Integrillin® [Eptifibatide]

Pharmacological properties

Eptifibatide is an inhibitor of platelet aggregation, belongs to the class of rgd (arginine-glycine-aspartate) mimetics. it reversibly and dose-dependently inhibits platelet aggregation, preventing the interaction of fibrinogen, von willenbrand factor and other ligands with glycoprotein iib / iiia receptors.

With iv administration, eptifibatide inhibits platelet aggregation ex vivo, the degree of which depends on the dose and concentration of the drug. Inhibition of platelet aggregation is reversible; 4 hours after the end of the infusion, platelet function is restored by more than 50% compared with the initial level.

Eptifibatide does not directly affect prothrombin or activated partial thromboplastin time (APTT). The pharmacodynamic properties of eptifibatide have no differences in gender and age.

The pharmacokinetics of eptifibatide are linear and dose-dependent when administered as a bolus at a dose of 90–250 mcg / kg, with an infusion rate of 0.5–3 mcg / kg / min. When the drug was administered by infusion at a dose of 2.0 μg / kg / min in patients with coronary atherosclerosis, the stable level of the drug in plasma was 1.5–2.2 μg / ml. The level of the drug in blood plasma quickly reaches a stable concentration with the previous administration of a bolus at a dose of 180 mcg / kg. With the introduction of the drug according to the recommended scheme (bolus, and then infusion), the concentration quickly reaches a maximum, then decreases slightly and reaches a stable level for 4-6 hours. With coronary angioplasty, this decrease in concentration can be prevented by administering a second bolus at a dose of 180 mcg / kg 10 minutes after the first. The degree of binding of eptifibatide to human plasma proteins is about 25%. The plasma half-life is about 2.5 hours, clearance is 55–58 ml / kg / h, and the distribution volume is 1850–260 ml / kg. In healthy people, part of the renal clearance of the drug from the total clearance is about 50%; most of the drug is excreted in the urine unchanged and in the form of metabolites. No major metabolites have been found in human plasma.

Indications

Acute coronary syndrome (unstable angina, myocardial infarction without q wave).

During percutaneous transluminal coronary angioplasty (PTCA), including intracoronary stenting in order to prevent thrombolytic occlusion of the affected artery and acute ischemic complications.

Application

Integrilin rr for intravenous jet (2 mg / ml) and integril rr for intravenous drip (0.75 mg / ml) are used in accordance with the schemes described below.

Acute coronary syndrome

Immediately after the diagnosis is established, 180 μg / kg body weight is injected intravenously, then 2 μg / kg / min (at a creatinine clearance level of ≥50 ml / min) or 1 μg / kg / min (at the level of creatinine clearance ≥30, but 50 ml / min), which lasts up to 72 hours until the start of coronary artery bypass grafting or until the patient is discharged from the hospital (if it occurs earlier). In the event that the patient is given PTCA according to urgent indications, the Integrilin infusion is continued for another 18-24 hours after the intervention (the maximum total duration of therapy is 96 hours). Patients with a body weight of more than 121 kg are given no more than 22.6 mg of the drug by bolus and no more than 15 mg / h (at a creatinine clearance level of ≥50 ml / min) or 7.5 mg / h (at a creatinine clearance level of ≥30, but 50 ml / min) as an infusion.

READ

Immediately before the start of the manipulation, 180 mcg / kg of body weight is bolus administered intravenously, then they switch to a continuous infusion of the drug at 2 mcg / kg / min (at a creatinine clearance level of ≥50 ml / min) or 1 mcg / kg / min (at the level of creatinine clearance ≥30, but 50 ml / min). 10 minutes after the first bolus, the bolus is re-administered at a dose of 180 mcg / kg. The infusion is continued for 18-24 hours or until the patient is discharged from the hospital (if it occurs earlier). The minimum duration of drug administration is 12 hours.Patients weighing more than 121 kg are given no more than 22.6 mg of the drug in the form of a bolus and no more than 15 mg / h (at a creatinine clearance level of ≥50 ml / min) or 7.5 mg / h (at a creatinine clearance level of ≥30 , but 50 ml / min) as an infusion.

The dose of Integrilin can be determined depending on the UNIT of the patients body weight according to the table below:

Liver failure

The experience of using the drug in patients with liver failure is very limited. Use with caution in patients with hepatic insufficiency, which may have coagulation disorders.

Renal failure

In patients with moderate renal failure (creatinine clearance ≥30, but 50 ml / min), Integrilin can be used bolus at a dose of 180 μg / kg body weight, then iv in a dose of 1.0 μg / kg / min during treatment. The experience of using the drug for the treatment of patients with more severe renal failure is limited.

Use in children

Data on the safety and efficacy of Integridine in children and adolescents are limited, therefore, the use of the drug in patients under the age of 18 is not recommended.

Contraindications

Hypersensitivity to any component of the drug; severe pathological bleeding during the previous 30 days (excluding menstrual bleeding); a stroke (of any origin) during the previous 30 days or a history of hemorrhagic stroke; history of intracranial diseases (neoplasm, arteriovenous malformations, aneurysms); extensive surgery or severe trauma in the previous period (at least 6 weeks); a history of hemorrhagic diathesis; thrombocytopenia (100,000 cells / mm3); prothrombin time is 1.2 times longer than the control or inr ≥2.0; severe ag (systolic pressure 200 mm Hg. Art. or diastolic pressure 110 m Hg. Art.) on the background of antihypertensive therapy; clinically pronounced impaired liver function; severe renal failure (creatinine clearance 30 ml / min) or dependence on renal dialysis; simultaneous or planned parenteral use of another parental iib / iiia glycoprotein receptor blocker.

Side effects

Clinical researches

Bleeding

Adverse reactions that occur in patients treated with Integrilin in most cases were associated with bleeding or cardiovascular disorders. The most common adverse reactions were bleeding, which, according to the TIMI classification (Thrombolysis in Myocardial Infarction research group for thrombolysis in myocardial infarction) used in the studies, was divided into massive (intracranial or clinically significant local bleeding associated with a decrease in hemoglobin level of ≥5 g / dl) or small (macrohematuria or hemathemesis, or the observed loss of blood associated with a decrease in hemoglobin level of ≥3 g / dl).

According to a study on the treatment of unstable angina pectoris and myocardial infarction without an abnormal Q wave (PURSUIT), the most common complication (1/10) of the treatment was minor bleeding (13.1% with Integrilin compared with 7.6% with placebo). Most often, bleeding was noted during invasive procedures (coronary artery bypass surgery or at the access site through the femoral artery). The incidence of side effects during coronary artery bypass grafting was 2.8% when using Integrilin compared with 2.7% when using placebo.Small bleeding (frequency 1%) was reported, such as genital bleeding, from the site of the femoral artery puncture, oropharyngeal and gastrointestinal bleeding, and a decrease in hemoglobin / hematocrit. Bleeding more often occurred in patients who also received heparin during coronary artery surgery and whose activated coagulation time (ABC) exceeded 350 s.

Massive bleeding occurred more often (1/10) in patients treated with Integrilin compared with placebo (10.8 and 9.3%, respectively). Massive bleeding (1%) included bleeding from the site of the puncture of the femoral artery, oropharyngeal and gastrointestinal bleeding, and a decrease in hemoglobin / hematocrit. Less commonly reported bleeding from the genitals, retroperitoneal and intracranial bleeding.

The incidence of severe or life-threatening bleeding with Integrilin is higher (1/100, but 1/10) than with placebo: 1.9 versus 1