled 18,113 patients with atrial fibrillation and other risk factors for stroke
Main inclusion criteria
- A fib and any one of the following: previous stroke or TIA, EF < 40%, NYHA class II - IV heart failure, age ≥ 75 years or age 65 - 74 with diabetes, hypertension, or coronary artery disease
Main exclusion criteria
- Severe heart valve disorder
- Stroke within 6 months
- High risk for bleeding
- CrCl < 30 ml/min
Baseline characteristics
- Average age 72 years
- Average CHADS2 score - 2.1
- Prior stroke or TIA - 20%
- A fib type: Persistent - 32% | Paroxysmal - 33% | Permanent - 35%
Randomized treatment groups
- Group 1 (6015 patients) - Dabigatran 110 mg twice a day
- Group 2 (6076 patients) - Dabigatran 150 mg twice a day
- Group 3 (6022 patients) - Warfarin (target INR 2.0 - 3.0)
- Warfarin therapy was open-label. Dabigatran was open-label but dose was blinded.
- Concomitant aspirin (< 100 mg/day) and other antiplatelet drugs were permitted
Primary outcome: Stroke or systemic embolism
Results
Duration: Median of 2 years | ||||
Outcome | Dab 110 | Dab 150 | Warfarin | Comparisons |
---|---|---|---|---|
Primary outcome (%/year) | 1.53% | 1.11% | 1.69% | 1 vs 3 p=0.34 | 2 vs 3 p<0.001 | 1 vs 2 p=0.005 |
Stroke (%/year) | 1.44% | 1.01% | 1.57% | 1 vs 3 p=0.41 | 2 vs 3 p<0.001 | 1 vs 2 p=0.003 |
Overall mortality (%/year) | 3.75% | 3.64% | 4.13% | 1 vs 3 p=0.13 | 2 vs 3 p=0.051 | 1 vs 2 p=0.66 |
Hemorrhagic stroke (%/year) | 0.12% | 0.10% | 0.38% | 1 vs 3 p<0.001 | 2 vs 3 p<0.001 | 1 vs 2 p=0.67 |
Major bleeding (%/year) | 2.71% | 3.11% | 3.36% | 1 vs 3 p=0.003 | 2 vs 3 p=0.31 | 1 vs 2 p=0.052 |
Dyspepsia | 11.8% | 11.3% | 5.8% | 1 and 2 vs 3 p<0.001 |
Drug discontinuation | 20.7% | 21.2% | 16.6% | 1 and 2 vs 3 p<0.001 |
|
Findings: In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those
associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and
systemic embolism but similar rates of major hemorrhage
- Professional guidelines:
- Summary
- Dabigatran is an effective alternative to warfarin in preventing stroke in atrial fibrillation
- In the right patients, it may confer a small, but significant benefit over warfarin
- Dabigatran is much more expensive than warfarin, but it does not require continuous monitoring and therapy adjustments that are common with warfarin
- VTE TREATMENT
- Overview
- Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism
- Dabigatran is approved for the treatment of VTE after 5 - 10 days of initial parenteral anticoagulation
- Dabigatran was compared to warfarin for the treatment of VTE in the RE-COVER study detailed below
- The RE-COVER study enrolled 2539 patients with acute venous thromboembolism (DVT or PE)
Main inclusion criteria
- Acute, symptomatic, objectively verified proximal DVT or PE
Main exclusion criteria
- Duration of symptoms > 14 days
- Hemodynamic instability
- High risk for bleeding
- CrCl < 30 ml/min
Baseline characteristics
- Average age 55 years
- Previous VTE - 26%
- Active cancer - 4.7%
- Qualifying event: DVT - 69% | PE - 21% | Both - 9.6%
Randomized treatment groups
- Group 1 (1274 patients) - Dabigatran 150 mg twice a day for 6 months
- Group 2 (1265 patients) - Warfarin (target INR 2.0 - 3.0) for 6 months
- All patients were given parenteral anticoagulation for at least 5 days
- Warfarin was started at randomization and parenteral anticoagulation was continued until the INR was at least 2.0
- Dabigatran was started when parenteral anticoagulation was stopped. The first dose was given within 2 hours of the time that the next dose of parenteral therapy would have been due.
- Parenteral anticoagulation was given for an average of 10 days in both groups
Primary outcome: Composite of symptomatic venous thromboembolism or death associated with venous thromboembolism in the
6 months after random assignment
Results
Duration: 6 months | |||
Outcome | Dabigatran | Warfarin | Comparisons |
---|---|---|---|
Primary outcome | 2.4% | 2.1% | HR 1.10, 95%CI [0.65 - 1.84] |
Symptomatic DVT | 1.3% | 1.4% | HR 0.87, 95%CI [0.44 - 1.71] |
Symptomatic nonfatal PE | 1.0% | 0.6% | HR 1.85, 95%CI [0.74 - 4.64] |
Overall mortality | 1.6% | 1.7% | HR 0.98, 95%CI [0.53 - 1.79] |
Major bleeding | 1.6% | 1.9% | HR 0.82, 95%CI [0.45 - 1.48] |
Major or clinically relevant nonmajor bleeding | 5.6% | 8.8% | HR 0.63, 95%CI [0.47 - 0.84] |
Early drug discontinuation | 16% | 14.5% | N/A |
|
Findings: For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar
to that of warfarin, and does not require laboratory monitoring
- Professional recommendations
- Summary
- Dabigatran is effective in treating VTE. Dabigatran is only approved after 5 - 10 days of parenteral anticoagulation. This puts it at a disadvantage when compared to certain Factor Xa inhibitors which do not require initial parenteral anticoagulation.
- VTE PREVENTION
- Overview
- Dabigatran is approved for the prevention of recurrent DVT and PE in patients who have experienced a previous episode
- Dabigatran was compared to warfarin for the extended treatment of VTE in the RE-MEDY study detailed below
- The RE-MEDY study enrolled 2856 patients who had been treated for 3 - 12 months with anticoagulation for a VTE
Main inclusion criteria
- Symptomatic, objectively confirmed DVT or PE that had been treated for 3 - 12 months with approved anticoagulation
- Increased risk for recurrent VTE based on site investigator's assessment
Main exclusion criteria
- Interruption of anticoagulant therapy for ≥ 2 weeks during the initial 3 - 6 months
- High risk for bleeding
- CrCl < 30 ml/min
- Significant liver disease
Baseline characteristics
- Average age 55 years
- Active cancer - 4%
- Known thrombophilia - 18%
- Qualifying event: DVT - 65% | PE - 23% | Both - 12%
Randomized treatment groups
- Group 1 (1430 patients) - Dabigatran 150 mg twice a day
- Group 2 (1426 patients) - Warfarin (target INR 2 - 3)
- Average treatment before study enrollment was 199 days
Primary outcome: Composite of recurrent symptomatic and objectively verified venous thromboembolism or death associated
with venous thromboembolism
Results
Duration: Average of 473 days | |||
Outcome | Dabigatran | Warfarin | Comparisons |
---|---|---|---|
Primary outcome | 1.8% | 1.3% | HR 1.44, 95%CI [0.78 - 2.64] |
Symptomatic DVT | 1.2% | 0.9% | HR 1.32, 95%CI [0.64 - 2.71], p=0.46 |
Symptomatic nonfatal PE | 0.7% | 0.4% | HR 2.04, 95%CI [0.70 - 5.98], p=0.19 |
Overall mortality | 1.2% | 1.3% | HR 0.90, 95%CI [0.47 - 1.72], p=0.74 |
Major bleeding | 0.9% | 1.8% | HR 0.52, 95%CI [0.27 - 1.02], p=0.06 |
Major or clinically relevant bleeding | 5.6% | 10.2% | HR 0.54, 95%CI [0.41 - 0.71], p<0.001 |
Acute coronary syndrome | 0.9% | 0.2% | p=0.02 |
Findings: Dabigatran was effective in the extended treatment of venous thromboembolism and carried a lower risk of major or clinically relevant bleeding
than warfarin but a higher risk than placebo
- Professional recommendations
- HIP REPLACEMENT
- Overview
- Patients undergoing hip replacement surgery are at a high risk of VTE for an extended period of time following surgery
- One large study compared dabigatran to enoxaparin for VTE prevention after hip surgery
- The RE-NOVATE study enrolled 3494 patients undergoing total hip replacement
Main inclusion criteria
- Scheduled to undergo unilateral total hip replacement
Main exclusion criteria
- Bleeding disorder
- History of acute intracranial disease or hemorrhagic stroke
- GI bleed or ulcer disease within 6 months
- Use of long-acting NSAIDs
- Significant liver disease
- CrCl < 30 ml/min
Baseline characteristics
- Average age 64 years
- History of VTE - 3%
- Average duration of surgery - 86 minutes
- Median duration of hospital stay - 9 days
Randomized treatment groups
- Group 1 (1146 patients) - Dabigatran 220 mg once daily for 28 - 35 days
- Group 2 (1163 patients) - Dabigatran 150 mg once daily for 28 - 35 days
- Group 3 (1154 patients) - Enoxaparin 40 mg subq daily for 28 - 35 days
- Enoxaparin was started the evening before surgery
- Dabigatran was started 1 - 4 hours after surgery. First dose was halved.
- Compression stockings were permitted, but intermittent pneumatic compression devices were not.
Primary outcome: Composite of symptomatic thromboembolism (DVT and PE), thromboembolism detected on venography performed
within 24 hours of last dose, and death from any cause
Results
Duration: Median of 33 days | ||||
Outcome | Dab 220 | Dab 150 | Enoxaparin | Comparisons |
---|---|---|---|---|
Primary outcome | 6% | 8.6% | 6.7% | 1 vs 3 p>0.05 | 2 vs 3 p>0.05 |
Major bleeding | 2% | 1.3% | 1.6% | 1 vs 3, p=0.44, 2 vs 3, p=0.60 |
Asymptomatic DVT | 4.6% | 7.2% | 6.3% | N/A |
Symptomatic PE | 0.4% | 0.1% | 0.3% | N/A |
Overall mortality | 0.3% | 0.3% | 0% | N/A |
|
Findings: Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery,
with a similar safety profile
- Professional recommendations
- The ACCP guidelines from 2012 state that low molecular weight heparins (e.g. enoxaparin) are the preferred agents for thromboembolism prophylaxis after major orthopedic surgeries
- Dabigatran, apixaban, and rivaroxaban are acceptable alternatives for patients unwilling to inject themselves daily with low molecular weight heparins, but they lack long-term safety data [9]
- SIDE EFFECTS
- Bleeding
- The therapeutic effect of dabigatran is to inhibit clot formation, therefore it will inherently increase the risk of unwanted bleeding
- In the RE-LY study, the risk of major bleeding was not different from warfarin for the 150 mg dose. The 110 mg dose had significantly less bleeding.
- See reversing dabigatran below for a review stopping bleeding in emergency situations
- Upset stomach (dyspepsia)
- In some studies, the incidence of dyspepsia was higher in dabigatran-treated patients than in warfarin-treated patients. In the RE-LY study detailed above, 12% of patients treated with dabigatran complained of dyspepsia compared to 5.8% of patients treated with warfarin.
- COAGULATION STUDY EFFECTS
- Dilute thrombin time (dTT)
- The dTT is a clotting assay that correlates closely with dabigatran levels. It is one of the preferred tests for measuring dabigatran activity.
- Unfortunately, the dTT is not widely available.
- Ecarin clotting time (ECT) and ecarin chromogenic assay (ECA)
- The ECT and ECA are clotting assays that correlate closely with dabigatran levels. They are preferred tests for measuring dabigatran activity.
- These tests may not be widely available, especially in emergency situations. [4,5,16]
- Thrombin time (TT)
- Dabigatran prolongs the thrombin time, but the effect is nonlinear
- A normal TT typically excludes clinically relevant dabigatran levels, but a prolonged TT does not discriminate between clinically important and insignificant levels [16]
- Partial thromboplastin time (aPTT)
- Dabigatran prolongs the aPTT, but the effect is nonlinear
- A normal aPTT typically excludes clinically relevant dabigatran levels if a sensitive reagent is used
- A prolonged aPTT does not discriminate between clinically important and insignificant levels [16]
- Prothrombin time (PT) and INR
- Dabigatran may prolong the PT and INR
- The effect is linear, but small
- The PT/INR is not a sensitive measure of the effect of dabigatran [4,5]
- CONTRAINDICATIONS
- Active pathological bleeding
- History of a serious hypersensitivity reaction to dabigatran, dabigatran etexilate, or to one of the excipients of the product (e.g. anaphylactic reaction or anaphylactic shock)
- Mechanical prosthetic heart valve
- Kidney disease with certain medications - See drug interactions below
- PRECAUTIONS
- Kidney disease
- Adults: kidney disease dosing recommendations are incorporated into the standard dosing recommendations. See dosing below for more.
- Pediatric: dabigatran has not been studied in pediatric patients with GFR < 50 ml/min, and it is not recommended in these patients
- Liver disease
- Dabigatran is not metabolized by the Cytochrome P450 system
- The manufacturer makes no specific dosage recommendations in liver disease
- Patients with severe liver disease often have blood clotting disorders (see coagulopathy of liver disease). Use with caution in these patients [5]
- Prosthetic heart valve
- Dabigatran should not be used in patients with mechanical prosthetic heart valves. The RE-ALIGN study compared dabigatran to warfarin in patients with mechanical heart valves. The study was stopped after 252 patients were enrolled because the dabigatran group had a significantly higher incidence of stroke and major bleeding. [PMID 23991661]
- See bioprosthetic heart valves and transcatheter aortic valve replacement for antithrombotic recommendations in other types of heart valves.
- Body weight
- A case report in the NEJM found that body weight may affect blood levels of dabigatran [PMID 23782198]
- In the case report, the authors note that in the RE-LY study, trough levels of dabigatran in patients who weighed more than 220 pounds were 20% lower than trough levels in patients who weighed 110 - 220 pounds
- The package insert for dabigatran does not discuss the possible effects of body weight on dabigatran
- Physicians should be aware that dabigatran efficacy may be decreased in obese patients. Further studies of the effects of body weight on dabigatran pharmacokinetics are needed.
- Antiphospholipid antibody (APA) syndrome
- Antiphospholipid antibody syndrome is an autoimmune syndrome that increases a person's risk for thrombosis. Patients with APA syndrome who are triple positive (positive for lupus anticoagulant, anticardiolipin, and anti-beta 2-glycoprotein I antibodies) are at greatest risk for thrombosis.
- A small study that compared rivaroxaban to warfarin in patients with triple-positive APA syndrome was stopped early when rivaroxaban was found to be clearly inferior to warfarin for preventing thromboembolic events. [PMID 30002145] Another study that compared rivaroxaban to warfarin for preventing recurrent thrombosis in patients with APA syndrome did not prove that rivaroxaban was noninferior to warfarin. [PMID 31610549] If this study had more power, it's likely rivaroxaban would have been inferior.
- After rivaroxaban was found to be inferior to warfarin in APA syndrome, the prescribing information for dabigatran was updated to include a warning against its use in APA syndrome
- REVERSING DABIGATRAN
- Idarucizumab
- In emergency situations, the effects of dabigatran may need to be reversed immediately
- An antibody fragment specific for dabigatran called idarucizumab has been developed. Idarucizumab binds dabigatran and inactivates it.
- In 2015, a study published in the NEJM found that idarucizumab completely reversed the anticoagulant effects of dabigatran within minutes in 88 - 98% of patients [PMID 26095746]. A phase 1 study published in the Lancet also found idarucizumab to be effect in reversing dabigatran [PMID 26088268]. A cohort study published in 2017 found idarucizumab to be effective in clinical practice [PMID 28693366].
- In 2015, the FDA approved idarucizumab (Praxbind®) for emergency reversal of dabigatran in adults. It has not been studied in pediatric patients.
- As far as using blood products to reverse dabigatran, prothrombin complex concentrate has been studied in one trial, and it had no effect [PMID 21900088]
- Professional recommendations
- Two professional organizations have issued guidelines on reversing dabigatran. Links to both guidelines are available below.
- STOPPING BEFORE PROCEDURES
- Professional recommendations
- Manufacturer recommendations
- CrCl ≥ 50 ml/min: discontinue 1 - 2 days before invasive or surgical procedures
- CrCl < 50 ml/min: discontinue 3 - 5 days before invasive or surgical procedures
- 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
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- Dabigatran
- Drugs that increase the risk of bleeding - drugs that inhibit coagulation may increase the risk of bleeding when taken with direct thrombin inhibitors
- Drugs that may increase the risk of bleeding include:
- P-glycoprotein (P-gp) inducers/inhibitors - dabigatran is a sensitive P-glycoprotein substrate. Recommendations for concomitant use of P-glycoprotein inhibitors/inducers with dabigatran depend on the indication, the patient's kidney function, and the specific drug. The recommendations given below for specific P-gp inhibitors should not be extrapolated to other P-gp inhibitors. The combination of P-gp inhibitors and dabigatran in pediatric patients has not been studied, and caution should be used when treating this population.
- Atrial fibrillation
- P-gp inducers: DO NOT COMBINE
- P-gp inhibitors and CrCl < 30 ml/min: DO NOT COMBINE
- P-gp inhibitors dronedarone or systemic ketoconazole and CrCl 30 - 50 ml/min: reduce dose of dabigatran to 75 mg twice daily
- P-gp inhibitors verapamil, amiodarone, quinidine, clarithromycin, and ticagrelor and CrCl 30 - 50 ml/min: no dose adjustment necessary
- Treatment and prevention of recurrent VTE
- P-gp inducers: DO NOT COMBINE
- P-gp inhibitors and CrCl < 50 ml/min: DO NOT COMBINE
- VTE prophylaxis after hip surgery
- P-gp inducers: DO NOT COMBINE
- P-gp inhibitors and CrCl < 50 ml/min: DO NOT COMBINE
- P-gp inhibitors dronedarone or systemic ketoconazole and CrCl ≥ 50 ml/min: give dabigatran several hours before or after P-gp inhibitor
- Metabolism and clearance
- P-glycoprotein - substrate
- Dabigatran undergoes glucuronidation
- Dabigatran does not undergo Cytochrome P450 metabolism
- DOSING
- Dosage form (capsule)
- 75 mg
- 110 mg
- 150 mg
- Comes in blister package or bottle with 60 capsules
- Generic available for 75 mg and 150 mg doses. Costs > $150 for 60 capsules.
Recommended dosing in adults |
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Nonvalvular atrial fibrillation
|
Treatment of DVT and PE
|
Prevention of recurrent DVT and PE
|
VTE prophylaxis after hip replacement
|
- Missed doses
- If a dose 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. Do not double the dose to make up for a missed dose.
- Switching between warfarin and parenteral anticoagulants
- From warfarin to dabigatran - discontinue warfarin and start dabigatran when the INR is below 2.0
- From dabigatran to warfarin
- CrCl ≥ 50 mL/min: start warfarin 3 days before discontinuing dabigatran
- CrCl 30 - 50 mL/min: start warfarin 2 days before discontinuing dabigatran
- CrCl 15 - 30 mL/min: start warfarin 1 days before discontinuing dabigatran
- CrCl < 15 mL/min: no recommendation can be made
- Parenteral anticoagulant to dabigatran - For patients currently receiving a parenteral anticoagulant, start dabigatran 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)
- Dabigatran to parenteral anticoagulant
- CrCl ≥ 30 ml/min: wait 12 hours after the last dose of dabigatran before initiating treatment with a parenteral anticoagulant
- CrCl < 30 ml/min: wait 24 hours after the last dose of dabigatran before initiating treatment with a parenteral anticoagulant
- Pediatric dosing (8 - 17 years)
- For the treatment of VTE in pediatric patients, initiate therapy following treatment with a parenteral anticoagulant for at least 5 days
- For reduction in risk of recurrence of VTE, initiate therapy following previous treatment
- Dosing is based on body weight as shown in the table below
- May take without regard to food. Swallow capsule whole with full glass of water.
Dabigatran Dosing in Pediatric Patients (8 - 17 years) | ||
---|---|---|
Actual Weight | Dose | # of capsules |
24.2 lbs (11 kg) to less than 35.2 lbs (16 kg) | 75 mg twice daily | one 75 mg capsule twice daily |
35.2 lbs (16 kg) to less than 57.2 lbs (26 kg) | 110 mg twice daily | one 110 mg capsule twice daily |
57.2 lbs (26 kg) to less than 90.2 lbs (41 kg) | 150 mg twice daily | one 150 mg capsule twice daily or two 75 mg capsules twice daily |
90.2 lbs (41 kg) to less than 134.2 lbs (61 kg) | 185 mg twice daily | one 110 mg capsule plus one 75 mg capsule twice daily |
134.2 lbs (61 kg) to less than 178.2 lbs (81 kg) | 220 mg twice daily | two 110 mg capsule twice daily |
≥ 178.2 lbs (81 kg) | 260 mg twice daily | one 150 mg capsule plus one 110 mg capsule twice daily or one 110 mg capsule plus two 75 mg capsules twice daily |
- Storage
- Dabigatran comes in bottles and blister packages
- Dabigatran is sensitive to moisture which can cause breakdown of the active ingredient
- Pharmacies should dispense dabigatran in its original bottle or blister package and not repackage it
- Patients should leave dabigatran in its original bottle or blister package and not place it in pill boxes, etc.
- Capsules should remain in blister packages until they are used. Once a bottle is opened, capsules are good for 4 months.
- LONG TERM SAFETY
- Dabigatran was approved for use in the U.S. in October 2010
- It has been studied in a number of large trials and appears to be safe when prescribed appropriately
- BIBLIOGRAPHY
- 1 - 16908781
- 2 - 19717844 - RE-LY study
- 3 - 22858728 - AHA statement on Afib
- 4 - 17506785 - Clotting study
- 5 - Dabigatran PI
- 6 - 21900088
- 7 - 19966341 - RE-COVER study
- 8 - 21422387 - AHA GL on VTE
- 9 - 22315278 - ACCP GL on VTE
- 10 - 17869635 - RE-NOVATE study
- 11 - 23425163 - RE-MEDY AND RE-SONATE
- 12 - 24682348 - AHA 2014 A fib GL
- 13 - 26867832 - ACCP 2016 VTE update
- 14 - 23625942 - European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation
- 15 - 23147769 - Periprocedural Management and Approach to Bleeding in Patients Taking Dabigatran
- 16 - 29203195 - 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants