Dabigatran

471.521

471.51

I0VM4M70GC

DTXSID50175419

White crystals

150

0.79

Tan solid

1.4±0.1 g/cm3

276-277 °C

797.1±70.0 °C at 760 mmHg

435.9±35.7 °C

1.694

Refrigerator, Under Inert Atmosphere

9.4X10-19 mm Hg at 25 deg C (est)

pKa1 = 1.82 (pyridine); pKa2 = 3.18 (imidazole); pKa3 = 4.28 (carboxylic acid); pKa4 = 11.52 (amine) (est)

Yellow-white to yellow powder. A saturated solution in pure water has a solubilty of 1.8 mg/L. It is freely soluble in methanol, slightly soluble in ethanol, and sparingly soluble in isopropanol. /Dabigatran etexilate mesylate/|Colorless crystals, mp 128-129 °C. Log P (n-octanol/buffer, pH 7.4) 2.6 /Dabigatran etexilate/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including dabigatran etexilate mesylate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Dabigatran extexilate mesylate/

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Dipyridamole has been associated with a low rate of serum enzyme elevations during therapy, but in large clinical trials the frequency of liver enzyme abnormalities was similar with dipyridamole therapy as with placebo. Cases of clinically apparent acute liver injury from dipyridamole have not been published although hepatitis is listed as a potential side effect in the product label. The clinical features of the liver injury linked to dipyridamole have not been described.|Chronic therapy with dabigatran is associated with moderate ALT elevations (greater than 3 times the upper limit of normal) in 1.5% to 3% of patients, an overall rate which is slightly lower than with low molecular weight heparin and similar to the rates with warfarin. While case reports of clinically apparent liver injury due to dabigatran have not been published, several instances of ALT elevations with jaundice occurred during the large, prelicensure clinical trials of dabigatran. These cases were mild and self-limited, resolving completely once therapy was stopped. However, other causes of liver injury could not always be identified and the relationship of the injury to dabigatran therapy remains unclear. The clinical features of these cases were not described. In one large clinical trial, these unexplained cases of liver injury with bilirubin elevations occurred in approximately 1 in 2000 patients treated. In a subsequent case report, liver injury with jaundice and a mixed pattern of serum enzyme elevations arose within 4 weeks of starting dabigatran and resolved rapidly with its discontinuation. Immunoallergic and autoimmune features were not present. There have been multiple spontaneous reports of liver injury, some of which were fatal, made to WHO and FDA surveillance databases, but the relatedness of the episodes has not been clearly defined. Thus, clinically apparent liver injury with jaundice due to dabigatran occurs but is rare and typically mild and self-limited.

The concomitant use of a CYP3A4 isoenzyme substrate (atorvastatin) and dabigatran did not have clinically relevant effects on the pharmacokinetics of either drug. Also, the concomitant use of a CYP2C9 substrate (diclofenac) and dabigatran did not have clinically relevant effects on the pharmacokinetics of either drug.|Administration of rifampin for 7 days followed by a single dose of dabigatran resulted in decreases of 66 and 67% in dabigatran area under the plasma concentration-time curve (AUC) and peak plasma concentration, respectively. Within 7 days of rifampin discontinuance, dabigatran exposure approached levels expected without concurrent use of rifampin. Concomitant use should be avoided.|Concomitant use of dabigatran with P-glycoprotein inhibitors may increase systemic exposure to dabigatran. While clinical data and pharmacokinetic studies indicate that concomitant use of dabigatran with certain P-glycoprotein inhibitors (i.e., amiodarone, clarithromycin, ketoconazole, quinidine, verapamil) does not necessitate dosage adjustments, the manufacturer states that these results should not be extrapolated to all P-glycoprotein inhibitors.|Concomitant use of P-glycoprotein transport inhibitors and dabigatran in patients with renal impairment is expected to increase systemic exposure to dabigatran compared with that resulting from either factor alone. Reduction of dabigatran dosage should be considered in patients with moderate renal impairment (creatinine clearance of 30-50 mL/minute) who are receiving concomitant dronedarone or systemic ketoconazole. Concomitant use of dabigatran and P-glycoprotein transport inhibitors in patients with severe renal impairment (creatinine clearance of 15-30 mL/minute) should be avoided.|For more Interactions (Complete) data for Dabigatran (20 total), please visit the HSDB record page.

Dabigatran is contraindicated in patients with: active pathological bleeding; history of a serious hypersensitivity reaction to dabigatran (e.g., anaphylactic reaction or anaphylactic shock).

Dabigatran's production and use as an antithrombotic(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), estimated Koc values of 3600 and 30(SRC), determined respectively from a structure estimation method(2) and using an estimated log Kow of 1.95(2) and a regression-derived equation(2), indicates that dabigatran is expected to have slight to high mobility in soil(SRC). The contradiction may be explained by dabigatran's ability to protonate at environmental pHs(SRC). The estimated pKa values of 1.82, 3.18, 4.28 and 11.52(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because anions do not volatilize. Dabigatran is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.4X10-19 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Biodegradation data in soil were not available(SRC, 2012).|AQUATIC FATE: Based on a classification scheme(1), estimated Koc values of 3600 and 30(SRC), determined respectively from a structure estimation method(2) and using an estimated log Kow of 1.95(2) and a regression-derived equation(2), indicates that dabigatran may have strong to slight adsorption to suspended solids and sediment(SRC). The contradiction may be explained by dabigatran's ability to protonate at environmental pHs(SRC). The pKa values of 1.82, 3.18, 4.28 and 11.52(3) indicate dabigatran will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from the estimated log Kow(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2012).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dabigatran, which has an estimated vapor pressure of 9.4X10-19 mm Hg at 25 °C(SRC), determined from a fragment constant method(2) is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase dabigatran may be removed from the air by wet or dry deposition(SRC). Dabigatran contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Dabigatran is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Dabigatran contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for dabigatran(SRC), using an estimated log Kow of 1.95(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of dabigatran is estimated as 30(SRC), using an estimated log Kow of 1.95(1) and a regression-derived equation(1). Using a structure estimation method based on molecular connectivity indices(1), the Koc can be estimated to be 3600(SRC). According to a classification scheme(2), this estimated Koc value suggests that dabigatran is expected to have high to slight mobility in soil. The contradiction may be explained by dabigatran's ability to protonate at environmental pHs(SRC). Estimated pKa values of 1.82, 3.18, 4.28 and 11.52(3) indicate dabigatran will exist almost entirely in the anion form in the environment indicate dabigatran will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

Estimated pKa values of 1.82, 3.18, 4.28 and 11.52(1) indicate dabigatran will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. Dabigatran is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.4X10-19 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to dabigatran were not located(SRC, 2012), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Occupational exposure to dabigatran may occur through inhalation and dermal contact with this compound at workplaces where dabigatran is produced or used. Exposure to dabigatran among the general population may be limited to those administered the drug Pradaxa, a cardiac medication. (SRC)

To investigate the pharmacokinetic and pharmacodynamic profile of dabigatran in healthy elderly subjects; to assess the intra- and interindividual variability of dabigatran pharmacokinetics in order to assess possible gender differences ... 36 healthy elderly subjects (aged > or =65 years) with a body mass index of 18.5-29.9 kg/sq m. Subjects were randomized to receive dabigatran etexilate ... Dabigatran etexilate was administered as capsules at 150 mg twice daily over 6 days and once on the morning of day 7. ...The mean (SD) peak plasma concentrations on day 4 of treatment in male and female elderly subjects were 256 ng/mL (21.8) and 255 ng/mL (84.0), respectively.

Dipyridamole is a vasodilator and inhibitor of platelet aggregation that is used to decrease the risk of thromboembolic complications and recurrence of stroke in patients known to have atherosclerotic cerebrovascular disease. Dipyridamole is associated with a low rate of serum enzyme elevations during treatment, but has not been linked to instances of clinically apparent acute liver injury.|Dabigatran is a direct inhibitor of thrombin and anticoagulant which is used for prevention of stroke and venous embolism in patients with chronic atrial fibrillation. Dabigatran therapy has been associated with a low rate of serum enzyme elevations and rare instances of liver enzyme elevations and jaundice.

Antithrombotic Agents

Benzimidazoles; beta-Alanine/analogs & derivatives|Dabigatran is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. /Included in US product label/

/BOXED WARNING/ WARNING: 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.|/BOXED WARNING/ 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 anticoagulated or to be anticoagulated.|The FDA is evaluating post-marketing reports of serious bleeding events in patients taking dabigatran etexilate mesylate (Pradaxa). Bleeding that may lead to serious or even fatal outcomes is a well-recognized complication of all anticoagulant therapies. The dabigatran drug label contains a warning about significant and sometimes fatal bleeds. In a large clinical trial (18,000 patients) comparing dabigatran and warfarin, major bleeding events occurred at similar rates with the two drugs. FDA is working to determine whether the reports of bleeding in patients taking dabigatran are occurring more commonly than would be expected, based on observations in the large clinical trial that supported the approval of dabigatran. Dabigatran is a blood thinning (anticoagulant) medication used to reduce the risk of stroke in patients with non-valvular atrial fibrillation (AF), the most common type of heart rhythm abnormality. At this time, FDA continues to believe that dabigatran provides an important health benefit when used as directed and recommends that healthcare professionals who prescribe dabigatran follow the recommendations in the approved drug label. Patients with AF should not stop taking dabigatran without talking to their healthcare professional. Stopping use of blood thinning medications can increase their risk of stroke. Strokes can lead to permanent disability and death.|Dabigatran is contraindicated in patients with: active pathological bleeding; history of a serious hypersensitivity reaction to dabigatran (e.g., anaphylactic reaction or anaphylactic shock).|For more Drug Warnings (Complete) data for Dabigatran (14 total), please visit the HSDB record page.

Endogenous factors and drugs that directly inhibit the action of THROMBIN, usually by blocking its enzymatic activity. They are distinguished from INDIRECT THROMBIN INHIBITORS, such as HEPARIN, which act by enhancing the inhibitory effects of antithrombins. (See all compounds classified as Antithrombins.)

The absolute bioavailability of dabigatran following oral administration of dabigatran etexilate is approximately 3 to 7%. Dabigatran etexilate is a substrate of the efflux transporter P-gp. After oral administration of dabigatran etexilate in healthy volunteers, Cmax occurs at 1 hour post-administration in the fasted state. Coadministration of Dabigatran with a high-fat meal delays the time to Cmax by approximately 2 hours but has no effect on the bioavailability of dabigatran; Dabigatran may be administered with or without food.|The oral bioavailability of dabigatran etexilate increases by 75% when the pellets are taken without the capsule shell compared to the intact capsule formulation. Dabigatran capsules should therefore not be broken, chewed, or opened before administration.|Dabigatran is approximately 35% bound to human plasma proteins. The red blood cell to plasma partitioning of dabigatran measured as total radioactivity is less than 0.3.|The volume of distribution of dabigatran is 50 to 70 L. Dabigatran pharmacokinetics are dose proportional after single doses of 10 to 400 mg. Given twice daily, dabigatran's accumulation factor is approximately two.|For more Absorption, Distribution and Excretion (Complete) data for Dabigatran (10 total), please visit the HSDB record page.

After oral administration, dabigatran etexilate is converted to dabigatran. The cleavage of the dabigatran etexilate by esterase-catalyzed hydrolysis to the active principal dabigatran is the predominant metabolic reaction. Dabigatran is not a substrate, inhibitor, or inducer of CYP450 enzymes. Dabigatran is subject to conjugation forming pharmacologically active acyl glucuronides. Four positional isomers, 1-O, 2-O, 3-O, and 4-O-acylglucuronide exist, and each accounts for less than 10% of total dabigatran in plasma.|The pharmacokinetics and metabolism of the direct thrombin inhibitor dabigatran (BIBR 953 ZW, beta-alanine, N-((2-(((4-(aminoiminomethyl)phenyl)amino)methyl)-1-methyl-1H-benzimidazol-5-yl)carbonyl)-N-2-pyridinyl) were studied in 10 healthy males, who received 200 mg of (14)C-dabigatran etexilate (BIBR 1048 MS, the oral prodrug of dabigatran) or an i.v. infusion of 5 mg of (14)C-dabigatran. Radioactivity was measured in plasma, urine, and feces over 1 week. The metabolite pattern was analyzed by high-performance liquid chromatography with on-line radioactivity detection, and metabolite structures were elucidated by mass spectrometry. Dabigatran etexilate was rapidly converted to dabigatran, with peak plasma dabigatran concentrations being attained after approximately 1.5 hr ...The predominant metabolic reaction was esterase-mediated hydrolysis of dabigatran etexilate to dabigatran. Phase I metabolites accounted for

The half-life of dabigatran in healthy subjects is 12 to 17 hours.

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.|... To evaluate the profibrinolytic effect of dabigatran, a new, direct thrombin inhibitor, using different in vitro models. The resistance of tissue factor-induced plasma clots to fibrinolysis by exogenous tissue-type plasminogen activator (t-PA) (turbidimetric method) was reduced by dabigatran in a concentration-dependent manner, with > or = 50% shortening of lysis time at clinically relevant concentrations (1-2 um). A similar effect was observed in the presence of low (0.1 and 1 nm) but not high (10 nm) concentrations of thrombomodulin. Acceleration of clot lysis by dabigatran was associated with a reduction in TAFI activation and thrombin generation, and was largely, although not completely, negated by an inhibitor of activated TAFI, potato tuber carboxypeptidase inhibitor. The assessment of the viscoelastic properties of clots showed that those generated in the presence of dabigatran were more permeable, were less rigid, and consisted of thicker fibers. The impact of these physical changes on fibrinolysis was investigated using a model under flow conditions, which demonstrated that dabigatran made the clots markedly more susceptible to flowing t-PA, by a mechanism that was largely TAFI-independent. Dabigatran, at clinically relevant concentrations, enhances the susceptibility of plasma clots to t-PA-induced lysis by reducing TAFI activation and by altering the clot structure. These mechanisms might contribute to the antithrombotic activity of the drug.

There is no reversal agent for dabigatran. In the event of hemorrhagic complications, initiate appropriate clinical support, discontinue treatment with dabigatran, and investigate the source of bleeding. Dabigatran is primarily excreted in the urine and shows low plasma protein binding. Therefore, dabigatran can be dialyzed with the removal of about 60% of drug over 2 to 3 hours; however, data supporting this approach are limited. Measurement of aPTT or ECT may help guide therapy.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Accidental overdose may lead to hemorrhagic complications.|/CASE REPORTS/ A 59-year-old woman with paroxysmal atrial fibrillation was started on warfarin. After 3 days, warfarin was discontinued, and the decision was made to switch to dabigatran 150 mg twice a day, which was started 2 days after the warfarin was discontinued. As treatment was being converted from warfarin to dabigatran therapy, the woman's primary care physician referred her to our anticoagulation clinic, where her point-of-care INR was 7.2. A laboratory INR performed approximately 30 minutes later was 1.7. Several repeat point-of-care INRs were elevated and discordant with the laboratory INRs. A second patient, a 52-year-old man, was started on dabigatran after an ablation procedure, as a bridge to warfarin. Approximately 16 hours after a single dose of dabigatran etexilate 150 mg, the point-of-care INR was 1.6. ...In certain clinical situations (eg, switching treatment between dabigatran and warfarin), INR testing is performed as part of routine clinical care. During the development program for dabigatran, laboratory testing of INR was performed, with INRs at therapeutic concentrations of dabigatran ranging from 1.1 to 1.7. Supratherapeutic concentrations of dabigatran elevated the INR to slightly higher levels, between 1.7 and 2.4. Even at extremely high dabigatran concentrations, the INR was generally in the range of 2.3-3.5. /the authors/ advocate laboratory INR testing with simultaneous assessment of the activated partial thromboplastin time in patients who are receiving or who have recently received dabigatran. ...|/EPIDEMIOLOGY STUDIES/ The original RE-LY (Randomized Evaluation of Long-term Anticoagulant Therapy) trial suggested a small increased risk of myocardial infarction (MI) with the use of dabigatran etexilate vs warfarin in patients with atrial fibrillation. /A/ systematic evaluation /of/ the risk of MI or acute coronary syndrome (ACS) with the use of dabigatran /was conkducted/. /Investigators/ searched PubMed, Scopus, and the Web of Science for randomized controlled trials of dabigatran that reported on MI or ACS as secondary outcomes. The fixed-effects Mantel-Haenszel (M-H) test was used to evaluate the effect of dabigatran on MI or ACS. /The authors/ expressed the associations as odds ratios (ORs) and their 95% CIs. Seven trials were selected (N = 30,514), including 2 studies of stroke prophylaxis in atrial fibrillation, 1 in acute venous thromboembolism, 1 in ACS, and 3 of short-term prophylaxis of deep venous thrombosis. Control arms included warfarin, enoxaparin, or placebo administration. Dabigatran was significantly associated with a higher risk of MI or ACS than that seen with agents used in the control group (dabigatran, 237 of 20,000 [1.19%] vs control, 83 of 10,514 [0.79%]; OR(M-H), 1.33; 95% CI, 1.03-1.71; P = 0.03). The risk of MI or ACS was similar when using revised RE-LY trial results (OR(M-H), 1.27; 95% CI, 1.00-1.61; P = 0.05) or after exclusion of short-term trials (OR(M-H), 1.33; 95% CI, 1.03-1.72; P = 0.03). Risks were not heterogeneous for all analyses (I(2) = 0%; P >/= 0.30) and were consistent using different methods and measures of association. Dabigatran is associated with an increased risk of MI or ACS in a broad spectrum of patients when tested against different controls. Clinicians should consider the potential of these serious harmful cardiovascular effects with use of dabigatran.|/OTHER TOXICITY INFORMATION/ Dabigatran increases the risk of hemorrhage and may cause serious, sometimes fatal bleeding. ... Dabigatran therapy was associated with substantially lower rates of life-threatening bleeding, intracranial bleeding, and combined major or minor bleeding compared with warfarin. However, the rate of GI bleeding, including major GI bleeding, was substantially higher with dabigatran etexilate 150 mg twice daily compared with warfarin.|/OTHER TOXICITY INFORMATION/ The FDA is evaluating post-marketing reports of serious bleeding events in patients taking dabigatran etexilate mesylate (Pradaxa). Bleeding that may lead to serious or even fatal outcomes is a well-recognized complication of all anticoagulant therapies. The dabigatran drug label contains a warning about significant and sometimes fatal bleeds. In a large clinical trial (18,000 patients) comparing dabigatran and warfarin, major bleeding events occurred at similar rates with the two drugs. FDA is working to determine whether the reports of bleeding in patients taking dabigatran are occurring more commonly than would be expected, based on observations in the large clinical trial that supported the approval of dabigatran. Dabigatran is a blood thinning (anticoagulant) medication used to reduce the risk of stroke in patients with non-valvular atrial fibrillation (AF), the most common type of heart rhythm abnormality. At this time, FDA continues to believe that dabigatran provides an important health benefit when used as directed and recommends that healthcare professionals who prescribe dabigatran follow the recommendations in the approved drug label. Patients with AF should not stop taking dabigatran without talking to their healthcare professional. Stopping use of blood thinning medications can increase their risk of stroke. Strokes can lead to permanent disability and death.

BIBR 1048

Table: Dabigatran Etexilate Mesylate [Table#8060]