Integril0.75 mg/ml

Integril is a glycoprotein (GP) IIb/IIIa receptor antagonist (antiplatelet agent) administered intravenously in a hospital setting. Its FDA-approved indications include:

• Acute coronary syndrome (ACS) (unstable angina/non-ST-elevation myocardial infarction): established, FDA-approved use, in patients managed medically and in those undergoing percutaneous coronary intervention (PCI), to reduce the rate of the combined endpoint of death or new myocardial infarction.
• Percutaneous coronary intervention (PCI), including intracoronary stenting: established, FDA-approved use to reduce the rate of acute ischemic complications in patients undergoing the procedure.

Integril is used as an adjunct to standard therapy, including aspirin and heparin (unfractionated or low-molecular-weight), and is not intended as stand-alone treatment. It is administered only under continuous hospital, cardiac catheterization laboratory, or coronary care unit monitoring and is not an outpatient or self-administered medication.

Each mL of Eptifibatide injection contains Eptifibatide as the active pharmaceutical ingredient, supplied as a sterile, ready-to-use, preservative-free intravenous solution (commonly available as 0.75 mg/mL and 2 mg/mL strength vials).

Integril is a synthetic cyclic heptapeptide derived from a protein found in the venom of the southeastern pygmy rattlesnake (Sistrurus miliarius barbouri). It belongs to the glycoprotein IIb/IIIa receptor antagonist class of antiplatelet agents and is administered only by intravenous infusion in a hospital or cardiac catheterization laboratory setting for acute coronary syndrome and percutaneous coronary intervention.

Integril belongs to the therapeutic class of glycoprotein IIb/IIIa receptor antagonists (antiplatelet agents), used in the management of acute coronary syndromes and during percutaneous coronary intervention.

Eptifibatide is a reversible antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. By binding to this receptor, Eptifibatide blocks the binding of fibrinogen, von Willebrand factor, and other adhesive ligands, thereby inhibiting the final common pathway of platelet aggregation regardless of the initiating stimulus.

Onset of platelet inhibition is rapid following intravenous bolus administration, and platelet function generally recovers within 4-8 hours after discontinuation of the infusion. Eptifibatide is eliminated primarily by renal excretion, and its clearance is reduced in patients with renal impairment.

Integril is given only by intravenous bolus injection followed by continuous intravenous infusion, using an infusion pump for accurate dosing, in a hospital or cardiac catheterization laboratory setting with continuous monitoring. It should be visually inspected for particulate matter and discoloration before use and should not be mixed in the same IV line with other medications unless compatibility has been established. It is typically administered together with aspirin and heparin unless contraindicated.

Integril increases the risk of bleeding when used with other agents that affect hemostasis. Key interactions include:

• Anticoagulants (e.g., heparin, warfarin) and thrombolytics: additive bleeding risk; concomitant use requires careful monitoring, and combination with full-dose thrombolytic therapy is not recommended.
• Other antiplatelet agents (e.g., aspirin, clopidogrel, NSAIDs): increased bleeding risk; these are often used concomitantly under close medical supervision as part of standard ACS/PCI management, but the combined bleeding risk must be monitored.
• Other parenteral GP IIb/IIIa inhibitors: concurrent use is contraindicated (see Contraindications).

The most common adverse effect of Integril is bleeding, ranging from minor (e.g., bruising, oozing at puncture sites, hematuria, hematemesis) to major bleeding requiring transfusion. Other adverse effects include:

• Thrombocytopenia, including rare cases of acute, profound thrombocytopenia.
• Hypotension.
• Injection or infusion site reactions.
• Rarely, hypersensitivity reactions including anaphylaxis.

Patients should be monitored closely for signs of bleeding and platelet count throughout therapy.

Pregnancy: There are no adequate and well-controlled studies of Integril in pregnant women. Integril should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; consult a physician before use in pregnancy.

Lactation: It is not known whether Integril is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse effects in nursing infants, a decision should be made whether to discontinue nursing or avoid the drug, taking into account the importance of the drug to the mother; consult a physician.

Bleeding risk: Integril increases the risk of bleeding, particularly at arterial access sites. Use the lowest effective anticoagulant dose, minimize arterial and venous punctures, and avoid intramuscular injections, urinary catheters, nasogastric tubes, and other invasive procedures where possible during therapy.

Thrombocytopenia: Monitor platelet counts before treatment and periodically during infusion; discontinue immediately if acute, profound thrombocytopenia or a platelet count below a defined safe threshold is confirmed.

Renal impairment: Requires infusion rate reduction (see Dosage and Administration); contraindicated in dialysis-dependent patients (see Contraindications).

Hypersensitivity: Anaphylaxis and other serious hypersensitivity reactions have been reported; discontinue immediately if suspected.

Use only in a hospital setting with continuous monitoring; not for outpatient or self-administration.

Overdose of Integril may increase the risk of bleeding complications. There is no specific antidote. If overdose is suspected, discontinue the infusion immediately and seek immediate medical attention; management is supportive and may include platelet transfusion if clinically significant bleeding occurs. Contact a physician or emergency medical services promptly.

Store Integril injection vials refrigerated at 2°C to 8°C (36°F to 46°F). Protect from light and do not freeze. Do not use beyond the expiration date. Keep out of reach of children. Discard any unused portion, and do not use if particulate matter or discoloration is observed. As this is a hospital-administered injectable, storage and handling are managed by healthcare facility staff.

Renal impairment: Reduce the continuous infusion rate to 1 mcg/kg/min if creatinine clearance is below 50 mL/min; contraindicated in dialysis-dependent patients (see Contraindications).

Hepatic impairment: No specific dosage recommendations are established; use with caution given the role of the liver in synthesizing hemostatic factors.

Elderly: No dosage adjustment based on age alone is required, but elderly patients may be at increased risk of bleeding; use with caution.

Pediatric patients: Safety and efficacy have not been established.

Pregnancy and lactation: See Pregnancy and Lactation section.

For acute coronary syndrome, Integril is continued until hospital discharge or initiation of CABG surgery, for up to 72 hours (up to 96 hours total if PCI is performed during therapy). For PCI, the infusion is continued for 18-24 hours after the procedure. Duration is determined by the treating physician based on clinical course, bleeding risk, and procedural outcome.

Glycoprotein IIb/IIIa receptor antagonist; antiplatelet agent.

Eptifibatide reversibly binds to the platelet glycoprotein IIb/IIIa receptor, preventing fibrinogen, von Willebrand factor, and other adhesive ligands from binding and cross-linking platelets, thereby inhibiting platelet aggregation independent of the activating stimulus.

B

Safety and efficacy of Integril have not been established in pediatric patients. Use in children is not recommended outside specialized clinical settings, and should be considered only under direct pediatric cardiology or hospital specialist supervision.