Edoxaban

548.065

548.06

1592732-453-0

NDU3J18APO

DTXSID50197398

C96539

White to pale yellowish-white crystalline powder

B01|B01AF03|B - Blood and blood forming organs

2934999090

165

1.4

1.4±0.1 g/cm3

Crystals as monohydrate from ethanol + water. MP: 245-48 (decomposes) /Edoxaban tosylate/

1.646

In water, 93.29 mg/L at 25 °C (est)

Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: -20 °C. /Edoxaban tosylate/|Store at 20-25 °C (68-77 °F); excursions permitted to 15 deg - 30 °C (59 deg - 86 °F). /Edoxaban tosylate/

2.03X10-21 mm Hg at 25 °C (est)

6.7None

Henry's Law constant = 3.11X10-34 atm-cu m/mol at 25 °C (est)

pKa 6.7 /Edoxaban tosylate/

The solublilty decreases with increasing pH. It is slightly soluble in water, pH 3 to 5 buffer, very slightly soluble at pH 6 to 7; practically insoluble at pH 8 to 9 /Edoxaban tosylate/|Hydroxyl radical reaction rate constant = 1.55X10-12 cu cm/molec-sec at 25 °C (est)

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 edoxaban tosylate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Edoxaban tosylate/

|Warning|H373 (100%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]|P260, P314, and P501|Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory.

Skin and body protection: Choose body protection according to the amount and concentration of the dangerous substances at the work place. /Edoxaban tosylate/|Eye protection: Safety glasses with side-shields conforming to EN166. /Edoxaban tosylate/|Hand protection: Handle with gloves. For prolonged or repeated contact use protective gloves. /Edoxaban tosylate/|Respiratory protection: Where risk assessment shows air-purifying respiratory are appropriate use a dust mask type N95 (US) or type P1 (EN 143) respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Edoxaban tosylate/

Not flammable or combustible. /Edoxaban tosylate/

Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Edoxaban tosylate/

ACCIDENTAL RELEASE MEASURES. Personal precautions: Use personal protective equipment. Avoid dust formation. Avoid breathing dust. Ensure adequate ventilation. Environmental precautions: Do not let product enter drains. Methods for cleaning up: Pick up and arrange disposal without creating dust. Keep in suitable, closed containers for disposal. /Edoxaban tosylate/

Hygiene measures: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of the workday. /Edoxaban tosylate/|Precautions for safe handling: Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Edoxaban tosylate/|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|ACCIDENTAL RELEASE MEASURES. Personal precautions: Use personal protective equipment. Avoid dust formation. Avoid breathing dust. Ensure adequate ventilation. Environmental precautions: Do not let product enter drains. /Edoxaban tosylate/

Premature discontinuation of any oral anticoagulant, including edoxaban, in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If edoxaban is discontinued for reasons other than pathological bleeding or completion of a course of therapy, consider the use of another anticoagulant. Edoxaban increases the risk of potentially fatal major bleeding such as intracranial hemorrhage and gastrointestinal bleeding. Patients should be educated on how to watch for signs of major and minor bleeding and when to seek medical help. Co-administration of other anti-coagulants, anti-platelets, or thrombolytics may increase the risk of bleeding and should therefore be avoided.|IDENTIFICATION AND USE: Edoxaban is a white to pale yellowish-white crystalline powder. It is used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. It is also used for the treatment of deep vein thrombosis (DVT) and pulmonary embolism following 5 to 10 days of initial therapy with a parenteral anticoagulant. HUMAN STUDIES: Overdose of the drug increases the risk of bleeding. Edoxaban increases the risk of hemorrhage and can cause serious, potentially fatal, bleeding. Patients should be promptly evaluated if any manifestations of blood loss occur during therapy. The drug should be discontinued if active pathological bleeding occurs. However, minor or "nuisance" bleeding is a common occurrence in patients receiving any anticoagulant and should not readily lead to treatment discontinuance. Edoxaban and its human-specific metabolite, M-4 were not genotoxic in in vitro human lymphocytes micronucleus test. ANIMAL STUDIES: Edoxaban was not carcinogenic when administered daily to mice and rats by oral gavage for up to 104 weeks. Edoxaban showed no effects on fertility and early embryonic development in rats at doses of up to 1000 mg/kg/day. In a rat pre- and post-natal developmental study, edoxaban was administered orally during the period of organogenesis and through lactation day 20 at doses up to 30 mg/kg/day. Vaginal bleeding in pregnant rats and delayed avoidance response (a learning test) in female offspring were seen at 30 mg/kg/day. Embryo-fetal development studies were conducted in pregnant rats and rabbits during the period of organogenesis. In rats, no malformation was seen when edoxaban was administered orally at doses up to 300 mg/kg/day. Increased post-implantation loss occurred at 300 mg/kg/day, but this effect may be secondary to the maternal vaginal hemorrhage seen at this dose in rats. In rabbits, no malformation was seen at doses up to 600 mg/kg/day. Embryo-fetal toxicities occurred at maternally toxic doses, and included absent or small fetal gallbladder at 600 mg/kg/day, and increased post-implantation loss, increased spontaneous abortion, and decreased live fetuses and fetal weight at doses equal to or greater than 200 mg/kg/day. Edoxaban and its human-specific metabolite, M-4, were genotoxic in in vitro chromosomal aberration tests but were not genotoxic in the in vitro bacterial reverse mutation (Ames test), in in vivo rat bone marrow micronucleus test, in in vivo rat liver micronucleus test, and in in vivo unscheduled DNA synthesis tests.

Edoxaban is associated with serum aminotransferase elevations ≥3 times the upper limit of normal in 2% to 5% of treated patients. This rate is similar or lower than rates with warfarin or comparator arms. The elevations are generally transient and not associated with symptoms or jaundice. In premarketing studies, no instances of clinically apparent liver injury were reported, but experience in large numbers of patients treated for extend periods of time is limited.

Edoxaban, an oral direct factor Xa inhibitor, is in development for thromboprophylaxis, including prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). P-glycoprotein (P-gp), an efflux transporter, modulates absorption and excretion of xenobiotics. Edoxaban is a P-gp substrate, and several cardiovascular (CV) drugs have the potential to inhibit P-gp and increase drug exposure. /The objective of the study was/ to assess the potential pharmacokinetic interactions of edoxaban and 6 cardiovascular drugs used in the management of AF and known P-gp substrates/inhibitors. Drug-drug interaction studies with edoxaban and CV drugs with known P-gp substrate/inhibitor potential were conducted in healthy subjects. In 4 crossover, 2-period, 2-treatment studies, subjects received edoxaban 60 mg alone and coadministered with quinidine 300 mg (n = 42), verapamil 240 mg (n = 34), atorvastatin 80 mg (n = 32), or dronedarone 400 mg (n = 34). Additionally, edoxaban 60 mg alone and coadministered with amiodarone 400 mg (n = 30) or digoxin 0.25 mg (n = 48) was evaluated in a single-sequence study and 2-cohort study, respectively. Edoxaban exposure measured as area under the curve increased for concomitant administration of edoxaban with quinidine (76.7%), verapamil (52.7%), amiodarone (39.8%), and dronedarone (84.5%), and exposure measured as 24 hr concentrations for quinidine (11.8%), verapamil (29.1%), and dronedarone (157.6%) also increased. Administration of edoxaban with amiodarone decreased the 24-hr concentration for edoxaban by 25.7%. Concomitant administration with digoxin or atorvastatin had minimal effects on edoxaban exposure. Coadministration of the P-gp inhibitors quinidine, verapamil, and dronedarone increased edoxaban exposure. Modest/minimal effects were observed for amiodarone, atorvastatin, and digoxin.|The oral direct factor Xa inhibitor edoxaban is a P-glycoprotein (P-gp) substrate metabolized via carboxylesterase-1 and cytochrome P450 (CYP) 3A4/5. The effect of rifampin-induced induction of P-gp and CYP3A4/5 on transport and metabolism of edoxaban through the CYP3A4/5 pathway was investigated in a single-dose edoxaban study. This was a phase 1, open-label, two-treatment, two-period, single-sequence drug interaction study in healthy adults. All subjects received a single oral 60 mg edoxaban dose in period 1, and 7 days of 600 mg rifampin (2 x 300 mg capsules once daily) with a single oral edoxaban 60 mg dose administered concomitantly on day 7 in period 2. A 6-day washout period separated the treatments. Plasma concentrations of edoxaban and its metabolites M4 and M6 were measured, and limited assessments of pharmacodynamic markers of coagulation were performed. In total, 34 healthy subjects were enrolled; 32 completed the study. Coadministration of rifampin with edoxaban decreased edoxaban exposure but increased active metabolite exposure. Rifampin increased apparent oral clearance of edoxaban by 33% and decreased its half-life by 50%. Anticoagulant effects based on the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) with and without rifampin at early time points were maintained to a greater-than-expected degree than with edoxaban exposure alone, presumably because of an increased contribution from the active metabolites. Edoxaban was well tolerated in this healthy adult population. Rifampin reduced exposure to edoxaban while increasing exposure to its active metabolites M4 and M6. PT and aPTT at early time points did not change appreciably; however, the data should be interpreted with caution.|Verapamil increased peak plasma concentrations and systemic exposure of edoxaban by approximately 53%; pharmacokinetic parameters of verapamil were altered to only a slight extent. Dosage of edoxaban should be reduced when the drug is administered concomitantly with verapamil in patients with venous thromboembolism.|Quinidine increased peak plasma concentrations and systemic exposure of edoxaban by approximately 85 and 77%, respectively, but edoxaban did not affect pharmacokinetics of quinidine. Dosage of edoxaban should be reduced when the drug is administered concomitantly with quinidine in patients with venous thromboembolism.|For more Interactions (Complete) data for Edoxaban (19 total), please visit the HSDB record page.

Edoxaban tosylate should not be used in patients with nonvalvular atrial fibrillation who have a creatinine clearance exceeding 95 mL/minute; the manufacturer states that alternative anticoagulants should be used in such patients. Reduced antithrombotic efficacy was observed in the principal efficacy trial of the drug (ENGAGE AF-TIMI 48) in patients with nonvalvular atrial fibrillation who had a creatinine clearance exceeding 95 mL/minute. In particular, the rate of ischemic stroke was substantially increased in such patients who were receiving edoxaban 60 mg daily compared with warfarin-treated patients who had a similar level of renal function.|Safety and efficacy of edoxaban have not been evaluated in patients with mechanical heart valves or moderate to severe mitral stenosis; use of the drug is not recommended in such patients.|Savaysa is contraindicated in patients with: Active pathological bleeding.

In vitro plasma protein binding is ~55%.

Edoxaban is indicated for reducing the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF). However, it should not be used in patients with creatinine clearance (CrCL) > 95 mL/min because of increased risk of ischemic stroke compared to warfarin at the highest dose studied (60 mg). It is also indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5-10 days of initial therapy with a parenteral anticoagulant.|FDA Label|Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA)., , Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.,|Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA).Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.

Edoxaban is an oral, small molecule inhibitor of factor Xa which is used as an anticoagulant to decrease the risk of venous thromboses, systemic embolization and stroke in patients with atrial fibrillation, and as treatment of deep vein thrombosis and pulmonary embolism to prevent thrombotic complications. Edoxaban has been linked to a low rate of serum aminotransferase elevations during therapy, but has not been implicated in cases of clinically apparent acute liver injury.

Anticoagulants

Factor Xa Inhibitors|/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Edoxaban is included in the database.|Savaysa is indicated to reduce the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF). /Included in US product label/|Savaysa is indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5 to 10 days of initial therapy with a parenteral anticoagulant. /Included in US product label/|For more Therapeutic Uses (Complete) data for Edoxaban (7 total), please visit the HSDB record page.

/BOXED WARNING/ REDUCED EFFICACY IN NONVALVULAR ATRIAL FIBRILLATION PATIENTS WITH CRCL > 95 ML/MIN. Savaysa should not be used in patients with CrCL > 95 mL/min. In the ENGAGE AF-TIMI 48 study, nonvalvular atrial fibrillation patients with CrCL > 95 mL/min had an increased rate of ischemic stroke with Savaysa 60 mg once daily compared to patients treated with warfarin. In these patients another anticoagulant should be used.|/BOXED WARNING/ PREMATURE DISCONTINUATION OF SAVAYSA INCREASES THE RISK OF ISCHEMIC EVENTS. Premature discontinuation of any oral anticoagulant in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If Savaysa is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant as described in the transition guidance.|/BOXED WARNING/ SPINAL/EPIDURAL HEMATOMA. Epidural or spinal hematomas may occur in patients treated with Savaysa 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 nonsteroidal 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 Savaysa and neuraxial procedures is not known. Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessar. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.|Safety and efficacy of edoxaban have not been evaluated in patients with mechanical heart valves or moderate to severe mitral stenosis; use of the drug is not recommended in such patients.|For more Drug Warnings (Complete) data for Edoxaban (18 total), please visit the HSDB record page.

Administration of edoxaban results in prolongation of clotting time tests such as aPTT (activated partial thromboplastin time), PT (prothrombin time), and INR (international normalized ratio).

Endogenous factors and drugs that inhibit or block the activity of FACTOR XA. (See all compounds classified as Factor Xa Inhibitors.)

Following oral administration, peak plasma edoxaban concentrations are observed within 1-2 hours. Absolute bioavailability is 62%.|Edoxaban is eliminated primarily as unchanged drug in urine. Renal clearance (11 L/hour) accounts for approximately 50% of the total clearance of edoxaban (22 L/hour). Metabolism and biliary/intestinal excretion account for the remaining clearance.|The steady state volume of distribution is 107 L.|22 L/hr|/MILK/ There are no data on the presence of edoxaban in human milk ... . Edoxaban was present in rat milk. ...|Disposition is biphasic. The steady-state volume of distribution (Vdss) is 107 (19.9) L (mean (SD)). In vitro plasma protein binding is approximately 55%. There is no clinically relevant accumulation of edoxaban (accumulation ratio 1.14) with once daily dosing.|Administration of a crushed 60 mg tablet, either mixed into applesauce or suspended in water and given through a nasogastric tube, showed similar exposure compared to administration of an intact tablet.|Edoxaban is eliminated primarily as unchanged drug in the urine. Renal clearance (11 L/hour) accounts for approximately 50% of the total clearance of edoxaban (22 L/hour). Metabolism and biliary/intestinal excretion account for the remaining clearance.|Following oral administration, peak plasma edoxaban concentrations are observed within 1-2 hours. Absolute bioavailability is 62%. Food does not affect total systemic exposure to edoxaban. Savaysa was administered with or without food in the ENGAGE AF-TIMI 48 and Hokusai VTE trials.

Edoxaban is not extensively metabolized by CYP3A4 resulting in minimal drug-drug interactions. However, it does interact with drugs that inhibit p-gp (p-glycoprotein), which is used to transport edoxaban across the intestinal wall. Unchanged edoxaban is the predominant form in plasma. There is minimal metabolism via hydrolysis (mediated by carboxylesterase 1), conjugation, and oxidation by CYP3A4. The predominant metabolite M-4, formed by hydrolysis, is human-specific and active and reaches less than 10% of the exposure of the parent compound in healthy subjects. Exposure to the other metabolites is less than 5% of exposure to edoxaban.|... All subjects received a single oral 60 mg edoxaban dose in period 1, and 7 days of 600 mg rifampin (2 x 300 mg capsules once daily) with a single oral edoxaban 60 mg dose administered concomitantly on day 7 in period 2. A 6-day washout period separated the treatments. Plasma concentrations of edoxaban and its metabolites M4 and M6 were measured, and limited assessments of pharmacodynamic markers of coagulation were performed. In total, 34 healthy subjects were enrolled; 32 completed the study. Coadministration of rifampin with edoxaban decreased edoxaban exposure but increased active metabolite exposure. Rifampin increased apparent oral clearance of edoxaban by 33% and decreased its half-life by 50%. Anticoagulant effects based on the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) with and without rifampin at early time points were maintained to a greater-than-expected degree than with edoxaban exposure alone, presumably because of an increased contribution from the active metabolites. Edoxaban was well tolerated in this healthy adult population. Rifampin reduced exposure to edoxaban while increasing exposure to its active metabolites M4 and M6. PT and aPTT at early time points did not change appreciably; however, the data should be interpreted with caution.|Edoxaban and its low-abundance, active metabolite M4 are substrates of P-glycoprotein (P-gp; MDR1) and organic anion transporter protein 1B1 (OATP1B1), respectively, and pharmacological inhibitors of P-gp and OATP1B1 can affect edoxaban and M4 pharmacokinetics (PK). In this integrated pharmacogenomic analysis, genotype and concentration-time data from 458 healthy volunteers in 14 completed phase 1 studies were pooled to examine the impact on edoxaban PK parameters of allelic variants of ABCB1 (rs1045642: C3435T) and SLCO1B1 (rs4149056: T521C), which encode for P-gp and OATP1B1. Although some pharmacologic inhibitors of P-gp and OATP1B1 increase edoxaban exposure, neither the ABCB1 C3435T nor the SLCO1B1 T521C polymorphism affected edoxaban PK. A slight elevation in M4 exposure was observed among SLCO1B1 C-allele carriers; however, this elevation is unlikely to be clinically significant as plasma M4 concentrations comprise <10% of total edoxaban levels.|The predominant metabolite M-4, formed by hydrolysis, is human-specific and active and reaches less than 10% of the exposure of the parent compound in healthy subjects. Exposure to the other metabolites is less than 5% of exposure to edoxaban.|Unchanged edoxaban is the predominant form in plasma. There is minimal metabolism via hydrolysis (mediated by carboxylesterase 1), conjugation, and oxidation by CYP3A4.

The terminal elimination half-life of edoxaban following oral administration is 10 to 14 hours.

Edoxaban is a selective inhibitor of factor Xa, a serine endopeptidase of the clotting cascade required for cleavage of prothrombin into thrombin.|Edoxaban tosylate monohydrate, an oral, direct activated factor X (Xa) inhibitor, is an anticoagulant. Factor Xa plays a central role in the blood coagulation cascade by serving as the convergence point for the intrinsic and extrinsic pathways; inhibition of coagulation factor Xa by edoxaban prevents conversion of prothrombin to thrombin and subsequent thrombus formation. The drug binds directly and selectively to factor Xa without the need for a cofactor (e.g., antithrombin III), and inhibits both free and prothrombinase-bound factor Xa as well as thrombin-induced platelet aggregation.

/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 TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) 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/|Emergency and supportive measures. 1. If significant bleeding occurs, attempt to identify the source of bleeding and provide local control or hemostasis if possible. Give intravenous volume replacement as needed and closely monitor hemodynamics. obtain immediate neurosurgical consult if intracranial bleeding is suspected. 2. Administer specific antidote as directed. 3. For severe or life-threatening bleeding, use a specific reversal agent ... or consider one of the prothrombin complex concentrates (PCCs) or activated PPC (APPC). for dabigatran, APCC is the preferred agent, for factor Xa inhibitors, a 4-factor PCC is preferred. The utility of these concentrates is limited by the stoichiometric ration needed to over come the effects of the newer direct anticoagulants. 4. Fresh-frozen plasma is likely of limited utility given volume constraints and sheer amount that would be required to over come drug effect, but may have a role for coagulopathies caused by dilution or DIC. 5. Consider platelet transfusion for patient son concurrent antiplatelet agents. 6. Desmopressin enhances hemostasis by increasing the release of von Willebrand factor and can be considered as a adjunct. ... 7. Packed red blood cell transfusion should be administered as indicated for blood loss. 8. Take care not to precipitate hemorrhage in severely anticoagulated patients. Proper fall precautions should be taken and invasive procedures should be avoided if possible. /Anticoagulants, newer/|For more Antidote and Emergency Treatment (Complete) data for Edoxaban (8 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ Overdose of Savaysa increases the risk of bleeding.|/SIGNS AND SYMPTOMS/ Edoxaban increases the risk of hemorrhage and can cause serious, potentially fatal, bleeding. Patients should be promptly evaluated if any manifestations of blood loss occur during therapy. The drug should be discontinued if active pathological bleeding occurs. However, minor or "nuisance" bleeding is a common occurrence in patients receiving any anticoagulant and should not readily lead to treatment discontinuance.|/CASE REPORTS/ The main adverse effect of anticoagulant therapy is bleeding, and major bleeding, including intracranial, gastrointestinal, and retroperitoneal bleeding, has been reported as an adverse effect of edoxaban, a direct oral anticoagulant (DOAC). Bleeding during systemic anticoagulation with edoxaban presents a therapeutic conundrum, because there is currently no safe or efficacious reversal agent to stop major bleeding. A 51-year-old woman had multiple traumatic injuries, including lower limb fractures. On day 8, she developed deep venous thrombosis, and edoxaban was administered orally. On day 38, she developed fungemia, which was treated with an antifungal drug. On day 43, she presented with dyspnea. Chest computed tomography scan showed bilateral diffuse ground-glass opacities in the whole lung fields. The results of the subsequent workup (i.e., serum levels of the antineutrophil cytoplasmic antibody, antinuclear antibody, and antiglomerular basement membrane antibody) and microbiological study were unremarkable. Based on these findings, her condition was diagnosed as diffuse alveolar hemorrhage (DAH) associated with edoxaban therapy. The lung opacities disappeared spontaneously after edoxaban therapy was discontinued. DAH is a dangerous complication associated with edoxaban therapy. DOACs, including edoxaban, should be prescribed with caution, especially for patients in a critical condition.|/CASE REPORTS/ Factor-Xa inhibitors like edoxaban have been shown to have comparable or superior rates of stroke and systemic embolization prevention to warfarin while exhibiting lower clinically significant bleeding rates. The authors report a case of a man who presented with delayed, recurrent intracranial hemorrhage months after successful deep brain stimulator placement for Parkinson disease while on edoxaban for atrial fibrillation. Further reports on the use of novel anticoagulants after intracranial surgery are acutely needed to help assess the true relative risk they pose.|For more Human Toxicity Excerpts (Complete) data for Edoxaban (9 total), please visit the HSDB record page.

DU-176

Table: Edoxaban Tosylate Preparations [Table#8466]

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