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

Clinical and pharmacological group: & nbsp

Anticoagulants

Included in the formulation

Angioks®

lyophilizate in / in

Medicinz Company YuK Ltd. United Kingdom

АТХ:

B.01.A.E.06 Bivalirudin

Pharmacodynamics:

Bivalirudin is a selective direct thrombin inhibitor. It binds to the catalytic site of thrombin, as well as to the anion-binding site of both free and fibrin bound thrombin. Thrombin plays a major role in the thrombogenesis process, cleaving fibrinogen to form fibrin monomers and activating the clotting factor XIII to form an active clotting factor XIIIa, which promotes the formation of covalent cross-links between fibrin molecules, which leads to the formation of a stable thrombus. Thrombin also activates clotting factors V and VIII, promoting the further formation of thrombin, and activates platelets, stimulating aggregation and release of granules. Bivalirudin inhibits each of these thrombin effects.

With intravenous administration bivalirudin causes a measurable anticoagulant effect in a few minutes.

The binding of bivalirudin to thrombin is reversible.

Pharmacokinetics:

Pharmacokinetic parameters are linear.

Bioavailability of bivalirudin for intravenous administration is complete. Bivalirudin rapidly distributed between plasma and extracellular fluid. V_d in the equilibrium state is 0.1 l / kg. Bivalirudin does not bind to blood plasma proteins (with the exception of thrombin) or with erythrocytes. Metabolized by proteases, including thrombin. The half-life is 35-40 minutes. About 20% of bivalirudin is excreted unchanged in urine.

The pharmacokinetics of bivalirudin in patients with impaired liver function has not been studied, but it is assumed that it does not change because bivalirudin It is not metabolized with the participation of hepatic enzymes. Systemic clearance of bivalirudin decreases depending on the rate of glomerular filtration. Bivalirudin undergoes hemodialysis.

Indications:

As an anticoagulant in the course of transluminal coronary intervention, including when performing primary percutaneous transluminal coronary intervention in patients with acute myocardial infarction with ST segment elevation on the ECG.

With unstable angina or acute myocardial infarction without an increase in the ST segment with indications for urgent or early percutaneous transluminal coronary intervention.

ICD-10

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

IX.I20-I25.I21 Acute myocardial infarction

Contraindications:

Active bleeding or increased risk of bleeding due to congenital or acquired hemostasis disorders; severe uncontrolled hypertension; subacute bacterial endocarditis; severe renal failure (glomerular filtration rate <30 ml / min), including in patients on dialysis; children and adolescents under 18; hypersensitivity to bivalirudin; hypersensitivity to hirudin (to leeches).

Carefully:

Caution should be applied bivalirudin when conducting beta brachiotherapy, taking into account the cases of thrombosis during gamma-brachytherapy.

Pregnancy and lactation:

Do not use bivalirudin during pregnancy and lactation (breastfeeding), except when the expected benefit of therapy for the mother exceeds the possible risk to the fetus or infant.

It is not known whether bivalirudin with human breast milk.

Dosing and Administration:

Enter intravenously struino or drip. Do not administer intramuscularly.

In carrying out percutaneous transluminal coronary intervention injected intravenously in a dose of 750 μg / kg followed by immediate continuation of the infusion at a rate of 1.75 mg / kg / h until the end of the procedure. If necessary, administration of bivalirudin in the same dose can continue for another 4 hours after the end percutaneous transluminal coronary intervention, and then in the next 4-12 hours - at a dose of 250 μg / kg / h. After the percutaneous transluminal coronary intervention patients should be under constant supervision for the timely detection of symptoms of myocardial ischemia.

With unstable angina or acute myocardial infarction without an increase in the ST segment bivalirudin injected intravenously in a dose of 100 μg / kg followed by immediate infusion at a dose of 250 μg / kg / h for no more than 72 hours.

In the case of a planned percutaneous transluminal coronary intervention Before the procedure, additionally, bivalirudin in a dose of 500 mcg / kg followed by infusion at a dose of 1.75 mg / kg / h until the end of the procedure. After graduation percutaneous transluminal coronary intervention the administration can be continued for a further 4-12 hours at a dose of 250 μg / kg / h.

In patients with impaired renal function, the dose / rate of infusion should be adjusted.

Bivalirudin can be administered 30 minutes after the end of intravenous infusion of unfractionated heparin or 8 hours after subcutaneous injection of low molecular weight heparin.

Side effects:

From the coagulation system of the blood: very often - minor bleeding of various locations, bleeding at the site of the vascular puncture, hematoma at the puncture site c <5 cm in diameter; often significant bleeding of various locations (including fatal cases), thrombosis (including fatal cases), coronary stent thrombosis (including fatal cases), minor bleeding, bruising; infrequently - a hematoma at a puncture site with a diameter> 5 cm, an increase international normalized relationship, intracranial hemorrhage, coronary artery thrombosis, pericardial bleeding, retroperitoneal bleeding, vomiting of blood, gastrointestinal bleeding, melena, bleeding gums, pulmonary hemorrhage, pharyngeal bleeding, hemoptysis,nose bleed; rarely bleeding from the ear, esophageal hemorrhage, intraperitoneal bleeding, retroperitoneal hematoma

On the part of the hematopoiesis system: infrequently - thrombocytopenia, anemia.

From the cardiovascular system: infrequently - angina, ventricular tachycardia, bradycardia, lowering of arterial pressure, vascular anomalies; rarely - vascular pseudoaneurysm.

Allergic reactions: rarely - hives, rashes, anaphylactic reactions and shock.

Other: infrequently - nausea, shortness of breath, hematuria, headache, chest pain, back pain, pain in the groin, pain at the injection site, reperfusion injury (delayed reperfusion blood flow or lack thereof); rarely - reactions at the injection site.

Overdose:

There is no known antidote for bivalirudin, but its effect quickly disappears (the half-life is 35-40 minutes).

Interaction:

The combined use of bivalirudin with antiplatelet agents may be accompanied by an increased risk of hemorrhagic complications.

Special instructions:

Bivalirudin is recommended to be used simultaneously with acetylsalicylic acid and clopidogrel.

The effectiveness and safety of the exclusively jet infusion of bivalirudin has not been studied, therefore it is not recommended even for short-term procedures percutaneous transluminal coronary intervention.

Do not administer intramuscularly.

When bleeding symptoms appear, bivalirudin should be discontinued.

Instructions

Bivalirudin (Bivalirudinum)