Integrilin (Integrilin)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceEptifibatidEptifibatid
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  • Integrilin
    solution in / in 
    GlaxoSmithKline Trading, ZAO     Russia
    • Dosage form: & nbspsolution for intravenous administration
    Composition:

    Component name

    Amount in 1 ml


    0.75 mg / ml

    2.0 mg / ml

    Active substance

    Eptifibatid

    0.75 mg

    2.0 mg

    Excipients

    Citric acid
    monohydrate

    		 5,25
    mg

    5.25 mg




    Sodium hydroxide to adjust the value pH to 5.35

    q.s.

    q.s.

    Water for injections

    up to 1.0 ml

    up to 1.0 ml
    Description:

    A clear, colorless solution.

    Pharmacotherapeutic group:Antiaggregant agent
    ATX: & nbsp

    B.01.A.C   Inhibitors of platelet aggregation (excluding heparin)

    B.01.A.C.16   Eptifibatid

    Pharmacodynamics:

    Mechanism of action

    Eptifibatid is a synthetic cyclic heptapeptide containing 6 amino acid residues, including one cysteinamide and one mercaptopropionyl residue, deamino-cysteinyl. Eptifibatid is an inhibitor of platelet aggregation and belongs to the class of arginine-glycine-aspartate mimetics. Eptifibatid reversibly inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor and other adhesive ligands to glycoprotein IIb / IIIa receptor platelets.

    Eptifibatide causes a dose-dependent and concentration-inhibiting platelet aggregation, as demonstrated ex vivo with the use of adenosine diphosphate (ADP) and other agonists inducing platelet aggregation. The effect of eptifibatide is observed immediately after intravenous bolus injection at a dose of 180 μg / kg. The regimen followed by continuous intravenous infusion at a dose of 2.0 μg / kg / min provides more than 80% inhibition of platelet aggregation ex vivo, induced by ADP, at physiological concentrations of calcium, in more than 80% of patients. Inhibition of platelet aggregation is reversible; 4 hours after the cessation of continuous infusion at a dose of 2.0 μg / kg / min, the platelet function is restored to the baseline by more than 50%. When conducting measurements of ADP-induced platelet aggregation ex vivo at physiological concentrations of calcium (anticoagulant D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (RRASC)) in patients with unstable angina and myocardial infarction without a tooth Q a concentration-dependent inhibition with IR50 (concentration inhibiting aggregation by 50%) of 557 ng / ml. and IR80 (concentration inhibiting aggregation by 80%), which is 1107 ng / ml.The time of bleeding with the use of the drug Integrilin intravenously in the form of a bolus and infusion reversibly increases up to 5 times, this index returns to the baseline within 2-6 hours after the infusion is terminated. When used as a monotherapy eptifibatide has no significant effect on prothrombin time (PT) and activated partial thromboplastin time (APTT).

    Pharmacokinetics:

    The pharmacokinetics of eptifibatide is linear and dose-dependent in the bolus administration at a dose of 90 to 250 μg / kg and infusion at a rate of 0.5 to 3.0 μg / kg / min. When infusion of the drug at a dose of 2.0 μg / kg / min in patients with coronary heart disease, the average equilibrium concentration of eptifibatide in plasma is set in the range of 1.5-2.2 μg / ml. This concentration in the plasma is achieved more quickly if the infusion is preceded by a bolus injection at a dose of 180 μg / kg. The degree of binding of eptifibatide to human plasma proteins is about 25%. In the same population of patients, the plasma half-life is approximately 2.5 hours, the plasma clearance is 55-80 ml / kg / h, and the distribution volume is approximately 185-260 ml / kg. In healthy patients, the proportion of renal excretion from total clearance is about 50%; approximately 50% of the withdrawn amount of the substance is output in unmodified form.

    A moderate increase in the half-life and volume of distribution is observed in older patients, patients with reduced body weight (<74 kg) and / or reduced creatinine clearance (CC). The dose and sex of the patient do not affect the pharmacokinetics of the preparation Integrilin. For renal insufficiency of mild severity (KK> 50 ml / min according to the Cockcroft-Gault formula), dose adjustment with bolus or infusion administration is not required. For renal insufficiency of moderate severity (KK ≥30- <50 ml / min according to Cockcroft-Gault formula) dose correction is recommended. In patients with moderate or severe renal insufficiency (CK <50 ml / min), a decrease in the clearance of eptifibatide by approximately 50% is observed and an increase in equilibrium plasma concentrations is approximately two-fold (see "Special instructions", "Dosage and administration" ).

    Indications:

    · Early prevention of myocardial infarction in patients with unstable angina or myocardial infarction without a tooth Q, marking the last pain attack within 24 hours, with ECG changes and / or increased activity of cardiospecific enzymes;

    · prevention of sudden closure of the vessel and associated acute ischemic complications in percutaneous transluminal coronary angioplasty (PTCA).

    The preparation Integrilin is intended for use together with acetylsalicylic acid and unfractionated heparin.

    Contraindications:

    - Hypersensitivity to the active ingredient or any other component of the drug;

    - gastric or intestinal bleeding, severe genital and urologic bleeding, or other severe pathological bleeding (with the exception of menstrual bleeding) within the last 30 days;

    - acute cerebrovascular accident within the last 30 days or a history of hemorrhagic stroke;

    - presence in the anamnesis of intracranial disease (neoplasm, arteriovenous malformation, aneurysm);

    - "big" surgery for the last 6 weeks;

    - a hemorrhagic diathesis in the anamnesis;

    - thrombocytopenia (<100 000 cells / mm3);

    - prothrombin time greater than 1.2 from the control or international normalized ratio (INR) ≥ 2.0;

    - severe arterial hypertension (systolic blood pressure above 200 mm Hg.or diastolic blood pressure above 110 mm Hg. ) against the background of antihypertensive therapy;

    - clinically significant hepatic impairment;

    - simultaneous or planned use of another inhibitor of glycoprotein IIb / IIIa receptors;

    - severe renal failure (creatinine clearance <30 mL / min);

    - the need for hemodialysis.

    Carefully:

    Caution should be exercised when using the drug Integrilin with other drugs that affect the hemostatic system: thrombolytics, oral anticoagulants, dextran solutions, adenosine, nonsteroidal anti-inflammatory drugs, including sulfinpyrazone, preparations containing prostacyclin, dipyridamole, ticlopidine and clopidogrel.

    The risk of bleeding with the simultaneous appointment of the drug Integrilin and streptokinase, used to treat acute myocardial infarction, is increasing. Joint use of the drug Integrilin and heparin is recommended in all cases, in the absence of contraindications to the use of heparin, for example, thrombocytopenia associated with the administration of heparin, in the anamnesis.

    In connection with the lack of clinical experience, the use of the preparation Integralin simultaneously with low molecular weight heparin is necessary with caution.

    Children under the age of 18

    The safety and effectiveness of the use of the drug Integrilin in patients under the age of 18 years is not established, therefore, the use in this category of patients is not recommended.
    Pregnancy and lactation:

    Pregnancy

    Clinical studies on the use of the drug Integrilin in pregnant women have not been conducted. However, studies on the effect on reproductive function were performed on rats and rabbits using doses, respectively, 8 and 4 times higher than the dose intended for humans. In these studies, there was no evidence of impaired fertile function or adverse effects on the fetus associated with the use of eptifibatide. Since animal studies are not considered sufficient to predict possible reactions in humans, Integralin should be used during pregnancy only if the benefit to the mother exceeds the potential risk to the fetus.

    Breast-feeding

    There are no data on the penetration of eptifibatide into breast milk.It is recommended to stop breastfeeding with Integrilin.

    Dosing and Administration:

    The drug Integrilin is intended for use in adults aged 18 years and older.

    A solution for intravenous administration at a concentration of 0.75 mg / ml (for infusion) and an intravenous solution at a concentration of 2 mg / ml (for bolus administration) should be used together according to the instructions.

    It is recommended simultaneous use of the drug Intergilin and heparin, except for situations when the use of heparin is contraindicated, for example, in the case of thrombocytopenia associated with the use of heparin, in the anamnesis.

    The preparation Integrilin is also intended for simultaneous use with acetylsalicylic acid, since acetylsalicylic acid is a standard component of the treatment of patients with acute coronary syndrome, except when the use of acetylsalicylic acid is contraindicated.

    Patients undergoing percutaneous coronary intervention (PCI)

    The recommended dose of eptifibatide for adult patients with CC ≥ 50 mL / min (according to formula

    Cockroft-Gault) intravenously bolus at a dose of 180 μg / kg immediately before the beginning of the manipulation, after 10 minutes after the first bolus another 180 μg / kg is injected in the form bolus. Simultaneously with the first bolus, a continuous infusion of the drug is started at a dose of 2.0 μg / kg / min. Infusion is continued until the patient is discharged from the hospital or within 18-24 hours after PCI. The minimum recommended infusion duration is 12 hours.

    Patients with creatinine clearance ≥30 - <50 ml / min, which is performed by percutaneous coronary intervention (PCI)

    The recommended dose of Eptifibatide for adult patients with CK ≥ 30- <50 ml / min (Cockcroft-Gault formula): intravenous bolus at a dose of 180 mcg / kg immediately before the beginning of the manipulation, another 180 mcg / kg in 10 min after the first bolus type of bolus. Simultaneously with the first bolus, a continuous infusion of the drug is started at a dose of 1.0 μg / kg / min. Infusion is continued until the patient is discharged from the hospital or within 18-24 hours after PCI. The minimum recommended infusion duration is 12 hours.

    Patients with acute coronary syndrome (patients with unstable angina or myocardial infarction without a tooth Q)

    The recommended dose of Eptifibatide for adult patients with CC ≥ 50 mL / min (Cockcroft-Gault formula): intravenously bolus at a dose of 180 μg / kg as soon as possible after diagnosis, then begin continuous infusion at a dose of 2.0 μg / kg / min , which is continued up to 72 hours before the start of coronary artery bypass surgery or until discharge from the hospital, depending on what happens before.

    If PTCA is administered during treatment, the infusion is continued for 20-24 hours after PTCA, the maximum total duration of administration is 96 hours.

    Patients with acute coronary syndrome (patients with unstable angina or myocardial infarction without Q wave) and creatinine clearance ≥ 30-< 50 ml / min

    The recommended dose of Eptifibatide for adult patients with CK ≥ 30- <50 mL / min (Cockcroft-Gault formula): intravenously bolus at a dose of 180 μg / kg as soon as possible after diagnosis, then immediately begin continuous infusion at a dose of 1.0 μg / kg / min, which is continued up to 72 hours before the start of coronary artery bypass surgery or until discharge from hospital, whichever occurs earlier.

    If PTCA is administered during treatment, the infusion is continued for 20-24 hours after PTCA, the maximum total duration of administration is 96 hours.

    To calculate the creatinine clearance in ml / min, use the Cockcroft-Gault formula with the actual body weight:

    Men: (140 - age in years) x (actual body weight in kg) / 72 x (serum creatinine in mg / dL)

    Women: (140 - age in years) x (actual body weight in kg) x (0.85) / 72 x (serum creatinine in mg / dL)

    Patients weighing over 121 kg receive no more than 22.6 mg of the bolus preparation and not more than 15 mg / hr (with a creatinine concentration below 2.0 mg / dl) or 7.5 mg / hr (with a creatinine concentration of 2 , 0 to 4.0 mg / dL) as an infusion.

    Emergency or "planned" surgical intervention

    If during the therapy with Integralin the patient needs an urgent or urgent heart surgery, the infusion should be stopped immediately. If the patient needs a "planned" intervention, the infusion should be discontinued to allow time to restore platelet function to normal levels.

    Patients who require thrombolytic therapy (for example,. transmural myocardial infarction with a new pathological prong Q on the ECG)

    Experience with this group of patients is not available, the use of the drug is not recommended.

    Instructions for the introduction of the drug Integrilin

    1. Before administration, the solution should be checked for the presence of turbidity or foreign particles or discoloration; the solution can be administered only in the absence of them. During the introduction of solution protection from light is not required.

    2. The drug Integrilin can be administered in the same system as alteplase, atropine sulfate, dobutamine, heparin, lidocaine, pethidine, metoprolol, midazolam, morphine, nitroglycerin, verapamil.

    The preparation Integrilin can not be administered in the same system as furosemide.

    3. The preparation Integrilin can be administered in the same system with 0.9% sodium chloride solution or its mixture with 5% dextrose. When using any of these solvents, the administration solution can also contain up to 60 mmol / L potassium chloride. Incompatibility with materials used for the manufacture of systems for intravenous administration was not noted.

    It is not recommended to mix the drug Integrilin with drugs, compatibility with which is not established.

    4. For bolus administration, the Integralin preparation should be drawn into a syringe from a vial containing 10 ml of the drug and injected intravenously in strips for 1-2 minutes.

    5. Immediately after the bolus, intravenous drip infusion of the drug should be started. In the presence of a pump that allows to regulate the infusion rate, the preparation Integrilin can be injected directly from a vial containing 100 ml of the drug without diluting. The system for the administration of the drug Integrilin from a vial containing 100 ml of the drug should have an air outlet; The needle for connecting the system to the vial should be injected strictly through the center of the vial plug.

    The remainder of the drug in the vial is not subject to further use and must be disposed of.

    Side effects:

    Most of the undesirable phenomena with the use of the drug Integrilin are associated with the development of bleeding or the occurrence of disorders of the heart or cardiovascular system, which is often observed in this population of patients.

    Clinical data

    The incidence of adverse events presented below was determined based on two Phase III clinical trials (PURSUIT and ESPRIT).

    PURSUIT - a double-blind, randomized study of the efficacy and safety of the use of Integralin versus placebo to reduce mortality and numbercases of repeated myocardial infarction in patients with unstable angina or myocardial infarction without a tooth Q.

    ESPRIT - Double-blind, multicenter, randomized. a placebo-controlled study in parallel groups to study the safety and efficacy of using eptifibatide in patients with scheduled non-urgent percutaneous coronary intervention (PCI) with intracoronary stenting.

    Data on adverse events, including bleeding, in the study PURSUIT received from the moment of discharge from the hospital before the visit on the 30th day. Phenomena of bleeding in the study ESPRIT were recorded within 48 hours, and phenomena not related to bleeding were recorded for 30 days. To classify the incidence of massive and mild bleeding in studies PURSUIT and ESPRIT bleeding criteria TIMI (classification according to the criteria of the group for the study of thrombolysis in myocardial infarction). Research data PURSUIT were collected within 30 days, while the data obtained in the study ESPRIT, were limited to events that occurred within 48 hours or before discharge, depending on what happened earlier.

    When used in the recommended therapeutic doses that were used in the study PURSUIT (involving about 11,000 patients), bleeding was the most common complication of therapy with eptifibatide. Invasive procedures on the heart (aortocoronary bypass or access to the femoral artery) were most often accompanied by bleeding.

    In the study PURSUIT, slight bleeding was defined as spontaneous hematemesis, spontaneous hematemesis, bleeding with a decrease in hemoglobin concentration of more than 3 g / dL, or a decrease in hemoglobin concentration of more than 4 g / dl in the absence of a visible source of bleeding. Light bleeding was a very frequent complication of the use of the drug Integrilin (> 1/10, or 13.1% with the use of the preparation Integrilin versus 7.6% with placebo). Bleeding was more common in patients receiving heparin concomitantly with PCI when the activated clotting time (ABC) exceeded 350 seconds (see section "Special instructions", subsection "Application of heparin").

    In the study PURSUIT massive bleeding was defined as intracranial bleeding or a decrease in hemoglobin concentration by more than 5 g / dL.Massive bleeding with the use of the drug Integrilin in this study was observed very often (≥1 / 10 or 10.8% when using the preparation Integrilin versus 9.3% with placebo), excluding the vast majority of patients who did not undergo aortocoronary bypass within 30 days after inclusion in the study, in which this phenomenon was not observed infrequently. In patients undergoing coronary artery bypass grafting, the frequency of bleeding with INTEGRYLIN was not increased in comparison with patients receiving placebo. In a subgroup of patients undergoing PCI. extensive bleeding was observed frequently: in 9.7 % patients with the use of the preparation Integrilin compared with 4.6% in patients receiving placebo.

    The incidence of severe or life-threatening bleeding with Integrilin was 1.9% compared to 1.1% for placebo. When using the drug Integrilin, the need for blood transfusions was moderately increased (11.8% - Integrilin, 9.3% - placebo).

    The adverse events presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence.The frequency of occurrence is determined as follows: very often (≥1 / 10), often (≥1 / 100 and <1/10). infrequently (≥ 1/1 000 and <1/100), rarely (≥1 / 10,000 and <1/1 000), very rarely (<1/10 000, including individual cases). The absolute frequency of messages without frequency in the placebo application is indicated. In the presence of data on individual adverse events from two studies (PURSUIT and ESPRIT), To determine the frequency of adverse events, the highest indicated frequency was used.

    It should be noted that communication with the use of the drug was not established for all undesirable phenomena.

    The frequency of serious adverse events that are not related to bleeding (arterial hypotension, etc.), when using the drug Integrilin, does not differ from that in placebo.

    Violations of the blood and lymphatic system

    Very often: bleeding (massive and mild bleeding, including bleeding in aortocoronary bypass and access through the femoral artery, gastrointestinal bleeding, urogenital bleeding, retroperitoneal and intracranial hemorrhage, hematemesis, hematuria, intraoral / oropharyngeal bleeding, haematocrit / hemoglobin bleeding and others).

    Infrequent: thrombocytopenia.

    Disturbances from the nervous system

    Infrequently: cerebral ischemia.

    Heart Disease

    Often: cardiac arrest, ventricular fibrillation, ventricular tachycardia, congestive heart failure, atrioventricular block, atrial fibrillation.

    Vascular disorders

    Often: cardiogenic shock, arterial hypotension, phlebitis.

    Heart failure, congestive heart failure, atrial fibrillation, arterial hypotension and cardiogenic shock, which were often recorded in the study PURSUIT, were the phenomena associated with the underlying disease.

    Post-registration data

    Violations of the blood and lymphatic system

    Very rarely: bleeding with a fatal outcome (mainly affecting the central and peripheral nervous system: hemorrhagic stroke or intracranial hemorrhages); pulmonary hemorrhage, acute deep thrombocytopenia. hematoma.

    Immune system disorders

    Very rarely: anaphylactic reactions.

    Disturbances from the skin and subcutaneous tissues

    Very rarely: rash, undesirable events at the injection site (eg, urticaria).

    Overdose:

    Information on an overdose of the drug Integrilin in humans is very limited. Signs of serious adverse events associated with the accidental use of large doses with bolus administration, rapid infusion introduction that was reported as an overdose, or excess of cumulative doses, was not observed. There were reported 9 patients who, within the framework of a clinical trial PURSUIT received a bolus dose and / or an infusion dose more than 2 times that indicated in the protocol, or that were identified by the investigator as having been given an overdose. In this case, no massive bleeding was observed in any of the patients; one patient underwent coronary artery bypass grafting, and only moderate bleeding was observed. None of the patients had intracranial bleeding.

    When an overdose of the drug Integrilin is not ruled out the possibility of developing bleeding. Due to the short half-life and rapid clearance, Active Ingrolin can be quickly reduced by stopping the infusion. The drug Integrilin can also be excreted by hemodialysis.In some cases, transfusion may be necessary to treat an overdose.

    Interaction:

    The preparation Integrilin does not cause an increase in the risk of large and small bleeding when used simultaneously with warfarin and dipyridamole. Patients with a prothrombin time> 14.5 seconds who received Integralin at the same time as warfarin did not have an increased risk of bleeding.

    There are limited data on the use of the preparation Integrilin in patients receiving thrombolytic drugs. There is no unambiguous evidence that Integrulin increases the risk of developing large and small bleedings associated with the tissue plasminogen activator as in patients undergoing PTCA. and in patients with acute myocardial infarction. However, in clinical studies, the preparation Integriglin increased the risk of bleeding when administered with streptokinase in patients with acute myocardial infarction. In a study in 181 patients with acute myocardial infarction, the preparation Integralin (the bolus injection dose reached 180 μg / kg, followed by infusion up to 2 μg / kg / min up to 72 hours) was administered simultaneously with streptokinase (1.5 million units more than 60 minutes) .In the case of a maximum infusion rate (1.3 μg / kg / min and 2.0 μg / kg / min), the use of Integrilin was associated with an increase in the frequency of bleeding and the need for transfusions as compared with monotherapy with streptokinase.

    In a clinical study in patients with acute myocardial infarction with segment elevation ST the combined use of a combination of reduced doses of tenecteplase and the preparation Integriglin led to a significant increase in the risk of developing massive and mild bleeding (compared with placebo and the use of Integralin without tenectoplazy).

    The preparation Integrilin is not compatible with furosemide.

    In clinical trials, 95% of patients who underwent non-urgent PCI with intracoronary stenting were assigned clopidogrel simultaneously with acetylsalicylic acid before or within 48 hours after PCI and daily after PCI.

    Special studies to study the pharmacokinetic interaction of the drug Integrilin with other drugs have not been conducted. However, in carrying out clinical studies, there was no evidence of a pharmacokinetic interaction between the Integrilin preparation and such commonly used in patientswith cardiovascular diseases amlodipine, atenolol, atropine, captopril, cefazolin, diazepam, digoxin, diltiazem, diphenhydramine, enalapril, fentanyl, furosemide, heparin, lidocaine, lisinopril, metoprolol, midazolam, morphine, nitrates, nifedipine, warfarin.

    Special instructions:

    The drug Integrilin is intended for use only in a hospital.

    Bleeding

    The drug Integrilin is an antithrombotic agent that suppresses platelet aggregation; Therefore, in the course of treatment with Integralin, all patients should be carefully examined to detect possible bleeding, especially women, elderly patients, as well as patients with low body weight, who are at greatest risk of bleeding (see "Side-Effects" section). If serious bleeding occurs, which can not be stopped by applying a pressure bandage, you should immediately stop the infusion of the drug and any concomitant heparin.

    Risk of bleeding in patients undergoing PTCA. is greatest in the place of arterial access.It is necessary to carefully monitor the places of possible bleeding, for example, the place of insertion of the catheter, the place of arteriopuncture, venipuncture or needle puncture, the place of venesection, should be taken into account the possibility of bleeding from the gastrointestinal tract and urogenital tracts, retroperitoneal bleeding. There may also be bleeding in the central and peripheral nervous system.

    Control of access to the femoral artery

    When using the drug Integrilin, the risk of bleeding is greatest at the site of insertion of the catheter into the femoral artery during PTCA. Care should be taken to ensure that only the front wall of the femoral artery is punctured. The introducer from the femoral artery can be removed after restoration of the coagulation function to the norm: the activated clotting time is less than 180 s (usually 2-6 hours after heparin cancellation). After removal of the introducer, hemostasis should be performed followed by careful monitoring until discharge from the hospital.

    Thrombocytopenia and immunogenicity, associated with the use of inhibitors IIb / IIIa receptors

    The preparation Integrilin suppresses the aggregation of platelets, but does not affect their viability.The frequency of thrombocytopenia was low and similar to that in patients treated with placebo was observed in clinical trials, and in the rare case reports of immune thrombocytopenia during postmarketing observations. The presence in the plasma-borne factors, which can bind to eptifibatide and glycoprotein IIb / IIIa receptors means that may develop an immune response when first thrombotic held applying inhibitors of glycoprotein IIb / IIIa receptor in patients or re-receiving eptifibatide.

    The mechanism (immune and / or non-immune) of the effect of eptifibatide on the development of thrombocytopenia has not been fully studied. Due to the fact that the repeated impacts of any inhibitor of glycoprotein IIb / IIIa receptor antagonists (abciximab or eptifibatide et al.) Or primary effect of inhibitors of glycoprotein IIb / IIIa receptor may be accompanied thrombocytopenic immune-mediated response, it should be careful to control the possible cases of thrombocytopenia accompanied by arterial hypotension and / or other symptoms of hypersensitivity.

    When confirming a decrease in the number of platelets to <100,000 / mm3 or acute deep thrombocytopenia, discontinuation of treatment with any medication that may have a thrombocytopenic effect, including eptifibatide, heparin and clopidogrel, should be immediately considered. It is necessary to begin maintenance therapy, as well as monitor the number of platelets to correct treatment and establish etiology. If thrombocytopenia is not associated with the use of eptifibatide, the therapy can be resumed after the normalization of the platelet count.

    Increased bleeding time

    The time of bleeding with the use of the drug Integrilin intravenously in the form of a bolus and infusion increases up to 5 times. This increase is rapidly reversible after discontinuation of the infusion, this index returns to the baseline within 2-6 hours. When used as monotherapy, the preparation Integrilin has no significant effect on prothrombin time (PT) and activated partial thromboplastin time (APTT).

    The use of heparin

    Joint use of the drug Integrilin and heparin is recommended in all cases,in the absence of contraindications to the use of heparin, for example, thrombocytopenia associated with the administration of heparin, in the anamnesis.

    Patients with unstable angina or myocardial infarction without a Q wave

    For patients with a body weight of 70 kg or more, the recommended bolus dose is 5000 units, followed by a constant infusion of 1000 U / h. For patients weighing less than 70 kg, the bolus dose is 60 U / kg, followed by infusion of 12 U / kg / h.

    The APTTV indicator should be monitored to maintain values ​​in the range of 50-70 s.

    Coronary angioplasty

    When conducting PTCA in patients, it is necessary to monitor ABC (activated clotting time), its values ​​should be within 300-350 s. If the value of activated blood coagulation time exceeds 300 s, the use of heparin should be stopped and not resumed until the reduction is less than 300 s.

    Non-acute PTCA with intracorporal stenting

    For patients who did not enter heparin within 6 hours before the intervention, an initial bolus injection of heparin at a dose of 60 U / kg is recommended. The target ABC value during the procedure is 200-300 s.During the PTCA procedure, heparin can additionally be administered bolus to maintain the ABC value in this range.

    Patients with hepatic insufficiency

    The experience with the use of eptifibatide in patients with hepatic insufficiency is extremely limited (see the section "Contraindications"). In patients with hepatic insufficiency, the drug should be used with caution, since in such patients, the drug may affect blood coagulability.

    Patients with renal insufficiency

    For renal insufficiency of mild severity (KK> 50 ml / min according to the Cockcroft-Gault formula), the preparation Integrilin can safely be used in a standard dosage. For moderate or severe renal failure (CK <50 ml / min according to the Cockcroft-Gault formula), the clearance of eptifibatide is reduced by approximately 50%, and the equilibrium plasma concentrations are approximately doubled. In patients with moderate or severe renal failure who undergo regular infusions at a dose of 2 μg / kg / min. increased risk of bleeding. Therefore, in such patients, the dose during the infusion should be reduced to 1 μg / kg / min (see section "Method of administration and dose").Clinical studies involving patients on dialysis have not been conducted.

    Use in children

    The safety and effectiveness of the use of the drug Integrilin in children is not established.

    Monitoring of laboratory indicators

    The change in laboratory parameters during the treatment with the drug Integrilin is a consequence of the known pharmacological properties of the preparation, for example, inhibition of platelet aggregation. Thus, changes in laboratory indicators characterizing bleeding (eg, bleeding time) are observed frequently and are expected. With the use of the preparation Integrilin and with the use of placebo, there were no obvious differences in such parameters as hemoglobin, hematocrit, platelet count, liver function parameters (concentration of aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase) and kidney function (serum creatinine concentration, blood urea nitrogen) .

    Effect on the ability to drive transp. cf. and fur:

    Studies on the effect of eptifibatide on the ability to drive vehicles or work with mechanisms have not been carried out.The pharmacological properties of eptifibatide indicate that there is no adverse effect on this type of activity. Assessing the ability to perform actions that require rapid decision making, special motor and cognitive skills, it is necessary to take into account the general condition of the patient and the profile of adverse effects of eptifibatide.

    Form release / dosage:

    Solution for intravenous administration 0.75 mg / ml, 2 mg / ml.

    Packaging:

    Solution for intravenous administration at a concentration of 0.75 mg / ml per 100 ml in a vial or solution for intravenous administration at a concentration of 2 mg / ml of 10 ml per bottle of clear, colorless glass (type I, Hept. F.), sealed with a rubber stopper and An aluminum cap covered with a snap-off plastic lid.

    A 100 ml bottle is equipped with a device for hanging a vial made of polyethylene.

    1 bottle with instructions for use in a pack of cardboard.

    Storage conditions:

    In the original packaging at a temperature of 2 to 8 ° C in a dark place. Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date stated on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N013344 / 01
    Date of registration:22.04.2008
    The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia
    Manufacturer: & nbsp
    Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO
    Information update date: & nbsp13.11.2017
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