1. Marion General Hospital Formulary Evaluation
Monograph
Generic Name (Trade Name): Dabigatran (Pradaxa)
Manufacturer: Boehringer-Ingelheim
Dosage Forms (NDC #): oral tablet
AHFS Class: Anticoagulant
Storage: 25°C, store in original package to protect from moisture, once opened use within 4 months.
Description and Pharmacology: Dabigatran is an anticoagulant that directly inhibits thrombin to prevent the formation of a
clot.
Pharmacokinetics
• See supplementary handout
FDA-Approved Indications1
• Reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. (1.1)
• Treatment of DVT and PE
• Reduction in risk of recurrent DVT/PE following initial therapy
Clinical Trials
Title Randomized Evaluation of Long-term Anticoagulant Therapy (RE-LY)
Objective Compare efficacy and safety of dabigatran with warfarin in patients with non-
valvular A.fib.
Design Multi-center, multi-national randomized double blind study
18,113 patients
Follow up: 2 years
Methods Treatment arms: Dabigatran 110mg BID and 150mg BID vs. Warfarin dosed to
target INR of 2-3
1°: Composite of stroke and systemic embolism
1° safety outcome: major bleeding
Results Dabigatran 110mgBID vs. 150mg BID vs. warfarin
Rate of stroke or systemic embolism (annual event rate): 1.5%( p=0.34) vs. 1.1%
(p<0.001) vs. 1.7%
Major bleeding (annual event rate): 2.7%(p=0.003) vs. 3.1% (p=0.31)vs. 3.4%
Conclusions Both Dabigatran strengths showed reduce rate of stroke or systemic embolism when
compared to warfarin. Dabigatran dosed 150mg BID was the only one to show
statistical significance. Both doses of Dabigatran showed less intra-cerebral,
lifethreatening and total bleeding compared to warfarin. Dabigatran showed no
difference in major bleeding with 150mg strength but did with 110mg strength.
Comments
Title Treatment and Reduction in the Risk of Recurrence of DVT and PE (RE-
COVER and RE-COVER II)
Objective Compare efficacy and safety of dabigatran vs. warfarin for the treatment of acute
VTE with an added goal to confirm the results in RE-COVER 1 with results from RE-
COVER II
Design Randomized, double blind phase III non-inferiority trial
2539 patients: RE-COVER I

2. 2568 patients: RE-COVER II
Methods Treatment arms: Dabigatran 150mg BID after initial treatment with LMWH or UFH
vs. warfarin dosed to a target INR of 2-3 after > 5 days of parenteral anticoagulation
Primary outcomes: VTE and VTE related death
Safety outcome: Major bleeding
Results Dabigatran vs. Warfarin
RE-COVER I:
• Symptomatic VTE and VTE related deaths: 30/1274 pts (2.4%) vs.
27/1265pts (1.9%) p<0.001
• Major bleeding: 20/1274 pts (1.6%) vs. 24/1265 pts(1.9%)
• Major or clinically relevant non-major bleeding: 71pts (5.6%) vs. 111pts
(8.8%), p=0.002, Relative Risk Reduction: 37%
RE-COVER II:
• Recurrent VTE and VTE-related death: 30/1279 pts (2.3%) vs. 28/1289 pts
(2.2%) HR: 1.08 p<0.001
• Major bleeding 15pts (1.2%) vs. 22pts (1.7%) HR: 0.69
• Rates of any bleeding: 200 events (15.6%) vs. 285 events (22.1%), Relative
Risk Reduction: 33%
Conclusions Dabigatran demonstrated non-inferiority to warfarin in the patients with acute VTE in
the prevention of recurrent or fatal VTE. Dabigatran also demonstrated lower risk of
bleeding.
Comments
Safety and Tolerability
Contraindications: Active pathological bleeding, hypersensitivity reaction to Dabigatran, mechanical prosthetic heart
valve
Warnings and Precautions:
• Can cause serious and fatal bleeding
• Use in patients with bioprosthetic heart valves is not recommended
.
Adverse Drug Effects
• See supplementary handout
Drug Interactions
• P-gp inducers: Avoid co-administration
• P-gp inhibitors:
o Dronedarone or ketoconazole: reduce dose if CrCl 30-50mL/min
o Verapamil, amiodarone,quinidine, clarithromycin, and ticagrelor: no dose adjustment
o Patients with CrCl <30 mL/min: Not recommended
Medication Error Possibility
• None identified

3. Dosing and Administration
• See supplementary handout.
References
1. Dabigatran [Package Insert]. Ridgefield: Boehringer Ingelheim Pharmaceuticals, Inc; 2015.
2. RE-LY. Anticoagulation-trials website: http://www.anticoagulant-trials.eu/studies-a-z/detail/study/re-ly.html. March
2015. Accessed April 21, 2015.