Eptifibatide
FDA Drug Information • Also known as: Eptifibatide
- Brand Names
- Eptifibatide
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION Eptifibatide is a cyclic heptapeptide containing 6 amino acids and 1 mercaptopropionyl (des-amino cysteinyl) residue. An interchain disulfide bridge is formed between the cysteine amide and the mercaptopropionyl moieties. Chemically it is N 6 -(aminoiminomethyl)-N 2 -(3-mercapto-1-oxopropyl)-L-lysylglycyl-L-α-aspartyl-L-tryptophyl-L-prolyl-L-cysteinamide, cyclic (1→6)-disulfide. Eptifibatide binds to the platelet receptor glycoprotein (GP) IIb/IIIa of human platelets and inhibits platelet aggregation. The eptifibatide peptide is produced by solution-phase peptide synthesis, and is purified by preparative reverse-phase liquid chromatography and lyophilized. The structural formula is: Eptifibatide Injection is a clear, colorless, sterile, non-pyrogenic solution for intravenous (IV) use with an empirical formula of C 35 H 49 N 11 O 9 S 2 and a molecular weight of 831.96. Each 10 mL vial contains 2 mg/mL of eptifibatide injection and each 100 mL vial contains 0.75 mg/mL of eptifibatide injection. Each vial of either size also contains 5.25 mg/mL citric acid and sodium hydroxide to adjust the pH to 5.35. structural formula
What Is Eptifibatide Used For?
1 INDICATIONS AND USAGE Eptifibatide injection is a platelet aggregation inhibitor indicated for: Treatment of acute coronary syndrome (ACS) managed medically or with percutaneous coronary intervention (PCI) ( 1.1 ) Treatment of patients undergoing PCI (including intracoronary stenting) ( 1.2 ) 1.1 Acute Coronary Syndrome (ACS) Eptifibatide injection 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). 1.2 Percutaneous Coronary Intervention (PCI) Eptifibatide injection is indicated to decrease the rate of a combined endpoint of death, new MI, or need for urgent intervention in patients undergoing PCI, including those undergoing intracoronary stenting [see Clinical Studies ( 14.1 , 14.2 )] .
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Before infusion of eptifibatide injection, the following laboratory tests should be performed to identify pre-existing hemostatic abnormalities: hematocrit or hemoglobin, platelet count, serum creatinine, and PT/aPTT. In patients undergoing PCI, the activated clotting time (ACT) should also be measured. The activated partial thromboplastin time (aPTT) should be maintained between 50 and 70 seconds unless PCI is to be performed. In patients treated with heparin, bleeding can be minimized by close monitoring of the aPTT and ACT. ACS or PCI: 180 mcg/kg IV bolus as soon as possible after diagnosis followed by infusion at 2 mcg/kg/min. ( 2.1 , 2.2 ) PCI: Add a second 180 mcg/kg bolus at 10 minutes. ( 2.2 ) In patients with creatinine clearance less than 50 mL/min, reduce the infusion to 1 mcg/kg/min. 2.1 , 2.2 , 2.3 ) 2.1 Dosage in Acute Coronary Syndrome (ACS) Indication Normal Renal Function Creatinine Clearance less than 50 mL/min Patients with ACS 180 mcg/kg intravenous (IV) bolus as soon as possible after diagnosis, followed by continuous infusion of 2 mcg/kg/min 180 mcg/kg IV bolus as soon as possible after diagnosis, followed by continuous infusion of 1 mcg/kg/min Infusion should continue until hospital discharge or initiation of coronary artery bypass graft surgery (CABG), up to 72 hours. If a patient is to undergo PCI, the infusion should be continued until hospital discharge or for up to 18 to 24 hours after the procedure, whichever comes first, allowing for up to 96 hours of therapy. Aspirin, 160 to 325 mg, should be given daily. Eptifibatide injection should be given concomitantly with heparin dosed to achieve the following parameters: During Medical Management : Target aPTT 50 to 70 seconds If weight greater than or equal to 70 kg, 5000-unit bolus followed by infusion of 1000 units/h. If weight less than 70 kg, 60-units/kg bolus followed by infusion of 12 units/kg/h. During PCI : Target ACT 200 to 300 seconds If heparin is initiated prior to PCI, additional boluses during PCI to maintain an ACT target of 200 to 300 seconds. Heparin infusion after the PCI is discouraged. 2.2 Dosage in Percutaneous Coronary Intervention (PCI) Indication Normal Renal Function Creatinine Clearance less than 50 mL/min Patients with PCI 180 mcg/kg IV bolus immediately before PCI followed by continuous infusion of 2 mcg/kg/min and a second bolus of 180 mcg/kg (given 10 minutes after the first bolus) 180 mcg/kg IV bolus immediately before PCI followed by continuous infusion of 1 mcg/kg/min and a second bolus of 180 mcg/kg (given 10 minutes after the first bolus) Infusion should be continued until hospital discharge, or for up to 18 to 24 hours, whichever comes first. A minimum of 12 hours of infusion is recommended. In patients who undergo CABG surgery, eptifibatide infusion should be discontinued prior to surgery. Aspirin, 160 to 325 mg, should be given 1 to 24 hours prior to PCI and daily thereafter. Eptifibatide injection should be...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reaction is also discussed elsewhere in the labeling: Bleeding [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] Bleeding and hypotension are the most commonly reported adverse reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Slate Run Pharmaceuticals, LLC at 1-888-341-9214 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 16,782 patients were treated in the Phase III clinical trials (PURSUIT, ESPRIT, and IMPACT II) [see Clinical Studies ( 14 )] . These 16,782 patients had a mean age of 62 years (range: 20-94 years). Eighty-nine percent of the patients were Caucasian, with the remainder being predominantly Black (5%) and Hispanic (5%). Sixty-eight percent were men. Because of the different regimens used in PURSUIT, IMPACT II, and ESPRIT, data from the 3 studies were not pooled. Bleeding and hypotension were the most commonly reported adverse reactions (incidence ≥5% and greater than placebo) in the eptifibatide injection controlled clinical trial database. Bleeding The incidence of bleeding and transfusions in the PURSUIT and ESPRIT studies are shown in Table 2 . Bleeding was classified as major or minor by the criteria of the TIMI study group. Major bleeding consisted of intracranial hemorrhage and other bleeding that led to decreases in hemoglobin greater than 5 g/dL. Minor bleeding included spontaneous gross hematuria, spontaneous hematemesis, other observed blood loss with a hemoglobin decrease of more than 3 g/dL, and other hemoglobin decreases that were greater than 4 g/dL but less than 5 g/dL. In patients who received transfusions, the corresponding loss in hemoglobin was estimated through an adaptation of the method of Landefeld et al. Table 2. Bleeding and Transfusions in the PURSUIT and ESPRIT Studies Note: Denominator is based on patients for whom data are available. * For major and minor bleeding, patients are counted only once according to the most severe classification. † Includes transfusions of whole blood, packed red blood cells, fresh frozen plasma, cryoprecipitate, platelets, and autotransfusion during the initial hospitalization. PURSUIT (ACS) Placebo n (%) Eptifibatide Injection 180/2 n (%) Patients 4696 4679 Major bleeding* 425 (9.3%) 498 (10.8%) Minor bleeding* 347 (7.6%) 604 (13.1%) Requiring transfusions† 490 (10.4%) 601 (12.8%) ESPRIT (PCI) Placebo n (%) Eptifibatide Injection 180/2/180 n (%) Patients 1024 1040 Major bleeding* 4 (0.4%) 13 (1.3%) Minor bleeding* 18 (2%) 29 (3%) Requiring transfusions† 11 (1.1%) 16 (1.5%) The majority of major bleeding reactions in the ESPRIT study occurred at the vascular access site (1 and 8 patients, or 0.1% and 0.8% in the placebo and eptifibatide injection groups, respectively). Bleeding at “other” locations occurred in 0.2% and 0.4% of patients, respectively. In the PURSUIT study, the greatest increase in major bleeding in eptifibatide-treated patients compared to placebo-treated patients was also associated with bleeding at the femoral artery access site (2.8% versus 1.3%). Oropharyngeal (primarily gingival), genitourinary, gastrointestinal, and retroperitoneal bleeding were also seen more commonly in eptifibatide-treated patients compared to placebo-treated patients. Among patients experiencing a major bleed in the IMPACT II study, an increase in bleeding on eptifibatide injection versus placebo was observed only for the femoral artery access site (3.2% versus 2.8%). Table 3 displays the incidence of TIMI major bleeding according to the cardiac procedures carried out in the PURSUIT study. The most common bleeding complications were related to cardiac revascularization...
Drug Interactions
7 DRUG INTERACTIONS Coadministration of antiplatelet agents, thrombolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. Avoid concomitant use with other glycoprotein (GP) IIb/IIIa inhibitors. ( 7.1 ) 7.1 Use of Thrombolytics, Anticoagulants, and Other Antiplatelet Agents Coadministration of antiplatelet agents, thrombolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. Concomitant treatment with other inhibitors of platelet receptor GP IIb/IIIa should be avoided.
Contraindications
4 CONTRAINDICATIONS Treatment with eptifibatide injection is contraindicated in patients with: A history of bleeding diathesis, or evidence of active abnormal bleeding within the previous 30 days Severe hypertension (systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg) not adequately controlled on antihypertensive therapy Major surgery within the preceding 6 weeks History of stroke within 30 days or any history of hemorrhagic stroke Current or planned administration of another parenteral GP IIb/IIIa inhibitor Dependency on renal dialysis Hypersensitivity to eptifibatide injection or any component of the product (hypersensitivity reactions that occurred included anaphylaxis and urticaria). Bleeding diathesis or bleeding within the previous 30 days. ( 4 ) Severe uncontrolled hypertension. ( 4 ) Major surgery within the preceding 6 weeks. ( 4 ) Stroke within 30 days or any history of hemorrhagic stroke. ( 4 ) Coadministration of another parenteral GP IIb/IIIa inhibitor. ( 4 ) Dependency on renal dialysis. ( 4 ) Known hypersensitivity to any component of the product. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data on eptifibatide use in pregnant women from published literature and the pharmacovigilance database are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Untreated myocardial infarction can be fatal to the pregnant woman and fetus [see Clinical Considerations ] . In animal reproduction studies, there was no evidence of adverse developmental effects when eptifibatide was administered intravenously to pregnant rats and rabbits at approximately 4 times the recommended maximum daily human dose. 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 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk: Myocardial infarction is a medical emergency in pregnancy which can be fatal to the pregnant woman and fetus if left untreated. Therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of eptifibatide injection on the fetus. Data Animal Data: Embryo-fetal development studies have been performed by continuous intravenous infusion of eptifibatide in pregnant rats during the period of organogenesis at total daily doses of up to 72 mg/kg/day (about 4 times the recommended maximum daily human dose on a body surface area basis) and in pregnant rabbits during the period of organogenesis at total daily doses of up to 36 mg/kg/day (also about 4 times the recommended maximum daily human dose on a body surface area basis). These studies revealed no evidence of harm to the fetus due to eptifibatide.
Overdosage
10 OVERDOSAGE There has been only limited experience with overdosage of eptifibatide injection. There were 8 patients in the IMPACT II study, 9 patients in the PURSUIT study, and no patients in the ESPRIT study who received bolus doses and/or infusion doses more than double those called for in the protocols. None of these patients experienced an intracranial bleed or other major bleeding. Eptifibatide was not lethal to rats, rabbits, or monkeys when administered by continuous intravenous infusion for 90 minutes at a total dose of 45 mg/kg (about 2 to 5 times the recommended maximum daily human dose on a body surface area basis). Symptoms of acute toxicity were loss of righting reflex, dyspnea, ptosis, and decreased muscle tone in rabbits and petechial hemorrhages in the femoral and abdominal areas of monkeys. From in vitro studies, eptifibatide is not extensively bound to plasma proteins and thus may be cleared from plasma by dialysis.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Eptifibatide injection is supplied as a sterile solution in 10 mL vials containing 20 mg of eptifibatide (NDC 70436-026-80) and 100 mL vials containing 75 mg of eptifibatide (NDC 70436-027-80). 16.2 Storage Vials should be stored refrigerated at 2° to 8°C (36° to 46°F). Vials may be transferred to room temperature storage* for a period not to exceed 2 months. Upon transfer, vial cartons must be marked by the dispensing pharmacist with a “DISCARD BY” date (2 months from the transfer date or the labeled expiration date, whichever comes first). Protect from light until administration. *Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.