Complete adverse effect profile including incidence rates and management
Important Safety Information
This is not a complete list of all possible side effects. Contact your healthcare provider if you experience any unexpected symptoms. For serious or life-threatening side effects, seek emergency medical attention immediately.
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Increased Risk of Thrombotic Events after Premature Discontinuation [see Warnings and Precautions (5.1)] Risk of Bleeding [see Warnings and Precautions (5.2)] Spinal/Epidural Anesthesia or Puncture [see Warnings and Precautions (5.3)] Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves [see Warnings and Precautions (5.4)] Increased Risk of Thrombosis in Patients with Triple-Positive Antiphospholipid Syndrome [see Warnings and Precautions (5.6)] The most serious adverse reactions reported with dabigatran etexilate were related to bleeding [see Warnings and Precautions (5.2)].
Most common adverse reactions (>15%) are gastrointestinal adverse reactions and bleeding ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adult Trials Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation The RE-LY (Randomized Evaluation of Long-term Anticoagulant Therapy) study provided safety information on the use of two doses of dabigatran etexilate capsules and warfarin [see Clinical Studies (14.1)] .
The numbers of patients and their exposures are described in Table
Limited information is presented on the 110 mg dosing arm because this dose is not approved.
Table 2: Summary of Treatment Exposure in RE-LY Dabigatran Etexilate Capsules 110 mg twice daily Dabigatran Etexilate Capsules 150 mg twice daily Warfarin Total number treated 5,983 6,059 5,998 Exposure > 12 months 4,936 4,939 5,193 > 24 months 2,387 2,405 2,470 Mean exposure (months) 20.5 20.3 21.3 Total patient-years 10,242 10,261 10,659 Drug Discontinuation in RE-LY The rates of adverse reactions leading to treatment discontinuation were 21% for dabigatran etexilate capsules 150 mg and 16% for warfarin.
The most frequent adverse reactions leading to discontinuation of dabigatran etexilate capsules were bleeding and gastrointestinal events (i.e., dyspepsia, nausea, upper abdominal pain, gastrointestinal hemorrhage, and diarrhea).
Bleeding [see Warnings and Precautions (5.2)] Table 3 shows the number of adjudicated major bleeding events during the treatment period in the RE-LY study, with the bleeding rate per 100 subject-years (%).
Major bleeding is defined as bleeding accompanied by one or more of the following: a decrease in hemoglobin of ≥2 g/dL, a transfusion of ≥2 units of packed red blood cells, bleeding at a critical site or with a fatal outcome.
5 WARNINGS AND PRECAUTIONS Bleeding: Dabigatran etexilate can cause serious and fatal bleeding ( 5.2 ) Bioprosthetic heart valves: Dabigatran etexilate use not recommended ( 5.4 ) Increased Risk of Thrombosis in Patients with Triple-Positive Antiphospholipid Syndrome: Dabigatran etexilate use not recommended ( 5.6 ) 5.1 Increased Risk of Thrombotic Events after Premature Discontinuation Premature discontinuation of any oral anticoagulant, including dabigatran etexilate, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events.
If dabigatran etexilate capsules are discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant and restart dabigatran etexilate capsules as soon as medically appropriate [see Dosage and Administration (2.6, 2.7, 2.8)].
5.2 Risk of Bleeding Dabigatran etexilate 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 dabigatran etexilate capsules in patients with active pathological bleeding [see Dosage and Administration (2.4)].
Like all medications, Dabigatran Etexilate can cause side effects. However, not everyone who takes this medication will experience them. Many side effects are dose-dependent and may improve as your body adjusts to the medication. Others may require dose adjustment or medical attention.
Contact your healthcare provider promptly if you experience:
Seek immediate emergency medical care if you experience signs of: