Eptifibatid (Solution) Instructions for Use

Marketing Authorization Holder

B-PHARM, LLC (Russia)

Manufactured By

Academician E.I. Chazov NMRC Of Cardiology Of The Ministry Of Health Of The Russian Federation, FSBI (Russia)

ATC Code

B01AC16 (Eptifibatide)

Active Substance

Eptifibatide (Rec.INN registered by WHO)

Dosage Forms

	Eptifibatide	Solution for intravenous administration 0.75 mg/1 ml: vial 100 ml 1 pc.
		Solution for intravenous administration 2 mg/1 ml: amp. 10 ml 1 pc.

Dosage Form, Packaging, and Composition

Solution for intravenous administration transparent, colorless.

Excipients : citric acid monohydrate – 5.25 mg, sodium hydroxide – q.s. to pH 5.25, water for injections – up to 1 ml.

100 ml – amber glass bottles (1) – cardboard packs.

Solution for intravenous administration transparent, colorless.

Excipients : citric acid monohydrate – 5.25 mg, sodium hydroxide – q.s. to pH 5.25, water for injections – up to 1 ml.

10 ml – ampoules of colorless glass of hydrolytic class 1 (1) – cardboard packs.

Clinical-Pharmacological Group

Antiplatelet agent

Pharmacotherapeutic Group

Antiaggregant agent

Pharmacological Action

Antiplatelet agent, a synthetic cyclic heptapeptide containing 6 amino acids and a mercaptopropionyl residue – deaminocysteinyl. An inhibitor of platelet aggregation belonging to the class of RGD (arginine-glycine-aspartate) stimulants: it suppresses platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor and other adhesive ligands to platelet glycoprotein IIb/IIIa receptors.

When administered intravenously, it causes suppression of platelet aggregation, the degree of which depends on the dose and concentration of the drug. Inhibition of platelet aggregation is reversible; 4 hours after stopping the infusion, platelet function is restored by more than 50%. It does not have a noticeable effect on prothrombin time and aPTT.

Pharmacokinetics

The pharmacokinetics of eptifibatide is linear and dose-dependent when administered as a bolus at doses from 90 to 250 mcg/kg and as an infusion at rates from 0.5 to 3 mcg/kg/min. When the drug is administered according to the recommended regimen (bolus, then infusion), its plasma concentration quickly reaches a peak, then slightly decreases and reaches equilibrium within 4-6 hours.

During coronary angioplasty, this decrease can be avoided by administering a second bolus of 180 mcg/kg 10 minutes after the first one. Plasma protein binding is 25%.

T_1/2 is 2.5 hours, clearance is 55-58 ml/kg/h and V_d is 185-260 ml/kg. In healthy individuals, the proportion of renal clearance from the total is 50%; most of it is excreted by the kidneys unchanged and in the form of metabolites. The main metabolites were not detected in human plasma.

Indications

Acute coronary syndrome (including unstable angina, acute myocardial infarction); prevention of thrombotic occlusion of the affected artery and acute ischemic complications during percutaneous transluminal coronary angioplasty (PTCA), including intracoronary stenting.

ICD codes

Dosage Regimen

Administer intravenously as a bolus injection followed by a continuous infusion. Use in combination with acetylsalicylic acid and heparin.

For Acute Coronary Syndrome, administer an intravenous bolus of 180 mcg/kg followed by a continuous infusion of 2 mcg/kg/min.

For patients undergoing Percutaneous Coronary Intervention (PCI), administer an intravenous bolus of 180 mcg/kg immediately before the procedure. Initiate a continuous infusion of 2 mcg/kg/min simultaneously. Administer a second 180 mcg/kg bolus 10 minutes after the first.

Continue the infusion until hospital discharge or for up to 72 hours. For patients undergoing PCI, continue the infusion for up to 18-24 hours post-procedure. The maximum infusion duration is 96 hours.

In patients with renal impairment (creatinine clearance less than 50 mL/min), reduce the infusion rate to 1 mcg/kg/min. Do not reduce the bolus dose.

Calculate all doses based on the patient’s actual body weight. Monitor hemoglobin, hematocrit, and platelet count prior to therapy, within 6 hours of the first bolus, and at least daily thereafter during therapy.

Discontinue eptifibatide and heparin if serious bleeding occurs or if the platelet count falls below 100,000/mm³.

Adverse Reactions

From the blood coagulation system minor bleeding (including macrohematuria) are more often observed with simultaneous use with heparin; less often – major bleeding; extremely rarely – intracranial hemorrhage; in isolated cases – fatal bleeding.

From the hematopoietic system thrombocytopenia (platelet count <100,000 cells/µl, or a decrease in their number by 50% or more from the baseline level).

Contraindications

History of hemorrhagic diathesis or significant pathological bleeding within the previous 30 days, severe arterial hypertension (systolic BP >200 mm Hg or diastolic BP >110 mm Hg) during antihypertensive therapy, major surgical interventions within the previous 6 weeks, ischemic stroke within the previous 30 days or history of hemorrhagic stroke, concurrent or planned use of another parenteral inhibitor of platelet glycoprotein IIb/IIIa receptors, need for hemodialysis due to renal failure, in patients who, according to clinical indications, require the administration of thrombolytics (in acute transmural myocardial infarction with a new pathological Q wave, ST segment elevation or left bundle branch block on ECG), lactation period (breastfeeding), children and adolescents under 18 years of age, hypersensitivity to eptifibatide.

Use in Pregnancy and Lactation

Use during pregnancy with caution and only in cases where the expected therapeutic benefit outweighs the potential risk to the fetus.

The use of eptifibatide is contraindicated during lactation (breastfeeding).

Use in Renal Impairment

Contraindication: need for hemodialysis due to renal failure, in patients who, according to clinical indications, require the administration of thrombolytics (in acute transmural myocardial infarction with a new pathological Q wave, ST segment elevation or left bundle branch block on ECG).

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Special Precautions

Eptifibatide is intended for use only in a hospital setting. Before starting treatment, all patients should be thoroughly examined to identify possible bleeding, especially women, elderly patients, and patients with low body weight, as they have the highest risk of hemorrhagic complications. The risk of bleeding is greatest at the arterial access site in patients undergoing PTCA.

It is necessary to carefully monitor possible bleeding sites (including the catheterization site); one should also be alert for possible bleeding from the gastrointestinal and genitourinary tracts, and retroperitoneal bleeding.

Caution should be exercised when used concomitantly with other drugs affecting the hemostatic system, including thrombolytics, anticoagulants, dextran, adenosine phosphate, NSAIDs, sulfinpyrazone, and antiplatelet agents.

If emergency surgery is required during treatment, the drug should be discontinued immediately. Before elective surgery, the drug should be discontinued in advance so that platelet function returns to normal.

During treatment, it is necessary to limit the number of arterial and venous punctures, avoid intramuscular injections, and the use of urinary catheters, endotracheal tubes, and nasogastric tubes. For intravenous access, veins that cannot be compressed (subclavian, jugular) should not be used. In case of serious bleeding that cannot be stopped by applying a pressure bandage, the administration of the drug and heparin should be stopped immediately.

The risk of bleeding is greatest at the femoral artery catheter insertion site during PTCA. Caution should be exercised and it should be ensured that only the anterior wall of the femoral artery is punctured. The femoral artery access system can be removed after coagulation function returns to normal: aPTT is less than 45 seconds, which usually occurs 3-4 hours after stopping heparin administration. After removing the access system, hemostasis should be achieved followed by careful monitoring for at least 2-4 hours before discharge from the hospital.

If the platelet count drops below 100,000/µl, the administration of eptifibatide and heparin should be stopped and necessary therapeutic measures should be taken. If there is a history of thrombocytopenia with the use of other parenteral inhibitors of platelet glycoprotein IIb/IIIa receptors, particularly careful monitoring is required. A reversible 5-fold increase in bleeding time may be observed. Bleeding time returns to baseline within 2-6 hours after discontinuation of eptifibatide.

Concomitant use with low molecular weight heparin is not recommended due to lack of clinical experience. The use of heparin is recommended in all cases (in the absence of contraindications to its use).

Before starting therapy, it is recommended to determine prothrombin time, aPTT, serum creatinine, platelet count, hemoglobin, and hematocrit to identify possible hemostasis disorders. The last 3 parameters should be continuously monitored for 6 hours after the start of therapy, then once daily throughout the therapy (or more often – in case of a decrease in parameters). If thrombocytopenia is below 100,000/µl, repeated tests should be performed to exclude pseudothrombocytopenia; heparin administration should be discontinued.

Drug Interactions

When used concomitantly with streptokinase, the risk of bleeding increases.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.