Integrilin
Integrilin: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Integrilin
ATX code: B01AC16
Active ingredient: eptifibatide (eptifibatide)
Manufacturer: Glaxo Operations UK Limited (UK)
Description and photo update: 28.11.2018
Prices in pharmacies: from 3777 rubles.
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Integrilin is an antiplatelet agent.
Release form and composition
Dosage form - solution for intravenous (i / v) administration: colorless, transparent (0.75 mg / ml - 100 ml in glass bottles, in a cardboard box 1 bottle; 2 mg / ml - 10 ml in glass bottles, cardboard box 1 bottle; each pack also contains instructions for the use of Integrilin).
Composition of 1 ml solution:
- active substance: eptifibatide - 0.75 mg or 2 mg;
- auxiliary components: water for injection, sodium hydroxide, citric acid monohydrate.
Pharmacological properties
Pharmacodynamics
The active component of Integrilin - eptifibatide, is a synthetic cyclic heptapeptide that contains 6 amino acid residues, including one cysteinamide and one mercaptopropionyl residue - desaminocysteinyl.
Eptifibatide is a platelet aggregation inhibitor belonging to the arginine-glycine-aspartate-mimetic class. Integrilin reversibly inhibits platelet aggregation, thereby preventing binding to the glycoprotein IIb / IIIa receptors of platelets von Willebrand factor, fibrinogen and other adhesive ligands.
In an ex vivo model using adenosine diphosphate (ADP) and other agonists that induce platelet aggregation, the inhibition of aggregation by eptifibatid depended on the dose and concentration of Integrilin.
After bolus IV administration of Integrilin at a dose of 0.18 mg / kg, the effect develops immediately. Ex vivo, subsequent continuous iv infusion of the drug at a dose of 0.002 mg / kg / min provided more than 80% inhibition of ADP-induced platelet aggregation in more than 80% of patients with physiological calcium concentrations. The inhibition of platelet aggregation is reversible. 4 hours after the end of continuous intravenous infusion at a dose of 0.002 mg / kg / min, platelet function is restored to its initial level (more than 50%).
In patients with unstable angina pectoris and myocardial infarction without a Q wave, ex vivo measurements of ADP-induced platelet aggregation at physiological calcium concentrations [anticoagulant D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK)] showed concentration-dependent inhibition: 50 (concentration that inhibits aggregation by 50%) - 557 ng / ml, IC 80 (concentration that inhibits aggregation by 80%) - 1107 ng / ml.
During therapy, the bleeding time increases up to 5 times. Within 2-6 hours after the end of Integrilin administration, this indicator returns to the initial one.
Used as a monopreparation, eptifibatide does not significantly affect the activated partial thromboplastin time (APTT) and prothrombin time (PT).
Pharmacokinetics
With bolus doses of 0.09–0.25 mg / kg and infusion at a rate of 0.000 5–0.003 mg / kg / min, the pharmacokinetics of eptifibatide is linear and dose-dependent.
When infusing a dose of 0.002 mg / kg / min to patients with coronary heart disease, C ss (mean equilibrium concentration) in plasma is 0.001 5–0.002 2 mg / ml. This level is reached more quickly if Integrilin is given as a bolus dose of 0.18 mg / kg prior to infusion. Eptifibatid binds to plasma proteins by about 25%. Plasma clearance is 55–80 ml / kg / h. The volume of distribution (V d) is 185–260 ml / kg. The half-life (T ½) is about 2.5 hours.
The proportion of renal excretion of the total clearance in healthy volunteers is approximately 50%. About 50% of the drug is excreted unchanged.
With a decrease in creatinine clearance (CC), reduced body weight (<74 kg) and in elderly patients, there is a moderate increase in V d and T ½.
The pharmacokinetics of eptifibatide does not depend on the sex of the patient and the size of the dose used.
With mild renal impairment (CC ≥ 50 ml / min), dosage adjustment is not required. In moderate renal failure (CC 30-50 ml / min) and severe (CC <30 ml / min), the clearance of eptifibatide is approximately halved, C ss increases approximately 2-fold, and therefore the Integrilin dose is recommended to be reduced.
Indications for use
Integrilin is used in combination with acetylsalicylic acid and unfractionated heparin to prevent the following diseases / conditions in adults:
- myocardial infarction in patients with unstable angina pectoris or myocardial infarction without a Q wave, the last pain attack in whom was observed during the last 24 hours, in patients with changes in the electrocardiogram and / or increased activity of cardiospecific enzymes;
- sudden closure of blood vessels and associated acute ischemic complications during percutaneous transluminal coronary angioplasty (PTCA).
Contraindications
- severe arterial hypertension (systolic blood pressure> 200 mm Hg or diastolic> 110 mm Hg) against the background of antihypertensive therapy;
- prothrombin time> 1.2 times the control or MHO (international normalized ratio) ≥ 2;
- thrombocytopenia (<100,000 cells / mm 3);
- a history of hemorrhagic diathesis;
- a history of intracranial disease (neoplasm, arteriovenous malformation, aneurysm);
- acute disturbance of cerebral circulation within the last 30 days or a history of hemorrhagic stroke;
- serious urological / genital bleeding, gastric / intestinal bleeding and other severe pathological bleeding in the previous 30 days;
- severe trauma or major surgery in the previous 6 weeks;
- clinically significant hepatic impairment;
- severe renal failure (CC <30 ml / min);
- the need for hemodialysis;
- simultaneous or planned use of another inhibitor of glycoprotein IIb / IIIa receptors;
- age up to 18 years;
- lactation period;
- hypersensitivity to any component of Integrilin.
Carefully:
- simultaneous use of drugs that affect the hemostasis system: non-steroidal anti-inflammatory drugs, oral anticoagulants, thrombolytics, adenosine, dextran, prostacyclin, clopidogrel, ticlopidine, dipyridamole;
- combined intake of streptokinase in the treatment of acute myocardial infarction (due to an increased risk of bleeding);
- simultaneous administration of low molecular weight heparin;
- pregnancy (only if the benefits of therapy for the mother exceed the possible risks to the fetus).
Integrilin, instructions for use: method and dosage
Integrilin is administered intravenously. A solution for infusion of 0.75 mg / ml and a solution for bolus administration of 2 mg / ml are used together according to the instructions.
The simultaneous use of Integrilin and heparin is recommended, unless there are contraindications to the latter.
Integrilin solution is also used in conjunction with acetylsalicylic acid, which is a standard component of the treatment of acute coronary syndromes, unless there are contraindications.
Percutaneous coronary intervention (PCI)
Adult patients with CC ≥ 50 ml / min (according to the Cockcroft-Gault formula) are prescribed Integrilin IV bolus at a dose of 0.18 mg / kg immediately before PCI, another similar dose is administered 10 minutes later. Simultaneously with the first bolus, a continuous intravenous infusion of eptifibatide at a dose of 0.002 mg / kg / min is started and continued until the patient is transferred to outpatient treatment or for 18-24 hours after the manipulation, but not less than 12 hours.
The recommended dosing regimen for CC 30-50 ml / min: intravenous bolus at a dose of 0.18 mg / kg immediately before the onset of PCI, 10 minutes later another similar dose is administered as a bolus. Simultaneously with the first bolus, a continuous intravenous infusion of eptifibatide at a dose of 0.001 mg / kg / min is started and continued until the patient is transferred to outpatient treatment or for 18-24 hours after the manipulation, but not less than 12 hours.
Acute coronary syndrome (unstable angina or myocardial infarction without Q wave)
Adult patients with CC ≥ 50 ml / min are prescribed Integrilin IV bolus at a dose of 0.18 mg / kg as soon as possible after confirmation of the diagnosis, then a continuous infusion is started at a dose of 0.002 mg / kg / min and continued up to 72 hours before the operation. for aortic shunting or before the patient is discharged from the hospital (if the operation is not performed). If PTCA is performed during the treatment period, intravenous infusion is continued for another 20-24 hours after this manipulation. The maximum total duration of Integrilin administration can be 96 hours.
The recommended dosing regimen for CC 30-50 ml / min: intravenous bolus at a dose of 0.18 mg / kg as soon as possible after confirmation of the diagnosis, then immediately start a continuous infusion at a dose of 0.001 mg / kg / min and continue up to 72 hours until the beginning of aortic bypass surgery or before the patient is discharged from the hospital (if the operation is not performed). If PTCA is required, intravenous infusion is continued for another 20-24 hours after this manipulation. The maximum total duration of Integrilin administration can be 96 hours.
To calculate CC (ml / min), use the Cockcroft - Gault formula:
- men: (140 - age in years) × (actual body weight in kg) / 72 × (serum creatinine in mg / dL);
- women: (140 - age in years) × (actual body weight in kg) × (0.85) / 72 × (serum creatinine in mg / dL).
With a body weight of more than 121 kg, the patient is injected no more than 22.6 mg IV bolus, in the form of an IV infusion - no more than 15 mg / h (with a creatinine concentration <2 mg / dL) or 7.5 mg / h (at a creatine concentration of 2–4 mg / dl).
Planned and emergency surgery
With a planned operation, the Integrilin infusion should be discontinued beforehand so that platelet function is restored to normal levels.
If urgent cardiac surgery is required, the infusion is canceled.
Integrilin administration instructions
- Check the solution for foreign particles, discoloration, turbidity. In case of violation of transparency and homogeneity, the drug is prohibited to use. No light protection required.
- For bolus administration, draw the solution into a syringe from a 10 ml vial and inject intravenously in a stream for 1–2 minutes.
- The intravenous drip should be started immediately after the bolus. If there is a pump that regulates the infusion rate, Integrilin can be administered directly from a 100 ml bottle without dilution. The injection system must be vented. The needle for connecting the system to the vial is inserted strictly through the center of the stopper.
Integrilin solution can be administered in the same system with the following drugs: heparin, lidocaine, morphine, atropine sulfate, midazolam, metoprolol, verapamil, alteplase, nitroglycerin, pethidine, dobutamine.
Integrilin can also be administered in the same system with 0.9% sodium chloride solution or its mixture with 5% dextrose. When using any of these solvents, a content of up to 60 mmol / l of potassium chloride is allowed.
If any amount of the drug remains in the vial, it should be disposed of. It is not subject to further use.
Integrilin cannot be administered in the same system as furosemide.
Eptifibatide should not be mixed with drugs if their compatibility has not been reliably established.
Side effects
Most of the side effects of Integrilin are associated with the development of bleeding of varying intensity (especially during invasive procedures on the heart), disorders of the heart and cardiovascular system.
The undesirable disorders described below are classified as follows: very often - ≥ 1/10, often - ≥ 1/100 and <1/10, infrequently - ≥ 1/1000 and <1/100, rarely - ≥ 1/10 000 and <1/1000, very rarely - <1/10 000, including isolated cases. It is important to note that a causal relationship with the use of eptifibatide has not been established in all cases.
Clinical trial data:
- on the part of the blood and lymphatic system: bleeding (light and massive, including bleeding during coronary artery bypass grafting, gastrointestinal, genitourinary, intracranial, retroperitoneal, intraoral / oropharyngeal bleeding, reducing hematocrit / hemoglobin bleeding, as well as hematuria, hematemesis, etc.); infrequently - thrombocytopenia;
- from the side of the vessels: often - arterial hypotension, cardiogenic shock, phlebitis;
- from the heart: often - ventricular tachycardia, AV block, ventricular / atrial fibrillation, congestive heart failure, cardiac arrest;
- from the nervous system: infrequently - cerebral ischemia.
Post-registration data:
- on the part of the skin and subcutaneous tissues: very rarely - skin rashes, adverse events at the injection site (for example, urticaria);
- from the immune system: very rarely - anaphylactic reactions;
- on the part of the blood and lymphatic system: very rarely - hematoma, acute deep thrombocytopenia, pulmonary hemorrhage, fatal bleeding (mainly affecting the peripheral and central nervous system - intracranial bleeding, hemorrhagic stroke).
Overdose
Data on Integrilin overdose in humans are very limited.
Signs of serious events (both with bolus and rapid infusion) were not observed. Nine cases are known when the dose of Integrilin exceeded the recommended 2 times. None of the patients developed serious bleeding. One patient was after coronary artery bypass grafting - he had moderate bleeding. Intracranial bleeding was not recorded. Nevertheless, the risk of bleeding should not be excluded in case of an overdose of eptifibatide.
Integrilin activity decreases rapidly after discontinuation of intravenous infusion. To accelerate the elimination of the drug from the body, hemodialysis can be used. In some cases, a blood transfusion is advisable.
special instructions
The drug is always used only in a hospital setting.
Integrilin is always recommended to be used in conjunction with heparin, except in cases where there are contraindications to its use, for example, with a history of thrombocytopenia associated with taking heparin.
During therapy, all patients (especially women, elderly patients, patients with low body weight) should be carefully examined in order to identify possible signs of bleeding in time. If the developed bleeding cannot be stopped by applying a pressure bandage, it is necessary to urgently stop the administration of Integrilin and heparin.
In patients undergoing percutaneous transluminal coronary angioplasty, the likelihood of bleeding is greatest at the site of arterial access: the site of catheter insertion, venesection, venipuncture or arteriopuncture. These places should be monitored most closely. It is also necessary to monitor the patient's condition for retroperitoneal bleeding, bleeding from the genitourinary tract or gastrointestinal tract, possible bleeding of the central nervous system (central and peripheral nervous system).
If during PTCA a catheter is inserted into the femoral artery, it is necessary to make sure that only its anterior wall is punctured. It is allowed to remove the introducer only after the coagulation function is restored to normal (activated blood coagulation time - less than 180 seconds), usually this requires 2 to 6 hours after heparin discontinuation. After removal of the introducer, hemostasis is necessary, followed by careful observation of the patient, up to discharge from the hospital.
Integrilin inhibits platelet aggregation, but does not affect their viability. According to post-registration observations, in rare cases, immune thrombocytopenia develops. If the patient's plasma contains factors that can bind to eptifibatide and glycoprotein IIb / IIIa receptors, the development of an immune thrombocytopenic response is possible with repeated use of eptifibatide, as well as with the first use of inhibitors of glycoprotein IIb / IIIa receptors. In this regard, it is recommended to exercise caution and control possible signs of thrombocytopenia, accompanied by arterial hypotension and / or other symptoms of hypersensitivity.
If the platelet count drops to less than 100,000 / mm 3, or an acute deep thrombocytopenia develops, it is necessary to urgently consider discontinuing any drugs that may have a thrombocytopenic effect (including eptifibatide, heparin, clopidogrel), start supportive therapy under the control of the platelet count and conduct examination. If the development of thrombocytopenia is not associated with the appointment of Integrilin, after normalization of the platelet count, it is possible to resume therapy.
Integrilin increases bleeding time up to 5 times. This disorder is reversible after discontinuation of the infusion, the indicators return to the initial level within 2–6 hours. When Integrilin was used as a monopreparation, no significant effect on APTT and prothrombin time was noted.
In case of unstable angina pectoris or myocardial infarction without a Q wave, the following doses are more preferable for patients weighing 70 kg or more: bolus - 5000 U, continuous infusion - 1000 U / h. For patients weighing up to 70 kg: bolus dose - 60 U / kg, subsequent infusion - 12 U / kg / h. The APTT should be monitored so that the values are in the range of 50 to 70 s.
When performing PTCA, it is necessary to control the activated coagulation time (ABC) so that its values are in the range from 300 to 350 s. In the case of an increase in the indicator of more than 300 s, the use of heparin is discontinued (its resumption is possible only after a decrease in the value of less than 300 s).
If within 6 hours prior to intracoronary stenting with non-emergency PTCA heparin was not administered, a bolus IV heparin in a dose of 60 U / kg is recommended. The target ABC during the intervention is 200–300 s. During PTCA, an additional bolus of heparin is possible in order to maintain the ABC in this range.
During the period of application of Integrilin, it is possible to change laboratory parameters characterizing bleeding. There were no significant differences (compared with placebo) in such indicators as renal function (concentration of serum creatinine, blood urea nitrogen), liver function (concentration of aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase), platelet count, hematocrit, hemoglobin.
Influence on the ability to drive vehicles and complex mechanisms
Studies on the effect of eptifibatide on human cognitive and motor functions have not been conducted. Integrilin's safety profile indicates no negative impact on the ability to concentrate and reaction speed.
Application during pregnancy and lactation
In pregnant women, studies on the use of Integrilin have not been conducted. In studies on rabbits and rats using doses that exceed those recommended for humans by 4 and 8 times, respectively, signs of impaired fertility and a negative effect on fetal development were not observed. However, the results of animal studies are not considered sufficient to predict possible reactions in humans. Therefore, during pregnancy, Integrilin is used only if the expected benefit from therapy for the mother exceeds the possible risks to the fetus.
It is not known whether eptifibatide penetrates into breast milk. For the period of treatment, it is recommended to stop breastfeeding.
Pediatric use
Integrilin is not used in pediatrics.
With impaired renal function
In mild renal impairment (CC ≥ 50 ml / min), patients with unstable angina pectoris and myocardial infarction without a Q wave (requiring PTCA or not) are prescribed Integrilin in standard doses.
For patients with moderate renal dysfunction (CC 30-50 ml / min), the dose of Integrilin during infusion is reduced to 0.001 mg / kg / min.
Clinical data on the use of the drug in severe renal impairment (CC <30 ml / min) and in patients requiring hemodialysis are insufficient, therefore Integrilin is contraindicated in this category of patients.
For violations of liver function
The drug is contraindicated in clinically significant liver failure.
Caution should be prescribed in case of impaired liver function, since the clinical experience of using Integrilin in this category of patients is very limited (the effect of the drug on blood clotting is possible).
Use in the elderly
Integrilin should be used with caution in elderly patients due to the increased risk of bleeding.
Drug interactions
An increase in the risk of bleeding with the simultaneous use of warfarin and dipyridamole is not observed, as in patients with prothrombin time ≥ 14.5 seconds.
In clinical studies, it was found that Integrilin may increase the risk of bleeding in patients with acute myocardial infarction in the case of simultaneous use of streptokinase. The risk of bleeding, including massive, increases in patients with acute myocardial infarction with ST-segment elevation with the combined use of low doses of tenecteplase.
Integrilin is incompatible with furosemide.
Special studies on the drug interaction of eptifibatide with other drugs have not been conducted. In clinical studies, interaction reactions were not identified with the simultaneous use of the following drugs, which are often used in patients with cardiovascular diseases: furosemide, nifedipine, atropine, fentanyl, diazepam, lisinopril, warfarin, heparin, diltiazem, morphine, enalapril, captopril, metoprolol, midazolam, lidocaine, digoxin, atenolol, diphenhydramine, cefazolin, amlodipine, nitrates.
Analogs
Integrilin analogues are: Aggregal, Agrenox, Antagrex, Aspirin Cardio, Brilinta, Detromb, Zylt, Cardiomagnyl, Cardogrel, Clopigrant, Clopidogrel, Lirta, Monafram, Plavix, Trombex, Fluder, Egitromb, Effient and others.
Terms and conditions of storage
Store in its original packaging at a temperature of 2-8 ° C out of the reach of children and protected from light.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews of Integrilin
There are no reviews on Integrilin on forums and medical websites that would allow assessing the degree of effectiveness and tolerability of the drug. This is probably due to the fact that eptifibatid is always used in a hospital setting and only as part of a combination therapy.
Integrilin price in pharmacies
The approximate prices for Integrilin are: 2 mg / ml - 3500–3845 rubles for a 10 ml bottle, 0.75 mg / ml - 10,500-13,500 rubles for a 100 ml bottle.
Integrilin: prices in online pharmacies
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Drug name Price Pharmacy |
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Integrilin solution for intravenous injection 2mg / ml 10ml RUB 3777 Buy |
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Integrilin 2 mg / ml solution for intravenous administration 10 ml 1 pc. RUB 3777 Buy |
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Integrilin 0.75 mg / ml solution for intravenous administration 100 ml 1 pc. 12694 RUB Buy |
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
