Aprokardiks (Solution) Instructions for Use

Marketing Authorization Holder

Argumentum, LLC (Russia)

Manufactured By

S.C. Rompharm Company S.R.L. (Romania)

ATC Code

B01AC16 (Eptifibatide)

Active Substance

Eptifibatide (Rec.INN registered by WHO)

Dosage Forms

	Aprokardiks	Solution for intravenous administration 0.75 mg/ml
		Solution for intravenous administration 2 mg/ml

Dosage Form, Packaging, and Composition

Solution for intravenous administration

100 ml – bottles – cardboard packs – By prescription

Solution for intravenous administration

10 ml – bottles – cardboard packs – By prescription

Clinical-Pharmacological Group

Antiplatelet agent

Pharmacotherapeutic Group

Antithrombotic agents; antiplatelet agents, other than heparin

Pharmacological Action

Eptifibatide is an antiplatelet agent, a synthetic cyclic heptapeptide containing 6 amino acids and a mercaptopropionyl residue – deaminocysteyinyl. It is 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 recovers by more than 50%. It does not have a noticeable effect on prothrombin time and aPTT.

Pharmacokinetics

The pharmacokinetics of eptifibatide are linear and dose-dependent when administered as a bolus in doses ranging 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 rapidly 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. Plasma protein binding is 25%.

The half-life (T_1/2) is 2.5 hours, clearance is 55-58 ml/kg/h and the volume of distribution (V_d) is 185-260 ml/kg.

In healthy individuals, the renal clearance fraction of the total is 50%; most is excreted by the kidneys unchanged and as metabolites. The main metabolites have not been 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 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.

Continue this infusion until hospital discharge or for up to 72 hours.

For patients undergoing Percutaneous Coronary Intervention (PCI), administer the same bolus and infusion regimen.

If the PCI procedure occurs during the infusion for ACS, continue the infusion for 20-24 hours post-procedure, for a maximum total duration of 96 hours.

For patients undergoing elective PCI, administer an intravenous bolus of 180 mcg/kg immediately before the procedure.

Immediately follow the initial bolus with a continuous infusion of 2 mcg/kg/min.

Administer a second 180 mcg/kg bolus 10 minutes after the first.

Continue the infusion for the duration of the hospitalization, for a minimum of 12 hours and up to 24 hours post-procedure.

In all cases, reduce the infusion rate by 50% to 1 mcg/kg/min in patients with an estimated creatinine clearance of less than 50 mL/min.

Do not administer to patients on hemodialysis.

Base the bolus dose and infusion rate on the patient’s actual body weight.

Discontinue eptifibatide infusion prior to coronary artery bypass graft (CABG) surgery.

Adverse Reactions

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

From the hematopoietic system thrombocytopenia (platelet count <100,000 cells/mcL, 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, for clinical reasons, 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 with caution during pregnancy 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, for clinical reasons, 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 sites of possible bleeding (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, administration of the drug should be stopped immediately. Before elective surgery, administration of the drug is stopped 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, 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 to ensure 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 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 falls below 100,000/mcL, administration of eptifibatide and heparin should be stopped and necessary therapeutic measures 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 if the parameters decrease). If thrombocytopenia below 100,000/mcL occurs, repeated tests should be performed to rule out pseudothrombocytopenia; heparin administration should be discontinued.

Drug Interactions

Concomitant use with streptokinase increases the risk of bleeding.

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.