Angiox (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Medicines Company UK Ltd. (Great Britain)

ATC Code

B01AE06 (Bivalirudin)

Active Substance

Bivalirudin (Rec.INN registered by WHO)

Dosage Form

Angiox

Lyophilizate for the preparation of solution for intravenous administration 250 mg: vial. 10 pcs.

Dosage Form, Packaging, and Composition

250 mg – vials (10) – carton packs.

Clinical-Pharmacological Group

Anticoagulant. Direct thrombin inhibitor

Pharmacotherapeutic Group

Direct thrombin inhibitor

Pharmacological Action

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 key role in the thrombus formation process by cleaving fibrinogen to form fibrin monomers and activating coagulation factor XIII to form active coagulation factor XIIIa, which promotes the formation of covalent cross-links between fibrin molecules, leading to the formation of a stable thrombus.

Thrombin also activates coagulation factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release. Bivalirudin inhibits each of these effects of thrombin.

Following intravenous administration, Bivalirudin produces a measurable anticoagulant effect within minutes.

The binding of bivalirudin to thrombin is reversible.

Pharmacokinetics

The pharmacokinetic parameters are linear.

The bioavailability of bivalirudin after intravenous administration is complete. Bivalirudin is rapidly distributed between plasma and extracellular fluid. The steady-state Vd is 0.1 L/kg. Bivalirudin does not bind to plasma proteins (except for thrombin) or to red blood cells.

It is metabolized by proteases, including thrombin. T_1/2 is 35-40 minutes. Approximately 20% of bivalirudin is excreted unchanged in the urine.

The pharmacokinetics of bivalirudin in patients with impaired liver function has not been studied, but it is assumed not to change since Bivalirudin is not metabolized by hepatic enzymes.

The systemic clearance of bivalirudin decreases depending on the glomerular filtration rate. Bivalirudin is hemodialyzable.

Indications

As an anticoagulant during percutaneous transluminal coronary intervention (PCI), including during primary PCI in patients with acute ST-segment elevation myocardial infarction.

For unstable angina or acute myocardial infarction without ST-segment elevation when urgent or early PCI is indicated.

ICD codes

Dosage Regimen

Administered intravenously as a bolus or infusion. Do not administer intramuscularly.

During PCI, administer as an intravenous bolus at a dose of 750 mcg/kg, followed immediately by a continuous infusion at a rate of 1.75 mg/kg/h until the procedure is completed.

If necessary, administration of bivalirudin at the same dose may be continued for up to 4 hours after the completion of PCI, and then at a dose of 250 mcg/kg/h for the subsequent 4-12 hours. After PCI, patients should be under constant observation for the timely detection of myocardial ischemia symptoms.

For unstable angina or acute myocardial infarction without ST-segment elevation, Bivalirudin is administered as an intravenous bolus at a dose of 100 mcg/kg, followed immediately by an infusion at a dose of 250 mcg/kg/h for no more than 72 hours.

In case of a planned PCI, an additional bolus of Bivalirudin at a dose of 500 mcg/kg is administered before the procedure, followed by an infusion at a dose of 1.75 mg/kg/h until the procedure is completed. After the completion of PCI, administration can be continued for the subsequent 4-12 hours at a dose of 250 mcg/kg/h.

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

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

Adverse Reactions

From the blood coagulation system very common – minor bleeding of various locations, bleeding at the vascular puncture site, hematoma at the puncture site with a diameter < 5 cm; common – major bleeding of various locations (including fatal cases), thrombosis (including fatal cases), coronary stent thrombosis (including fatal cases), minor bleeding, bruising; uncommon – hematoma at the puncture site with a diameter > 5 cm, increased INR, intracranial bleeding, coronary artery thrombosis, pericardial bleeding, retroperitoneal bleeding, hematemesis, gastrointestinal bleeding, melena, gum bleeding, pulmonary bleeding, pharyngeal bleeding, hemoptysis, epistaxis; rare – ear bleeding, esophageal bleeding, intraperitoneal bleeding, retroperitoneal hematoma.

From the hematopoietic system uncommon – thrombocytopenia, anemia.

From the cardiovascular system uncommon – angina pectoris, ventricular tachycardia, bradycardia, decreased blood pressure, vascular anomalies; rare – vascular pseudoaneurysm.

Allergic reactions rare – urticaria, rash, anaphylactic reactions and shock.

Other uncommon – nausea, dyspnea, hematuria, headache, chest pain, back pain, groin pain, injection site pain, reperfusion injury (slow or no-reflow reperfusion); rare – reactions at the site of administration.

Contraindications

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

Use in Pregnancy and Lactation

Bivalirudin should not be used during pregnancy and lactation (breastfeeding) except in cases where the expected therapeutic benefit for the mother outweighs the potential risk to the fetus or breastfed infant.

It is not known whether Bivalirudin is excreted in human breast milk.

Use in Renal Impairment

Contraindicated: severe renal failure (GFR < 30 ml/min), including patients on dialysis.

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

Pediatric Use

Contraindication: children and adolescents under 18 years of age;

Special Precautions

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

Bivalirudin should be used with caution during beta-brachytherapy, considering cases of thrombosis during gamma-brachytherapy.

The efficacy and safety of bivalirudin administration by bolus injection only has not been studied; therefore, it is not recommended even for short-term PCI procedures.

Do not administer intramuscularly.

If symptoms of bleeding appear, administration of bivalirudin should be discontinued.

Drug Interactions

Concomitant use of bivalirudin with antiplatelet agents may be associated with an increased risk of hemorrhagic complications.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.