Dabigatran
Dabigatran Etexilate · Capsule · Oral
Uses
Dabigatran etexilate capsules are a direct thrombin inhibitor indicated: To reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation ( 1.1 ) For the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in adult patients who have been treated with a parenteral anticoagulant for 5-10 days ( 1.2 ) To reduce the risk of recurrence of DVT and PE in adult patients who have been previously treated ( 1.3 ) For the prophylaxis of DVT and PE in adult patients who have undergone hip replacement surgery ( 1.4 ) 1.1 Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients Dabigatran etexilate capsules are indicated to reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation. 1.2 Treatment of Deep Venous Thrombosis and Pulmonary Embolism in Adult Patients Dabigatran etexilate capsules are indicated 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. 1.3 Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism in Adult Patients Dabigatran etexilate capsules are indicated to reduce the risk of recurrence of deep venous thrombosis and pulmonary embolism in adult patients who have been previously treated. 1.4 Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism in Adult Patients Following Hip Replacement Surgery Dabigatran etexilate capsules are indicated for the prophylaxis of deep vein thrombosis and pulmonary embolism, in adult patients who have undergone hip replacement surgery. Pediatric use information is approved for Boehringer Ingelheim Pharmaceuticals, Inc.’s Pradaxa (dabigatran etexilate) capsules. However, due to Boehringer Ingelheim Pharmaceuticals, Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.
Dosage and administration
• Non-valvular Atrial Fibrillation in Adult Patients : o For patients with CrCl >30 mL/min: 150 mg orally, twice daily ( 2.2 ) o For patients with CrCl 15 to 30 mL/min: 75 mg orally, twice daily ( 2.2 )
• Treatment of DVT and PE in Adult Patients : o For patients with CrCl > 30 mL/min: 150 mg orally, twice daily after 5-10 days of parenteral anticoagulation ( 2.2 )
• Reduction in the Risk of Recurrence of DVT and PE in Adult Patients: o For patients with CrCl > 30 mL/min: 150 mg orally, twice daily after previous treatment ( 2.2 )
• Prophylaxis of DVT and PE Following Hip Replacement Surgery in Adult Patients: o For patients with CrCl > 30 mL/min: 110 mg orally first day, then 220 mg once daily ( 2.2 )
• Dabigatran etexilate Capsules are NOT substitutable on a milligram-to-milligram basis with other dabigatran etexilate dosage forms
• Review recommendations for converting to or from other oral or parenteral anticoagulants ( 2.6 , 2.7 )
• Temporarily discontinue dabigatran etexilate capsules before invasive or surgical procedures when possible, then restart promptly ( 2.8 ) 2.1 Important Dosage Information Dabigatran etexilate is available in different dosage forms and not all dosage forms are approved for the same indications and age groups. In addition, there are differences between the dosage forms with respect to dosing due to differences in bioavailability. Do not substitute different dosage forms on a milligram-to-milligram basis and do not combine more than one dosage form to achieve the total dose [see Clinical Pharmacology (12.3) ]. 2.2 Recommended Dabigatran etexilate Capsules Dosage for Adults Indication Dosage Reduction in Risk of Stroke and Systemic Embolism in Non-valvular AF CrCl > 30 mL/min: 150 mg twice daily CrCl 15 to 30 mL/min: 75 mg twice daily CrCl < 15 mL/min or on dialysis: Dosing recommendations cannot be provided CrCl 30 to 50 mL/min with concomitant use of P-gp inhibitors: Reduce dosage to 75 mg twice daily if given with P-gp inhibitors dronedarone or systemic ketoconazole. CrCl < 30 mL/min with concomitant use of P-gp inhibitors: Avoid co-administration Treatment of DVT and PE Reduction in the Risk of Recurrence of DVT and PE CrCl > 30 mL/min: 150 mg twice daily CrCl ≤ 30 mL/min or on dialysis: Dosing recommendations cannot be provided CrCl < 50 mL/min with concomitant use of P-gp inhibitors: Avoid co-administration Prophylaxis of DVT and PE Following Hip Replacement Surgery CrCl > 30 mL/min: 110 mg for first day, then 220 mg once daily CrCl ≤ 30 mL/min or on dialysis: Dosing recommendations cannot be provided CrCl <50 mL/min with concomitant use of P-gp inhibitors: Avoid co-administration Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients For patients with creatinine clearance (CrCl) > 30 mL/min, the recommended dosage of dabigatran etexilate capsules are 150 mg taken orally, twice daily. For patients with severe renal impairment (CrCl 15 to 30 mL/min), the recommended dosage of dabigatran etexilate capsules are 75 mg twice daily [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )]. Dosing recommendations for patients with a CrCl < 15 mL/min or on dialysis cannot be provided. Treatment of Deep Venous Thrombosis and Pulmonary Embolism in Adult Patients For patients with CrCl > 30 mL/min, the recommended dosage of dabigatran etexilate capsules are 150 mg taken orally, twice daily, after 5-10 days of parenteral anticoagulation. Dosing recommendations for patients with a CrCl ≤ 30 mL/min or on dialysis cannot be provided [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )]. Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism in Adult Patients For patients with CrCl >30 mL/min, the recommended dose of dabigatran etexilate capsules are 150 mg taken orally, twice daily after previous treatment. Dosing recommendations for patients with a CrCl ≤30 mL/min or on dialysis cannot be provided [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )]. Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism in Adult Patients Following Hip Replacement Surgery For patients with CrCl > 30 mL/min, the recommended dosage of dabigatran etexilate capsules are 110 mg taken orally 1-4 hours after surgery and after hemostasis has been achieved, then 220 mg taken once daily for 28-35 days. If dabigatran etexilate capsule is not started on the day of surgery, after hemostasis has been achieved initiate treatment with 220 mg once daily. Dosing recommendations for patients with a CrCl ≤ 30 mL/min or on dialysis cannot be provided [see Dosage and Administration ( 2.4 ), Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.2 , 12.3 )]. Pediatric use information is approved for Boehringer Ingelheim Pharmaceuticals, Inc.’s Pradaxa (dabigatran etexilate) capsules. However, due to Boehringer Ingelheim Pharmaceuticals, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. 2.4 Dosage Adjustments Adult patients with renal impairment Assess renal function prior to initiation of treatment with dabigatran etexilate capsules. Periodically assess renal function as clinically indicated (i.e., more frequently in clinical situations that may be associated with a decline in renal function) and adjust therapy accordingly. Discontinue dabigatran etexilate capsules in patients who develop acute renal failure while on dabigatran etexilate capsules and consider alternative anticoagulant therapy. Generally, in adult patients the extent of anticoagulation does not need to be assessed. When necessary, use aPTT or ECT, and not INR, to assess for anticoagulant activity in adult patients on dabigatran etexilate capsules [see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.2 )].
Dosage forms and strengths
150 mg capsules with a white to light yellow colored blend compressing granular powder, pellets in size “0” capsule having white opaque cap imprinted “MD” and white opaque body imprinted with “150” with black ink. 110 mg capsules with a white to light yellow colored blend compressing granular powder, pellets in size “1” capsule having white opaque cap imprinted “MD” and white opaque body imprinted with “110” with black ink. 75 mg capsules with a white to light yellow colored blend compressing granular powder, pellets in size “2” capsule having white opaque cap imprinted “MD” and white opaque body imprinted with “75” with black ink. Capsules: 75 mg, 110 mg and 150 mg ( 3 )
Contraindications
Dabigatran is contraindicated in patients with:
• Active pathological bleeding [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.1 )]
• 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) [see Adverse Reactions ( 6.1 )]
• Mechanical prosthetic heart valve [see Warnings and Precautions ( 5.4 )]
• Active pathological bleeding ( 4 )
• History of serious hypersensitivity reaction to dabigatran ( 4 )
• Mechanical prosthetic heart valve ( 4 )
Warnings and precautions
• Bleeding: Dabigatran can cause serious and fatal bleeding ( 5.2 )
• Bioprosthetic heart valves: Dabigatran use not recommended ( 5.4 )
• Increased Risk of Thrombosis in Patients with Triple-Positive Antiphospholipid Syndrome: Dabigatran use not recommended ( 5.6 ) 5.1 Increased Risk of Thrombotic Events after Premature Discontinuation Premature discontinuation of any oral anticoagulant, including dabigatran, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. If dabigatran etexilate capsules is 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 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 )]. Risk factors for bleeding include the concomitant use of other drugs that increase the risk of bleeding (e.g., anti-platelet agents, heparin, fibrinolytic therapy, and chronic use of NSAIDs). Dabigatran's anticoagulant activity and half-life are increased in patients with renal impairment [see Clinical Pharmacology ( 12.2 )]. Reversal of Anticoagulant Effect: In adults, 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 In pediatric patients, the efficacy and safety of idarucizumab have not been established. Hemodialysis can remove dabigatran; however the clinical experience supporting the use of hemodialysis as a treatment for bleeding is limited [see Overdosage ( 10 )]. Prothrombin complex concentrates, or recombinant Factor VIIa may be considered but their use has not been evaluated in clinical trials. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of dabigatran. Consider administration of platelet concentrates in cases where thrombocytopenia is present or long-acting antiplatelet drugs have been used. 5.3 Spinal/Epidural Anesthesia or Puncture When neuraxial anesthesia (spinal/epidural anesthesia) or spinal puncture is employed, patients treated with anticoagulant agents are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis [see Boxed Warning ]. To reduce the potential risk of bleeding associated with the concurrent use of dabigatran and epidural or spinal anesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of dabigatran [see Clinical Pharmacology ( 12.3 )] . Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of dabigatran is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known. Should the physician decide to administer anticoagulation in the context of epidural or spinal anesthesia/analgesia or lumbar puncture, monitor frequently to detect any signs or symptoms of neurological impairment, such as midline back pain, sensory and motor deficits (numbness, tingling, or weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to immediately report if they experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae. 5.4 Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves The safety and efficacy of dabigatran etexilate capsules in adult patients with bileaflet mechanical prosthetic heart valves was evaluated in the RE-ALIGN trial, in which patients with bileaflet mechanical prosthetic heart valves (recently implanted or implanted more than three months prior to enrollment) were randomized to dose-adjusted warfarin or 150 mg, 220 mg, or 300 mg of dabigatran etexilate capsules twice a day. RE-ALIGN was terminated early due to the occurrence of significantly more thromboembolic events (valve thrombosis, stroke, transient ischemic attack, and myocardial infarction) and an excess of major bleeding (predominantly post-operative pericardial effusions requiring intervention for hemodynamic compromise) in the dabigatran etexilate capsules treatment arm as compared to the warfarin treatment arm. These bleeding and thromboembolic events were seen both in patients who were initiated on dabigatran etexilate capsules postoperatively within three days of mechanical bileaflet valve implantation, as well as in patients whose valves had been implanted more than three months prior to enrollment. Therefore, the use of dabigatran is contraindicated in all patients with mechanical prosthetic valves [see Contraindications ( 4 )]. The use of dabigatran for the prophylaxis of thromboembolic events in patients with atrial fibrillation in the setting of other forms of valvular heart disease, including the presence of a bioprosthetic heart valve, has not been studied and is not recommended. 5.5 Effect of P-gp Inducers and Inhibitors on Dabigatran Exposure The concomitant use of dabigatran with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided [see Clinical Pharmacology ( 12.3 )]. P-gp inhibition and impaired renal function are the major independent factors that result in increased exposure to dabigatran [see Clinical Pharmacology ( 12.3 )].
Side effects
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 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 Novadoz Pharmaceuticals LLC at 1-855-668-2369 or 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 2. 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. Intracranial hemorrhage included intracerebral (hemorrhagic stroke), subarachnoid, and subdural bleeds. Table 3 Adjudicated Major Bleeding Events in Treated Patientsa Event Dabigatran etexilate capsules 150 mg N = 6,059 n (%/yearb) Warfarin N = 5,998 n (%/yearb) Dabigatran etexilate capsules 150 mg vs Warfarin HR (95% CI) Major Bleedingc 350 (3.47) 374 (3.58) 0.97 (0.84, 1.12) Intracranial Hemorrhage (ICH)d 23 (0.22) 82 (0.77) 0.29 (0.18, 0.46) Hemorrhagic Strokee 6 (0.06) 40 (0.37) 0.16 (0.07, 0.37) Other ICH 17 (0.17) 46 (0.43) 0.38 (0.22, 0.67) Gastrointestinal 162 (1.59) 111 (1.05) 1.51 (1.19, 1.92) Fatal Bleedingf 7 (0.07) 16 (0.15) 0.45 (0.19, 1.10) ICH 3 (0.03) 9 (0.08) 0.35 (0.09, 1.28) Non-intracranialg 4 (0.04) 7 (0.07) 0.59 (0.17, 2.02) a Patients during treatment or within 2 days of stopping study treatment. Major bleeding events within each subcategory were counted once per patient, but patients may have contributed events to multiple subcategories. b Annual event rate per 100 pt-years = 100 * number of subjects with event/subject-years. Subject-years is defined as cumulative number of days from first drug intake to event date, date of last drug intake + 2, death date (whatever occurred first) across all treated subjects divided by 365.25. In case of recurrent events of the same category, the first event was considered. c Defined as bleeding accompanied by one or more of the following: a decrease in hemoglobin of ≥ 2 g/dL, a transfusion of 2 or more units of packed red blood cells, bleeding at a critical site or with fatal outcome. d Intracranial bleed included intracerebral (hemorrhagic stroke), subarachnoid, and subdural bleeds. e On-treatment analysis based on the safety population, compared to ITT analysis presented in Section 14 Clinical Studies. f Fatal bleed: Adjudicated major bleed as defined above with investigator reported fatal outcome and adjudicated death with primary cause from bleeding. g Non-intracranial fatal bleed: Adjudicated major bleed as defined above and adjudicated death with primary cause from bleeding but without symptomatic intracranial bleed based on investigator’s clinical assessment. There was a higher rate of any gastrointestinal bleeds in patients receiving dabigatran etexilate capsules 150 mg than in patients receiving warfarin (6.6% vs 4.2%, respectively). The risk of major bleeds was similar with dabigatran etexilate capsules 150 mg and warfarin across major subgroups defined by baseline characteristics (see Figure 1), with the exception of age, where there was a trend toward a higher incidence of major bleeding on dabigatran etexilate capsules (hazard ratio 1.2, 95% CI: 1.0 to 1.5) for patients ≥75 years of age. Figure 1 Adjudicated Major Bleeding by Baseline Characteristics Including Hemorrhagic Stroke Treated Patients Note: The figure above presents effects in various subgroups all of which are baseline characteristics and all of which were pre-specified.
Drug interactions
• P-gp inducers: Avoid coadministration with dabigatran ( 5.5 )
• P-gp inhibitors in adult patients with CrCl 30 to 50 mL/min: Reduce dose or avoid ( 7 )
• P-gp inhibitors in adult patients with CrCl <30 mL/min: Not recommended ( 7 ) 7.1 Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients The concomitant use of dabigatran with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided [see Clinical Pharmacology ( 12.3 )]. P-gp inhibition and impaired renal function are the major independent factors that result in increased exposure to dabigatran [see Clinical Pharmacology ( 12.3 )]. Concomitant use of P-gp inhibitors in patients with renal impairment is expected to produce increased exposure of dabigatran compared to that seen with either factor alone. In patients with moderate renal impairment (CrCl 30 to 50 mL/min), reduce the dosage of dabigatran to 75 mg twice daily when administered concomitantly with the P-gp inhibitors dronedarone or systemic ketoconazole. The use of the P-gp inhibitors verapamil, amiodarone, quinidine, clarithromycin, and ticagrelor does not require a dosage adjustment of dabigatran. These results should not be extrapolated to other P-gp inhibitors [see Warnings and Precautions ( 5.5 ), Use in Specific Populations ( 8.6 ), and Clinical Pharmacology ( 12.3 )]. The concomitant use of dabigatran and P-gp inhibitors in patients with severe renal impairment (CrCl 15 to 30 mL/min) should be avoided [see Warnings and Precautions ( 5.5 ), Use in Specific Populations ( 8.6 ), and Clinical Pharmacology ( 12.3 )]. 7.2 Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism in Adult Patients Avoid use of dabigatran and P-gp inhibitors in patients with CrCl < 50 mL/min [see Warnings and Precautions (5.5), Use in Specific Populations ( 8.6 ), and Clinical Pharmacology ( 12.3 )]. 7.3 Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism in Adult Patients Following Hip Replacement Surgery In patients with CrCl ≥ 50 mL/min who have concomitant administration of P-gp inhibitors such as dronedarone or systemic ketoconazole, it may be helpful to separate the timing of administration of dabigatran and the P-gp inhibitor by several hours. The concomitant use of dabigatran and P-gp inhibitors in patients with CrCl <50 mL/min should be avoided [see Warnings and Precautions ( 5.5 ), Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.2 , 12.3 )]. Pediatric use information is approved for Boehringer Ingelheim Pharmaceuticals, Inc.’s Pradaxa (dabigatran etexilate) capsules. However, due to Boehringer Ingelheim Pharmaceuticals, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
Use in specific populations
Lactation: Breastfeeding not recommended ( 8.2 ) Geriatric Use: Risk of bleeding increases with age ( 8.5 ) Pediatric use information is approved for Boehringer Ingelheim Pharmaceuticals, Inc.'s Pradaxa (dabigatran etexilate) capsules. However, due to Boehringer Ingelheim Pharmaceuticals, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. 8.1 Pregnancy Risk Summary The limited available data on dabigatran use in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes. There are risks to the mother associated with untreated venous thromboembolism in pregnancy and a risk of hemorrhage in the mother and fetus associated with the use of anticoagulants (see Clinical Considerations ) . In pregnant rats treated from implantation until weaning, dabigatran increased the number of dead offspring and caused excess vaginal/uterine bleeding close to parturition at an exposure 2.6 times the human exposure. At a similar exposure, dabigatran decreased the number of implantations when rats were treated prior to mating and up to implantation (gestation Day 6). Dabigatran administered to pregnant rats and rabbits during organogenesis up to exposures 8 and 13 times the human exposure, respectively, did not induce major malformations. However, the incidence of delayed or irregular ossification of fetal skull bones and vertebrae was increased in the rat (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions. Published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy. Fetal/Neonatal adverse reaction Use of anticoagulants, including dabigatran, may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding [see Warnings and Precautions ( 5.2 )]. Labor or delivery All patients receiving anticoagulants, including pregnant women, are at risk for bleeding. Dabigatran use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas. Consider discontinuation or use of shorter acting anticoagulant as delivery approaches [see Warnings and Precautions ( 5.2 , 5.3 )]. Data Animal Data Dabigatran has been shown to decrease the number of implantations when male and female rats were treated at a dosage of 70 mg/kg (about 2.6 to 3.0 times the human exposure at MRHD of 300 mg/day based on area under the curve [AUC] comparisons) prior to mating and up to implantation (gestation Day 6). Treatment of pregnant rats after implantation with dabigatran at the same dose increased the number of dead offspring and caused excess vaginal/uterine bleeding close to parturition. Dabigatran administered to pregnant rats and rabbits during organogenesis up to maternally toxic doses of 200 mg/kg (8 and 13 times the human exposure, respectively, at a MRHD of 300 mg/day based on AUC comparisons) did not induce major malformations, but increased the incidence of delayed or irregular ossification of fetal skull bones and vertebrae in the rat. Death of offspring and mother rats during labor in association with uterine bleeding occurred during treatment of pregnant rats from implantation (gestation Day 7) to weaning (lactation Day 21) with dabigatran at a dose of 70 mg/kg (about 2.6 times the human exposure at MRHD of 300 mg/day based on AUC comparisons). 8.2 Lactation Risk Summary There are no data on the presence of dabigatran in human milk, the effects on the breastfed child, or on milk production. Dabigatran and/or its metabolites were present in rat milk. Breastfeeding is not recommended during treatment with dabigatran. 8.3 Females and Males of Reproductive Potential Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including dabigatran should be assessed in females of reproductive potential and those with abnormal uterine bleeding. 8.4 Pediatric Use Safety and effectiveness of dabigatran etexilate capsules have not been established in pediatric patients with non-valvular atrial fibrillation or those who have undergone hip replacement surgery. Pediatric use information is approved for Boehringer Ingelheim Pharmaceuticals, Inc.’s Pradaxa (dabigatran etexilate) capsules. However, due to Boehringer Ingelheim Pharmaceuticals, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. 8.5 Geriatric Use Of the total number of patients in the RE-LY study, 82% were 65 and over, while 40% were 75 and over. The risk of stroke and bleeding increases with age, but the risk-benefit profile is favorable in all age groups [see Warnings and Precautions ( 5 ), Adverse Reactions ( 6.1 ), and Clinical Studies ( 14.1 )]. 8.6 Renal Impairment Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients No dose adjustment of dabigatran is recommended in patients with mild or moderate renal impairment [see Clinical Pharmacology ( 12.3 )]. Reduce the dose of dabigatran in patients with severe renal impairment (CrCl 15 to 30 mL/min) [see Dosage and Administration ( 2.2 , 2.4 ) and Clinical Pharmacology ( 12.3 )].
Pregnancy
8.1 Pregnancy Risk Summary The limited available data on dabigatran use in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes. There are risks to the mother associated with untreated venous thromboembolism in pregnancy and a risk of hemorrhage in the mother and fetus associated with the use of anticoagulants (see Clinical Considerations ) . In pregnant rats treated from implantation until weaning, dabigatran increased the number of dead offspring and caused excess vaginal/uterine bleeding close to parturition at an exposure 2.6 times the human exposure. At a similar exposure, dabigatran decreased the number of implantations when rats were treated prior to mating and up to implantation (gestation Day 6). Dabigatran administered to pregnant rats and rabbits during organogenesis up to exposures 8 and 13 times the human exposure, respectively, did not induce major malformations. However, the incidence of delayed or irregular ossification of fetal skull bones and vertebrae was increased in the rat (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions. Published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy. Fetal/Neonatal adverse reaction Use of anticoagulants, including dabigatran, may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding [see Warnings and Precautions ( 5.2 )]. Labor or delivery All patients receiving anticoagulants, including pregnant women, are at risk for bleeding. Dabigatran use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas. Consider discontinuation or use of shorter acting anticoagulant as delivery approaches [see Warnings and Precautions ( 5.2 , 5.3 )]. Data Animal Data Dabigatran has been shown to decrease the number of implantations when male and female rats were treated at a dosage of 70 mg/kg (about 2.6 to 3.0 times the human exposure at MRHD of 300 mg/day based on area under the curve [AUC] comparisons) prior to mating and up to implantation (gestation Day 6). Treatment of pregnant rats after implantation with dabigatran at the same dose increased the number of dead offspring and caused excess vaginal/uterine bleeding close to parturition. Dabigatran administered to pregnant rats and rabbits during organogenesis up to maternally toxic doses of 200 mg/kg (8 and 13 times the human exposure, respectively, at a MRHD of 300 mg/day based on AUC comparisons) did not induce major malformations, but increased the incidence of delayed or irregular ossification of fetal skull bones and vertebrae in the rat. Death of offspring and mother rats during labor in association with uterine bleeding occurred during treatment of pregnant rats from implantation (gestation Day 7) to weaning (lactation Day 21) with dabigatran at a dose of 70 mg/kg (about 2.6 times the human exposure at MRHD of 300 mg/day based on AUC comparisons).
Pediatric use
8.5 Geriatric Use Of the total number of patients in the RE-LY study, 82% were 65 and over, while 40% were 75 and over. The risk of stroke and bleeding increases with age, but the risk-benefit profile is favorable in all age groups [see Warnings and Precautions ( 5 ), Adverse Reactions ( 6.1 ), and Clinical Studies ( 14.1 )].
Geriatric use
8.6 Renal Impairment Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients No dose adjustment of dabigatran is recommended in patients with mild or moderate renal impairment [see Clinical Pharmacology ( 12.3 )]. Reduce the dose of dabigatran in patients with severe renal impairment (CrCl 15 to 30 mL/min) [see Dosage and Administration ( 2.2 , 2.4 ) and Clinical Pharmacology ( 12.3 )]. Dosing recommendations for patients with CrCl < 15 mL/min or on dialysis cannot be provided. Adjust dose appropriately in patients with renal impairment receiving concomitant P-gp inhibitors [see Warnings and Precautions ( 5.5 ), Drug Interactions ( 7.1 ), and Clinical Pharmacology ( 12.3 )]. Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism in Adult Patients Patients with severe renal impairment (CrCl ≤ 30 mL/min) were excluded from RE-COVER. Dosing recommendations for patients with CrCl ≤ 30 mL/min or on dialysis cannot be provided. Avoid use of dabigatran with concomitant P-gp inhibitors in patients with CrCl < 50 mL/min [see Warnings and Precautions ( 5.5 ), Drug Interactions ( 7.2 ), and Clinical Pharmacology ( 12.3 )]. Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism in Adult Patients Following Hip Replacement Surgery Patients with severe renal impairment (CrCl < 30 mL/min) were excluded from RE-NOVATE and RE-NOVATE II. Dosing recommendations for patients with CrCl < 30 mL/min or on dialysis cannot be provided. Avoid use of dabigatran with concomitant P-gp inhibitors in patients with CrCl < 50 mL/min [see Warnings and Precautions ( 5.5 ), Drug Interactions ( 7.3 ) and Clinical Pharmacology ( 12.2 , 12.3 )]. Pediatric use information is approved for Boehringer Ingelheim Pharmaceuticals, Inc.’s Pradaxa (dabigatran etexilate) capsules. However, due to Boehringer Ingelheim Pharmaceuticals, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
Overdosage
Accidental overdose may lead to hemorrhagic complications. In the event of hemorrhagic complications, initiate appropriate clinical support, discontinue treatment with dabigatran, and investigate the source of bleeding. A specific reversal agent (idarucizumab) is available for adult patients. Dabigatran is primarily eliminated by the kidneys with a low plasma protein binding of approximately 35%. Hemodialysis can remove dabigatran; however, data supporting this approach are limited. Using a high-flux dialyzer, blood flow rate of 200 mL/min, and dialysate flow rate of 700 mL/min, approximately 49% of total dabigatran can be cleared from plasma over 4 hours. At the same dialysate flow rate, approximately 57% can be cleared using a dialyzer blood flow rate of 300 mL/min, with no appreciable increase in clearance observed at higher blood flow rates. Upon cessation of hemodialysis, a redistribution effect of approximately 7% to 15% is seen. The effect of dialysis on dabigatran’s plasma concentration would be expected to vary based on patient specific characteristics. Measurement of aPTT or ECT may help guide therapy [see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.2 )].
Description
The chemical name for dabigatran etexilate mesylate, a direct thrombin inhibitor, is β-Alanine,N-[[2-[[[4-[[[(hexyloxy)carbonyl]amino]iminomethyl]phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl-,ethyl ester, methanesulfonate. The molecular formula is C 35 H 45 N 7 O 8 S and the molecular weight is 723.86 (mesylate salt), 627.75 (free base). The structural formula is: Dabigatran etexilate mesylate is a yellow-white to yellow powder. It is freely soluble in methanol, soluble in ethanol, and practically insoluble in ethyl acetate. Dabigatran etexilate capsules are supplied in 75 mg, 110 mg and 150 mg strengths for oral administration. Each capsule contains dabigatran etexilate mesylate as the active ingredient: 150 mg dabigatran etexilate (equivalent to 172.95 mg dabigatran etexilate mesylate), 110 mg dabigatran etexilate (equivalent to 126.83 mg dabigatran etexilate mesylate), or 75 mg dabigatran etexilate (equivalent to 86.48 mg dabigatran etexilate mesylate) along with the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, magnesium stearate, talc, tartaric acid pellets. The capsule shell is composed of hypromellose, titanium dioxide. The imprinting ink contains black iron oxide, propylene glycol, potassium hydroxide and shellac. dabigatran-etexilate-structure
Mechanism of action
12.1 Mechanism of Action Dabigatran and its acyl glucuronides are competitive, direct thrombin inhibitors. Because thrombin (serine protease) enables the conversion of fibrinogen into fibrin during the coagulation cascade, its inhibition prevents the development of a thrombus. Both free and clot-bound thrombin, and thrombin-induced platelet aggregation are inhibited by the active moieties.
How supplied
Dabigatran etexilate capsules 75 mg capsules have a white to light yellow colored blend compressing granular powder, pellets in size “2” capsule having white opaque cap imprinted “MD” and white opaque body imprinted with “75” with black ink. The capsules are supplied in the packages listed:
• NDC 72205-202-60 Unit of use bottle of 60 capsules
• NDC 72205-202-34 Blister package containing 60 capsules (6 x 10 capsule blister cards) Dabigatran etexilate capsules 110 mg capsules have a white to light yellow colored blend compressing granular powder, pellets in size “1” capsule having white opaque cap imprinted “MD” and white opaque body imprinted with “110” with black ink. The capsules are supplied in the packages listed:
• NDC 72205-203-60 Unit of use bottle of 60 capsules
• NDC 72205-203-34 Blister package containing 60 capsules (6 x 10 capsule blister cards) Dabigatran etexilate capsules 150 mg capsules have a white to light yellow colored blend compressing granular powder, pellets in size “0” capsule having white opaque cap imprinted “MD” and white opaque body imprinted with “150” with black ink. The capsules are supplied in the packages listed:
• NDC 72205-204-60 Unit of use bottle of 60 capsules
• NDC 72205-204-34 Blister package containing 60 capsules (6 x 10 capsule blister cards) Bottles Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Once opened, the product must be used within 4 months. Keep the bottle tightly closed. Store in the original package to protect from moisture. Blisters Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Store in the original package to protect from moisture. Keep out of the reach of children.
Patient information
Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide). Instructions for Patients Tell patients to take dabigatran etexilate capsules exactly as prescribed. Remind patients not to discontinue dabigatran etexilate capsules without talking to the healthcare provider who prescribed it. Keep dabigatran etexilate capsules in the original bottle to protect from moisture. Do not put dabigatran etexilate capsules in pill boxes or pill organizers. When more than one bottle is dispensed to the patient, instruct them to open only one bottle at a time. Instruct patient to remove only one capsule from the opened bottle at the time of use. The bottle should be immediately and tightly closed. Advise patients not to chew or break the capsules before swallowing them and not to open the capsules and take the pellets alone. Advise patients that the capsule should be taken with a full glass of water. [ see Boxed Warning, Dosage and Administration (2.5 )] Bleeding Inform patients that they may bleed more easily, may bleed longer, and should call their healthcare provider for any signs or symptoms of bleeding [ see Warnings and Precautions (5.2)]. Instruct patients to seek emergency care right away if they have any of the following, which may be a sign or symptom of serious bleeding:
• Unusual bruising (bruises that appear without known cause or that get bigger)
• Pink or brown urine
• Red or black, tarry stools
• Coughing up blood
• Vomiting blood, or vomit that looks like coffee grounds Instruct patients to call their healthcare provider or to get prompt medical attention if they experience any signs or symptoms of bleeding:
• Pain, swelling or discomfort in a joint
• Headaches, dizziness, or weakness
• Reoccurring nose bleeds
• Unusual bleeding from gums
• Bleeding from a cut that takes a long time to stop
• Menstrual bleeding or vaginal bleeding that is heavier than normal If patients have had neuraxial anesthesia or spinal puncture, and particularly, if they are taking concomitant NSAIDs or platelet inhibitors, advise patients to watch for signs and symptoms of spinal or epidural hematoma, such as back pain, tingling, numbness (especially in the lower limbs), muscle weakness, and stool or urine incontinence. If any of these symptoms occur, advise the patient to contact his or her physician immediately [see Boxed Warning ]. Gastrointestinal Adverse Reactions Instruct patients to call their healthcare provider if they experience any signs or symptoms of dyspepsia or gastritis: Dyspepsia (upset stomach), burning, or nausea Abdominal pain or discomfort Epigastric discomfort, GERD (gastric indigestion) [ see Adverse Reactions (6.1)] Invasive or Surgical Procedures Instruct patients to inform their healthcare provider that they are taking dabigatran before any invasive procedure (including dental procedures) is scheduled [see Dosage and Administration (2.8) ]. Concomitant Medications Ask patients to list all prescription medications, over-the-counter medications, or dietary supplements they are taking or plan to take so their healthcare provider knows about other treatments that may affect bleeding risk (e.g., aspirin or NSAIDs) or dabigatran exposure (e.g., dronedarone or systemic ketoconazole) [ see Warnings and Precautions (5.2, 5.5)]. Prosthetic Heart Valves Instruct patients to inform their healthcare provider if they will have or have had surgery to place a prosthetic heart valve [ see Warnings and Precautions ( 5.4)]. Allergic Reactions Advise adult patients and caregivers that some adults taking dabigatran have developed symptoms of an allergic reaction. Advise adult patients or caregivers to inform their healthcare provider if they develop symptoms of an allergic reaction, such as hives, rash, or itching. Advise adult patients or caregivers to seek emergency medical attention if they develop chest pain or tightness, swelling of the face or tongue, trouble breathing or wheezing, or feeling dizzy or faint. Pregnancy Advise patients to inform their healthcare provider immediately if they become pregnant or intend to become pregnant during treatment with dabigatran [ see Use in Specific Populations (8.1)]. Lactation Advise patients not to breastfeed if they are taking dabigatran etexilate capsules [ see Use in Specific Populations (8.2)]. Pediatric use information is approved for Boehringer Ingelheim Pharmaceuticals, Inc.’s Pradaxa (dabigatran etexilate) capsules. However, due to Boehringer Ingelheim Pharmaceuticals, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. Dispense with Medication Guide available at: www.NovadozPharma.com/Products Manufactured by: MSN Laboratories Private Limited Telangana – 509 228, INDIA Distributed by: Novadoz Pharmaceuticals LLC Piscataway, NJ 08854 -3714 Issued on: October 2024
Label text from the FDA structured product label by Novadoz Pharmaceuticals LLC (revised Feb 6, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Dabigatran Etexilate Mesylate in 10 products
Dabigatran NDC products (10)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-7530 | Dabigatran Etexilate Mesylate 150 mg/1 Capsule | A-S Medication Solutions | ANDA |
| 50090-7531 | Dabigatran Etexilate Mesylate 75 mg/1 Capsule | A-S Medication Solutions | ANDA |
| 60687-963 | Dabigatran Etexilate Mesylate 75 mg/1 Capsule | American Health Packaging | ANDA |
| 60687-974 | Dabigatran Etexilate Mesylate 150 mg/1 Capsule | American Health Packaging | ANDA |
| 42291-033 | Dabigatran Etexilate Mesylate 75 mg/1 Capsule | AvKARE | ANDA |
| 42291-034 | Dabigatran Etexilate Mesylate 150 mg/1 Capsule | AvKARE | ANDA |
| 50268-200 | Dabigatran Etexilate Mesylate 150 mg/1 Capsule | AvPAK | ANDA |
| 72205-202 | Dabigatran Etexilate Mesylate 75 mg/1 Capsule | Novadoz Pharmaceuticals LLC | ANDA |
| 72205-203 | Dabigatran Etexilate Mesylate 110 mg/1 Capsule | Novadoz Pharmaceuticals LLC | ANDA |
| 72205-204 | Dabigatran Etexilate Mesylate 150 mg/1 Capsule | Novadoz Pharmaceuticals LLC | ANDA |
Frequently asked questions
What is Dabigatran used for?
Dabigatran etexilate capsules are a direct thrombin inhibitor indicated: To reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation ( 1.1 ) For the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in adult patients who have been treated with a parenteral anticoagulant for 5-10 days ( 1.2 ) To reduce the risk of recurrence of DVT…
What are the side effects of Dabigatran?
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… See the full label for the complete list.
Who makes Dabigatran?
Dabigatran is listed by 5 labelers in the FDA NDC directory, including A-S Medication Solutions, American Health Packaging, AvKARE, AvPAK.