Eptifibatide

831.96

831.315613

1312995-182-4

DTXSID7046673

377 Ų

log Kow = -4.33 (est)

1.6±0.1 g/cm3

1.735

In water, 1108 mg/L at 25 °C (est)

Eptifibatide should be refrigerated at between 2-8 °C and protected from light until administration.|Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature -20 °C. Store with desiccant. /Eptifibatide acetate/

1.78X10-40 mm Hg at 25 °C (est)

Henry's Law constant = 9.88X10-34 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 6.79X10-10 cu cm/molec-sec at 25 °C (est)

Commercially available eptifibatide injection has an expiration date of 24 months following the date of manufacture when stored as directed. The injection may be transferred to room temperature storage (15-30 °C) for a period not to exceed 2 months. When stored at room temperature, the injection container should be marked to indicate that any unused vials should be discarded after 2 months or by the manufacturer's labeled expiration date (whichever comes first). The manufacturer states that vials of the injection that have been left unrefrigerated only for a brief period (i.e., the vial is still cool to the touch) may be returned to refrigeration without the need to alter the expiration date.|Stable under recommended storage conditions. /Eptifibatide acetate/

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.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product. /Eptifibatide acetate/

Incompatible materials: Strong oxidizing agents /Eptifibatide acetate/

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

|Danger|H370 (76.92%): Causes damage to organs [Danger Specific target organ toxicity, single exposure]|P260, P264, P270, P307+P311, P314, P321, P405, and P501|Aggregated GHS information provided by 13 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Eptifibatide acetate/|Skin protection: Handle with gloves. /Eptifibatide acetate/|Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Eptifibatide acetate/|Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Eptifibatide acetate/

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Eptifibatide acetate/|Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. /Eptifibatide acetate/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas; Environmental precautions: No special environmental precautions required; Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal. /Eptifibatide acetate/

Precautions for safe handling: Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed. /Eptifibatide acetate/|Appropriate engineering controls: General industrial hygiene practice. /Eptifibatide acetate/|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Eptifibatide acetate/|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.

IDENTIFICATION AND USE: Eptifibatide, as the drug Integrilin, is indicated to decrease the rate of a combined endpoint of death, new myocardial infarction (MI), or need for urgent intervention in patients undergoing percutaneous coronary intervention (PCI), including those undergoing intracoronary stenting. HUMAN EXPOSURE AND TOXICITY: Limited information is available on the acute toxicity of eptifibatide. In general, overdosage of eptifibatide in humans may be expected to produce effects that are extensions of the pharmacologic effects of the drug, predominantly bleeding. There have been cases of eptifibatide associated thrombocytopenia, which reinforces the importance of platelet count monitoring after therapy with this agent. Eptifibatide was not genotoxic in the human lymphocyte chromosome aberrations test. ANIMAL STUDIES: Single dose toxicity studies were conducted in rats, rabbits and monkeys; doses up to 500 ug/kg/minute administered by continuous intravenous infusion for 90 minutes did not cause mortality and were well-tolerated by all species. In rabbits, a dose-dependent decrease in platelet counts of the 50 and 500 ug/kg/minute (for 90 minutes)-dosed females was attributed to administration of eptifibatide. Findings in the monkeys were limited to petechial hemorrhages in the femoral and/or abdominal regions, which lasted for one to three days. Three out of five monkeys died or were sacrificed during the study due to contusions, excessive bleeding and/or petechial hemorrhages, which resulted in anemia. Total protein albumin and globulin values were reduced in all monkeys. At necropsy, focal hemorrhages in various organs were observed. In a fertility study in rats, dosing with eptifibatide had no effect on the course of pregnancy. No evidence of fertility or parental toxicity nor effects upon parental reproductive performance were observed at daily doses up to 72.0 mg/kg (24 times the maximum recommended daily human dose). Eptifibatide was not genotoxic in the Ames assay at doses up to 667 ug/mL, in the mouse lymphoma cell forward mutation assay at doses up to 1,000 ug/mL, or in the mouse micronucleus test.

Concomitant use of platelet-aggregation inhibitors and an anticoagulant (particularly in high dosages) may increase the risk of hemorrhage, and careful monitoring for bleeding is necessary, especially at arterial puncture sites. Eptifibatide and concomitant heparin therapy should be discontinued immediately and appropriate therapy (e.g., protamine sulfate in patients receiving heparin) instituted as necessary if serious bleeding occurs (e.g., bleeding not controlled by pressure). In healthy individuals, enoxaparin sodium (1 mg/kg subcutaneously every 12 hours for 4 doses) did not alter the pharmacokinetics or pharmacodynamics (platelet aggregation) of eptifibatide. The manufacturer states that caution should be employed when using eptifibatide with oral anticoagulants.|Eptifibatide has been administered concomitantly with thrombolytic agents (e.g., alteplase, streptokinase, tenecteplase) in a limited number of patients with acute myocardial infarction to reduce the risk of reocclusion of the infarct-related artery. Some clinicians suggest that use of short-acting platelet-aggregation inhibitors such as eptifibatide concomitantly with thrombolytic therapy may provide optimal benefit while minimizing the risk of bleeding However, use after thrombolysis of drugs that affect platelet function may increase the risk of bleeding complications, including those requiring blood transfusions, associated with thrombolytic therapy and has not been shown to be unequivocally effective to date; therefore, use of eptifibatide with thrombolytic therapy should be considered investigational and should be undertaken with caution.|Limited data from preclinical and clinical studies in patients receiving eptifibatide (0.5 mcg/kg per minute by IV infusion) alone or concomitantly with aspirin, heparin, or both drugs suggest no substantial pharmacokinetic or pharmacodynamic interactions (e.g., additive effects on platelet-aggregation inhibition) between eptifibatide and aspirin. While coadministration of eptifibatide and aspirin resulted in up to a fivefold increase in bleeding time compared with baseline values, similar increases in bleeding time were observed with aspirin and placebo. Nevertheless, since eptifibatide inhibits platelet aggregation, caution should be observed when the drug is used with other drugs that affect hemostasis, including thrombolytic agents, oral anticoagulants, nonsteroidal anti-inflammatory agents (NSAIAs), or dipyridamole. However, clopidogrel or ticlopidine was used routinely with eptifibatide in a large clinical, multicenter study (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT)) in patients undergoing coronary artery stent placement. To minimize potentially additive pharmacologic effects, the manufacturer of eptifibatide states that concomitant therapy with other platelet glycoprotein (GP IIb/IIIa)-receptor inhibitors (e.g., abciximab, tirofiban) should be avoided.

Because eptifibatide increases the risk of bleeding, the drug is contraindicated in patients with a history of bleeding diathesis or active abnormal bleeding (e.g., elevated hemostatic indices, recent noncompressible vascular punctures GI or genitourinary bleeding) within the previous 30 days. ... Eptifibatide also is contraindicated in patients with severe uncontrolled hypertension (systolic blood pressure exceeding 200 mm Hg or diastolic blood pressure exceeding 110 mm Hg with antihypertensive therapy); recent (within 6 weeks) major surgery; history of stroke within 30 days or any history of hemorrhagic stroke; current or planned therapy with another GP IIb/IIIa-receptor inhibitor; and patients receiving renal dialysis.

Eptifibate is present in the venom of the southeastern pygmey rattlesnake)(1); (Sistrurus miliarius; Viperidae)(2).

Platelet Aggregation 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. Eptifibatide is included in the database.|Integrilin is indicated to decrease the rate of a combined endpoint of death or new myocardial infarction (MI) in patients with ACS (unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI)), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI).|Integrilin is indicated to decrease the rate of a combined endpoint of death, new myocardial infarction (MI), or need for urgent intervention in patients undergoing percutaneous coronary intervention (PCI), including those undergoing intracoronary stenting. /Included in US product label/|Eptifibatide has been administered concomitantly with a thrombolytic agent (e.g., alteplase, tenecteplase) in a limited number of patients to prevent coronary artery reocclusion after an acute myocardial infarction. /NOT included in US product label/

The most frequent and severe adverse effect of eptifibatide therapy is bleeding. Bleeding complications, which usually are minor and develop at vascular access (e.g., femoral puncture) sites (e.g., in patients undergoing percutaneous coronary intervention (PCI)), have been reported in 35-75% of patients receiving various dosages of eptifibatide in clinical studies. Bleeding is an extension of the pharmacologic action of eptifibatide and was classified in clinical trials principally according to criteria of the Thrombolysis in Myocardial Infarction (TIMI) study groups. Minor bleeding generally was defined as spontaneous gross hematuria or spontaneous hematemesis; observed blood loss with a decrease in hemoglobin concentration of 3-5 g/dL or a reduction in hematocrit of at least 10%; or a decrease of 4-5 g/dL or 12-15% in hemoglobin or hematocrit, respectively, with no identifiable bleeding site. Major bleeding was defined as intracranial hemorrhage or overt bleeding associated with a hemoglobin or hematocrit decrease of at least 5 g/dL or at least 15%, respectively.|Because eptifibatide increases the risk of bleeding, the drug is contraindicated in patients with a history of bleeding diathesis or active abnormal bleeding (e.g., elevated hemostatic indices, recent noncompressible vascular punctures GI or genitourinary bleeding) within the previous 30 days. A low hematocrit value (less than 30%) at baseline could represent recent undetected bleeding, and patients with such values may not be able to tolerate additional bleeding episodes; eptifibatide should not be used in these patients. Eptifibatide also is contraindicated in patients with severe uncontrolled hypertension (systolic blood pressure exceeding 200 mm Hg or diastolic blood pressure exceeding 110 mm Hg with antihypertensive therapy); recent (within 6 weeks) major surgery; history of stroke within 30 days or any history of hemorrhagic stroke; current or planned therapy with another GP IIb/IIIa-receptor inhibitor; and patients receiving renal dialysis. No data are available on the use of eptifibatide in patients with serum creatinine concentrations of 4 mg/dL or greater; the dosage should be reduced in patients with serum creatinine concentrations between 2-4 mg/dL.|FDA Pregnancy Risk Category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote but remains a possibility./|Safety and effectiveness of Integrilin in pediatric patients have not been studied.|For more Drug Warnings (Complete) data for Eptifibatide (15 total), please visit the HSDB record page.

/MILK/ It is not known whether eptifibatide is distributed into milk in humans.|Eptifibatide is approximately 25% bound to plasma proteins, principally (9-16%) to albumin.The volume of distribution of eptifibatide in patients with coronary artery disease is about 185-260 mL/kg and is somewhat higher (220-270 mL/kg) in healthy individuals.|Eptifibatide, a synthetic peptide inhibitor of the platelet glycoprotein IIb/IIIa receptor, has been studied as an antithrombotic agent in a variety of acute ischemic coronary syndromes. The purpose of the present study was to characterize the disposition of (14)C-eptifibatide in man after a single intravenous (i.v.) bolus dose. (14)C-Eptifibatide (approximately 50 uCi) was administered to eight healthy men as a single 135-ug/kg IV bolus. Blood, breath carbon dioxide, urine, and fecal samples were collected for up to 72 hours postdose and analyzed for radioactivity by liquid scintillation spectrometry. Plasma and urine samples were also assayed by liquid chromatography with mass spectrometry for eptifibatide and deamidated eptifibatide (DE). Mean (+/- SD) peak plasma eptifibatide concentrations of 879 +/- 251 ng/mL were achieved at the first sampling time (5 minutes), and concentrations then generally declined biexponentially, with a mean distribution half-life of 5 +/- 2.5 minutes and a mean terminal elimination half-life of 1.13 +/- 0.17 hours. Plasma eptifibatide concentrations and radioactivity declined in parallel, with most of the radioactivity (82.4%) attributed to eptifibatide. A total of approximately 73% of administered radioactivity was recovered in the 72-hour period following (14)C-eptifibatide dosing. The primary route of elimination was urinary (98% of the total recovered radioactivity), whereas fecal (1.5%) and breath (0.8%) excretion was small. Eptifibatide is cleared by both renal and nonrenal mechanisms, with renal clearance accounting for approximately 40% of total body clearance. Within the first 24 hours, the drug is primarily excreted in the urine as unmodified eptifibatide (34%), DE (19%), and more polar metabolites (13%).|Plasma clearance of eptifibatide is proportional to body weight and estimated creatinine clearance and inversely proportional to age. Following a single IV dose of (14)C-radiolabeled eptifibatide (135 ug/kg) in healthy men, renal clearance averaged approximately 40-50% of total body clearance. Clearance is reduced by 50% in patients with moderate to severe renal impairment (estimated Clcr less than 50 mL/minute). Total body clearance in geriatric patients with coronary artery disease is lower than that in younger adults.|For more Absorption, Distribution and Excretion (Complete) data for Eptifibatide (9 total), please visit the HSDB record page.

(14)C-eptifibatide was extensively metabolized to deamidated eptifibatide and to several polar metabolites by both rats and monkeys. The drug-derived radioactivity excreted into the bile by rats, and identified as deamidated eptifibatide, was reabsorbed from the intestinal tract and further metabolized to more polar metabolites. The plasma and urine metabolite profiles in rats and monkeys indicate that the metabolic disposition of eptifibatide is similar for the two species.|Eptifibatide is metabolized principally through deamidation to a metabolite that has approximately 41% of the platelet-aggregation inhibitory activity of the parent compound, and through formation of other more polar metabolites. Approximately 27% of a dose of eptifibatide is broken down in plasma into naturally occurring amino acids; no major non-amino acid metabolites have been detected in plasma in humans.

In Cynomolgus monkeys, plasma concentrations of (14)C-eptifibatide-derived radioactivity declined with a half life of about 12 hours following a single 2 mg/kg IV dose of (14)C-eptifibatide. Unchanged eptifibatide, which accounted for approximately 93% of total plasma (14)C at 5 min post-dose, was eliminated rapidly with a half life of 17 min.|In rats, plasma concentrations of (14)C-eptifibatide-derived radioactivity declined rapidly with a terminal phase half life of about 5 hours following a single 2 mg/kg IV dose of the radiolabeled drug. Unchanged eptifibatide declined with an apparent half life of about 8 min. Following single 2 and 20 mg/kg IV doses, the plasma concentrations of eptifibatide were dose-proportional and the half life (11 to 12 min) was dose-independent, indicating linear kinetics within the 2 to 20 mg/kg dose range.|The half-life of eptifibatide in patients with coronary artery disease averages 2.5-2.8 hours. In healthy individuals, half-life of the drug reportedly averages 0.83-2.4 hours.|... The purpose of the present study was to characterize the disposition of (14)C-eptifibatide in man after a single intravenous (IV) bolus dose. (14)C-Eptifibatide (approximately 50 uCi) was administered to eight healthy men as a single 135-ug/kg IV bolus. ... Mean (+/- SD) peak plasma eptifibatide concentrations of 879 +/- 251 ng/mL were achieved at the first sampling time (5 minutes), and concentrations then generally declined biexponentially, with a mean distribution half-life of 5 +/- 2.5 minutes and a mean terminal elimination half-life of 1.13 +/- 0.17 hours. ...

/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/

/SIGNS AND SYMPTOMS/ Limited information is available on the acute toxicity of eptifibatide. In general, overdosage of eptifibatide in humans may be expected to produce effects that are extensions of the pharmacologic and adverse effects of the drug, predominantly bleeding.|/CASE REPORTS/ Glycoprotein (GP) IIb/IIIa inhibitors reduce major adverse coronary events in patients with acute coronary syndromes undergoing percutaneous coronary interventions (PCI). Unlike the other GPIIb/IIIa inhibitors, eptifibatide is rarely associated with thrombocytopenia with only a few cases reported in the medical literature. Here we report a case of a 34-year-old man presenting with a non ST-elevation myocardial infarction (NSTEMI) who underwent primary PCI with stenting and developed stent thrombosis 5 days after the procedure. He underwent repeat PCI with readministration of eptifibatide and subsequently developed profound thrombocytopenia within 4 hr. This report adds another case of eptifibatide associated thrombocytopenia to the literature and reinforces the importance of platelet count monitoring after therapy with this agent.|/CASE REPORTS/ A 57-year-old man with a history of coronary artery disease and placement of an implantable cardioverter-defibrillator presented at our emergency room with an anterior ST-elevation myocardial infarction. Cardiac catheterization revealed an acutely occluded left main coronary artery, which was revascularized successfully with a bare-metal stent. Periprocedurally, the patient received aspirin, clopidogrel, unfractionated heparin, and eptifibatide. The patient was discharged a week later, but he returned to the emergency room the same day with recurrence of severe chest pain. Repeat cardiac catheterization revealed an acutely occluded stent, and the patient underwent repeat bare-metal stent placement and readministration of eptifibatide. On the next day, the patient's platelet count dropped acutely to less than 12,000/cu mm. A test for heparin-induced thrombocytopenia antibody was negative. After discontinuation of eptifibatide, the patient's platelet count gradually returned to normal, and he was later discharged from the hospital with no complications. Eptifibatide-induced acute thrombocytopenia is a known but rare adverse effect. We review the handful of case reports in the medical literature, with emphasis on the prevalence, observed clinical course, and recently proposed physiologic mechanisms that probably are responsible for this phenomenon.|/CASE REPORTS/ Thrombocytopenia in acute coronary syndromes (ACS) can arise from a variety of etiologies. Glycoprotein IIb/IIIa receptor antagonists have improved clinical outcomes in ACS, however, profound thrombocytopenia can occur with use of these agents. We present a case of profound thrombocytopenia due to administration of a glycoprotein IIb/IIIa receptor antagonist, eptifibatide, after percutaneous coronary intervention for an inferior ST-elevation myocardial infarction. We review the major causes and suggest an approach for diagnosis and management of thrombocytopenia in ACS.|For more Human Toxicity Excerpts (Complete) data for Eptifibatide (13 total), please visit the HSDB record page.

Injection: 20 mg of Integrilin in 10 mL (2 mg/mL), for intravenous bolus Injection: 75 mg of Integrilin in 100 mL (0.75 mg/mL), for intravenous infusion. Injection: 200 mg of Integrilin in 100 mL (2 mg/mL), for intravenous infusion.