Abciximab - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Antiaggregants

Included in the formulation

ReoPro®

solution in / in

Eli Lilly East SA Switzerland

АТХ:

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

B.01.A.C.13 Abciximab

Pharmacodynamics:

Pharmacological action - antithrombotic, antianginal. Fab fragment of chimeric human / mouse monoclonal antibodies 7E3.

The drug causes conformational changes in the arginine-glycine-asparaginate-binding site of the receptor and prevents the fixation of fibrinogen, vWF and other adhesive molecules with the activated GPIIb / IIIa glycoprotein complex on the platelet membrane, disrupting the final stage of platelet aggregation.

Pharmacokinetics:

The initial half-life is 10 minutes, the half-life of the second phase is 30 minutes. Presumably, it is catabolized, like all other proteins.

With IV introduction, a constant concentration of abciximab in the plasma is maintained only under the condition of continuous infusion, and after it stops falling for 6 hours quickly, and then slowly, for 10 days, which is due to the presence of a fraction associated with platelets. In / in the bolus administration leads to the inhibition of ADP-induced platelet aggregation. Two hours after the administration of high doses, more than 80% of the GPIIb / IIIa receptors are blocked.The average time of bleeding increases to 30 or more minutes. After cessation of infusion, aggregation normalizes after 48 hours, bleeding time after 24 hours.

Indications:

- prevention of myocardial ischemia in patients at high risk for whom percutaneous coronary balloon angioplasty is planned, stent implantation or atherectomy (as part of combination therapy with heparin and acetylsalicylic acid);

- propensity to thrombosis, including acute myocardial infarction with Q-wave;

- unstable angina (in patients not responding to conventional therapy), if coronary angioplasty is planned in the next 24 hours;

- postinfarction angina, ischemic stroke, thrombosis of peripheral arteries in combination with heparin;

- condition after angioplasty of the coronary arteries or atherectomy for the prevention of acute cardiac ischemic complications in patients with a high risk of reocclusion of the operated vessel (presence of an intracoronary thrombus, the extent of damage is more than 20 mm).

ICD-10

IX.I20-I25.I20.0 Unstable angina

IX.I20-I25.I20 Angina pectoris [angina pectoris]

IX.I20-I25.I25.2 Postponed myocardial infarction

IX.I20-I25.I21.9 Acute myocardial infarction, unspecified

IX.I20-I25.I21 Acute myocardial infarction

IX.I80-I89.I82 Embolism and thrombosis of other veins

IX.I80-I89.I80 Phlebitis and thrombophlebitis

Contraindications:

hypersensitivity;

aneurysm of large vessels;

- malformations of arteries / veins;

- internal bleeding, recent (in the last 6 weeks) clinically significant bleeding in the digestive tract or genitourinary system;

- disorders of cerebral circulation (in the anamnesis for the last 2 years), residual phenomena after cerebrovascular accident with neurological deficit;

- hemorrhagic vasculitis;

- Arterial hypertension (the crisis current);

- intracranial neoplasm, extensive surgery or trauma (including recent ones - within the last 6 weeks);

- thrombocytopenia (less than 100 000 / μl);

- breast-feeding, children's age;

- Retinopathy (diabetic or hypertensive);

- marked violations of the liver or kidneys.

Carefully:

- with diseases of the digestive tract in history;

- when taking anticoagulants inside during the preceding 7 days;

- with intravenous dextran before coronary angioplasty;

- if there is a history of percutaneous coronary intervention (failed, lasting more than 70 minutes, within 12 hours after the development of acute myocardial infarction);

- during pregnancy;

- with a body weight of less than 75 kg ;,

- when the patient is over 65 years of age.

Pregnancy and lactation:

The action category for fetus by FDA is C.

When pregnancy is used only in cases where the expected benefit for the mother exceeds the risk to the fetus.

If it is necessary to use lactation, breastfeeding should be discontinued.

Dosing and Administration:

The recommended dose is 0.25 mg / kg IV in the form of a bolus. The scheme of administration depends on the indications and the clinical situation.

In myocardial infarction with ST segment elevation: bolus 0.25 mg / kg, then for 12 hours 0.125 μg / (kg × min) in combination with alteplase and heparin.

With unstable angina, a bolus administration in a similar dose (followed by infusion for 12 hours) is started 24 hours before the planned angioplasty.

In coronary angioplasty: 10 minutes before the intervention, 0.25 mg / kg (duration of the bolus injection is at least 1 minute), then infusion at a rate of 10 μg / min for 12 hours (using a continuous infusion pump equipped with built-in sterile pyrogen-free,weakly binding proteins with a 0.2 / 0.22 micron filter).

Side effects:

From the side of the cardiovascular system: possible bleeding (the next 36 hours after administration), arterial hypotension, bradycardia, pulmonary edema, AV-blockade III degree, supraventricular tachycardia, ventricular tachyarrhythmias, pericardial effusion, peripheral vascular thromboembolism, intermittent claudication, pulmonary embolism.

From the digestive system: nausea, vomiting, diarrhea, constipation, ileus.

From the side of the central nervous system and peripheral nervous system: confusion, dizziness, brain ischemia, insomnia, hypoesthesia.

From the musculoskeletal system: myopathy, myalgia.

From the urinary system: renal failure (aggravation and development), urinary retention.

On the part of the hematopoiesis system: thrombocytopenia, anemia, leukopenia, leukocytosis.

From the respiratory system: pleural effusion, pneumonia.

Allergic reactions: itching, anaphylactic shock.

Other: petechia, cellulite, dysphonia, phlegmon, visual impairment.

Overdose:When an overdose is observed profuse bleeding, vascular collapse, thrombocytopenia. Treatment - the introduction of platelet mass.

Interaction:

In combination with anticoagulants, thrombolytic agents, heparin, antiplatelet agents (acetylsalicylic acid, ticlopidine, dipyridamole, dextrans, diclofenac, ibuprofen, indomethacin, ketoprofen, ketorolac, clopidogrel, meloxicam and other drugs) - an increased risk of bleeding.

The introduction of other monoclonal antibodies increases the risk of allergic reactions.

Special instructions:

In connection with the high probability of bleeding, it is necessary that the introduction of abciximab be carried out by trained personnel in a specialized hospital.

Before the introduction of abciximab, the number of platelets, prothrombin time, APTT should be determined. The determination of Hb and hematocrit as well as the ECG are carried out before, 12 hours and 24 hours after the bolus injection. BP and pulse are monitored every hour during the first 4 hours after the bolus injection, and then 6, 12, 18, 24 hours after it. In case of serious bleeding, which does not stop clamping, the administration should be discontinued.

Increases the possibility of bleeding at the site of arterial access to the femoral artery.For vascular access puncture only the front wall of the artery or vein. The use of the method of end-to-end approaches for determining the vascular structure is not recommended.

Avoid unnecessary puncture of the arteries, veins, intravenous injections, bladder catheterization, nasotracheal intubation, the introduction of the nasogastric tube, the imposition of an automatic blood pressure cuff. When receiving venous access, incompressible areas (subclavian or jugular vein) should be avoided. The puncture points of the vessels must be documented and kept under observation. When removing the dressings, be extra careful. To prevent spontaneous bleeding from the gastrointestinal tract - the appointment of H2-histamine receptor blockers or liquid antacids; vomiting - antiemetic drugs.

The drug must be syringed using a 0.2 or 0.22 micron filter with a low level of protein binding to reduce the likelihood of thrombocytopenia due to the presence of protein impurities. When heavy bleeding occurs with a drop in bcc and uncontrolled hypotension, an allergic reaction and thrombocytopenia, the treatment is stopped and the platelet is poured.

Coagulation potential is monitored by determining the activated clotting time at the level of 300-350 s, every 15-30 minutes during the entire angioplasty procedure. Simultaneously, the level of hemoglobin, hematocrit, platelet count, PT (platelet count) at the beginning and every 12 hours before removal of catheters are recorded. In the future, each of these indicators should be determined daily until a period of steady improvement or discharge from the hospital. Inguinal areas should be examined twice a day to identify signs of hematoma formation, the appearance of new vascular noise, or bleeding.

Patients over 70 years of age or body weight less than 75 kg require more careful monitoring for early detection of signs of bleeding or other method of correction of hemostasis (increased tendency to severe bleeding).

Instructions

Abciximab (Abciximabum)