Monophramus - instructions for use, doses, side effects, contraindications

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Dosage form: & nbspsolution for intravenous administration

Composition:

Active ingredient: antibodies of monoclonal FRaMon F (ab ')₂ fragments of 5 mg.

Excipients: sodium chloride 8.78 mg; sodium hydrogen phosphate dihydrate 1.64 mg; sodium dihydrogen phosphate dihydrate 0.11 mg; water for injection up to 1 ml.

Description:

Transparent colorless liquid.

Characteristic. The monofram is a F (ab ')₂ fragments of mouse monoclonal antibodies FRaMon (Framon) against the platelet fibrinogen receptor - GP IIb-IIIa (αIIbβ3-integrin).

Pharmacotherapeutic group:Antiaggregant agent

ATX: & nbsp

Inhibitors of platelet aggregation (excluding heparin)

Pharmacodynamics:

Monaphram refers to antiaggregants - inhibitors of platelet aggregation. By the mechanism of action, it is a glycoprotein antagonist (GP) IIb-IIIa. Monafram prevents GP interaction IIb-IIIa with fibrinogen and other ligands, and thus inhibits platelet aggregation. With intravenous bolus administration at a dose of 0.25 mg / kg body weight, monafram in most patients (more than 90%) completely inhibits platelet aggregation activity after 1 hour, as measured by their ability to ADP-induced aggregation. During the first days, aggregation activity of platelets remains reduced by more than 70%, and after 3 days - by approximately 40%.The ability of platelets to aggregate is completely restored 6 days after the administration of the drug. Platelet-associated Monaphram 1 hour after administration occupies at least 95% of GP IIb-IIIa on the surface of circulating platelets. In the first day, more than 70% are left occupied, 40-50% after 3 days, and less than 20% of GP after 6 days IIb-IIIa. The degree of inhibition of aggregation correlates with the amount blocked by the preparation of GP molecules IIb-IIIa

In patients with ischemic heart disease who underwent coronary angioplasty with a high risk of thrombotic complications, Monafram reduced the number of adverse outcomes more than 3 times (from 11% to 3%) (death from cardiovascular causes, myocardial infarction, indications for repeated revascularization) within 1 month after the angioplasty. The comparison group consisted of patients who did not receive Monafram and other GP IIb-IIIa antagonists. In primary angioplasty of patients with acute coronary syndrome without ST segment elevation, Monaphram reduced the number of adverse outcomes within 1 month by more than 2.5 times (from 19% to 7%).

Pharmacokinetics:

Free, present in plasma Monophram is completely excreted from the blood stream for 12 hours, and associated with platelets 6-8 days after administration.

Indications:Prevention of acute and subacute thrombosis in coronary angioplasty in patients with ischemic heart disease. The use of monophram is most indicated in angioplasty with an increased risk of thrombotic complications, including in patients with acute coronary syndrome, complicated coronary artery disease (lesion of the left main coronary artery, one or more stenoses of type C, multivessel lesions), and insufficient basic antiplatelet therapy (most often due to late onset of administration and / or low dose of thienopyridines).

Contraindications:

Conditions characterized by an increased risk of hemorrhagic complications:

(1) active internal bleeding, including the recent - up to 6 weeks;

(2) disorders of cerebral circulation in the last 2 years of life, previously suffered hemorrhagic stroke;

(3) major surgery or trauma in the last 2 months;

(4) hemorrhagic diathesis;

(5) thrombocytopenia (less than 100,000 / μl);

(6) intracranial neoplasms, arteriovenous fistula or vascular aneurysm, intracranial hematomas;

(7) vasculitis;

(8) uncontrolled arterial hypertension (systolic pressure> 180 mm Hg or diastolic pressure> 110 mm Hg);

(9) hypertensive or diabetic retinopathy;

(10) puncture of uncompressed vessels;

(11) clinically significant anemia;

(12) suspected aortic aneurysm stratification;

(13) traumatic cardiopulmonary resuscitation.

Dosing and Administration:

The drug is administered intravenously in the form of a bolus injection at a dose of 0.25 mg / kg body weight. The required dose is diluted with 10-20 ml of 0.9% sodium chloride solution and administered intravenously for 3-5 minutes for 10-30 minutes before angioplasty.

Monaphram can not be used in case of violation of ampoule / vial integrity, turbidity, appearance of sediment and insoluble particles. When taking the drug from ampoules / vials and subsequent manipulations, avoid foaming the solution.

Side effects:

Thrombocytopenia. After the administration of monophram, thrombocytopenia with a decrease in the number of platelets below 50,000 / μL was observed in 3-4% of patients, and below 20,000 / mm3 in less than 1% of patients.In these situations, transfusion of platelet mass is recommended to reduce the risk of possible bleeding. The number of platelets usually normalizes within 3-5 days. The use of Monaframa can also be accompanied by a slight (by 10-30%) decrease in the number of platelets within the first 3 days after administration, which is clinically not dangerous.

Bleeding. The use of monaphram can be accompanied by the appearance of subcutaneous hematomas at the sites of vascular puncture and slight bleeding gums. There is also a risk of major bleeding and significant changes in the quantitative composition of red blood (erythrocytes, hemoglobin, hematocrit). Similar, dangerous hemorrhagic complications were observed in less than 0.5% of cases. In these situations, it is recommended to transfuse plasma-substituting solutions, and, if necessary, blood components.

To prevent bleeding when using Monaframa, the following precautions are recommended: (1) to prefer radial access during angioplasty; (2) when using femoral access, avoid puncturing the posterior artery wall, remove the access device no later,than 6 hours after the procedure with the activated clotting time (ABC) less than 175 seconds, and press the access site for at least 30 minutes; (3) one day before and within the first two days after the administration of Monaframa, avoid endoscopic procedures, probing, puncture of the cavities, as well as subcutaneous and intramuscular injections (if necessary, special care must be taken).

Allergic reactions. None of the patients had any signs of an allergy to the introduction of Monaphram. Nevertheless, it is impossible to exclude the possibility of developing allergic reactions, including anaphylactic shock.

Development of antibodies. The frequency of production of antibodies against Monaphram is about 5%. Their formation is not associated with the development of allergic reactions and other clinically expressed side effects.

Overdose:

Repeated use

There is experience of safe repeated administration of the drug. Before repeated use, it is recommended that a test be performed for the presence of antibodies against Monaphram in the plasma / serum.

Interaction:

Heparin. Heparin is administered before the start of coronary angioplasty in the form of a bolus at a dose of 0.06 U / g, but in total - no more than 5000 units.ABC is supported in the range from 200 to 300 seconds. ABC is measured every 30 minutes and with ABC less than 200 seconds, a bolus of heparin is administered (at 0.02 U / g) until ABC is greater than 200 seconds. After the angioplasty, the administration of heparin ceases.

Acetylsalicylic acid. Monaphram, like other antagonists of GP IIb-IIIa, is usually used against a background of acetylsalicylic acid (75-325 mg / day).

Tienopyridines (ticlopidine and clopidogrel). The expediency of the use of thienopyridines (primarily clopidogrel) in combination with antagonists of GP IIb-IIIa. It is advisable to plan the appointment of thienopyridines in such a way that their action develops no later than 2-3 days after the administration of Monaphram, i.e. against the background of a decrease in the antiplatelet effect of the latter. In primary angioplasty of patients with acute coronary syndrome, Monaphram is usually used against a background of high loading doses of clopidogrel (300-600 mg on the first day) and subsequent application of standard doses (75-150 mg / day). The experience of combined use of thienopyridines and antagonists of GP IIb-IIIa, including Monaframa, shows that their joint use does not lead to undesirable side effects and, in particular, to the development of hemorrhagic syndrome.

Thrombolytics. Expediency and safety of thrombolytics in combination with antagonists of GP IIb-IIIa and, including with Monaphram, remains unclear. If there is a need for combined use of Monaphram and thrombolytics, an increased risk of hemorrhagic complications must be considered.

Indirect anticoagulants. Expediency - and safety of the use of indirect anticoagulants in combination with GP antagonists IIb-IIIaand, including with Monaphram, remains unexplored. In the event that Monophramus is used against the background of indirect anticoagulants, it is necessary to take into account the increased risk of hemorrhagic complications.

Special instructions:When using Monaphram it is necessary: to determine the content of platelets before the introduction of the drug and then to conduct repeated determinations 2-3 hours later, 8 and 24 hours after the administration, to make measurements of hemocoagulant parameters to detect possible hemostasis disorders, to ensure the availability of platelet mass for possible transfusion.

Form release / dosage:Solution for intravenous administration - 5 mg.

Packaging:Vials or ampoules of 1 ml.For 2 or 5 vials or ampoules in a contour acheikova package, a contour mesh package in a cardboard box with instructions for medical use. For 2 or 5 bottles with instructions for use in a pack of cardboard with cells.

Storage conditions:In dry, protected from light and out of reach of children at a temperature of 2 to 10 ° C. Do not freeze.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N003348 / 02

Date of registration:08.05.2009 / 19.02.2018

Expiration Date:Unlimited

The owner of the registration certificate:FRAMON, CJSC FRAMON, CJSC Russia

Manufacturer: & nbsp

GU Russian Cardiology Research and Production Complex MH RF - branch Experimental production of medico-biological preparations Russia

Information update date: & nbsp13.06.2018

Illustrated instructions

Instructions

Monaphram (Monafram)