Indocyanine Zelenyi (Lyophilisate) Instructions for Use

ATC Code

V04CX01 (Indocyanine green)

Active Substance

Indocyanine green (USP)

Clinical-Pharmacological Group

Diagnostic agent. Fluorescent dye

Pharmacotherapeutic Group

Diagnostic agent

Pharmacological Action

Indocyanine green has a distinct absorption maximum in the infrared region at 800 nm in blood plasma or blood. The emission maximum during fluorescence measurement is at 830 nm, and the optical density of oxyhemoglobin and reduced hemoglobin in the blood is equal at this wavelength. Consequently, it is possible to determine the concentration of indocyanine green in whole blood, plasma, and serum, regardless of the oxygen saturation level.

Pharmacokinetics

Distribution

After intravenous administration, Indocyanine green does not distribute to the liver, kidneys, or lungs. It does not cross the placenta. It is not detected in urine or cerebrospinal fluid. After entering the bloodstream, indocyanine green rapidly binds to plasma proteins, with 95% being transported by β-apolipoprotein B.

Metabolism

It is not metabolized.

Excretion

The elimination of indocyanine green from blood plasma occurs in two phases. The half-life in the first phase is 3-4 minutes, and in the second phase, it is 60-80 minutes. It is excreted almost exclusively by parenchymal liver cells at a rate of about 0.1 mg/min/kg with bile in an unmetabolized, unbound form. The maximum concentration in bile is observed 0.5-2 hours after administration and depends on the amount of indocyanine green administered.

Indications

Indocyanine green-Pulsion is used for diagnostic purposes.

Diagnosis of circulatory disorders, including microcirculation

• Measurement of minute cardiac output and stroke volume;
• Measurement of circulating blood volume;
• Measurement of cerebral blood flow.

Diagnosis of liver functions

• Measurement of liver blood flow;
• Measurement of liver excretory function.

Ophthalmic angiography

• Measurement of choroidal blood flow.

ICD codes

Dosage Regimen

Lyophilisate

Intravenously

Before use, the contents of the vial are dissolved in water for injections. Add 5 ml of water for injections to the vial with a dosage of 25 mg, and add 10 ml of water for injections to the vial with a dosage of 50 mg. The prepared solution contains 5 mg/ml of indocyanine green. For cardiovascular, circulatory, and microcirculatory diagnostics, the drug is administered intravenously at a dose of 0.1 to 0.3 mg/kg of body weight.

For diagnostics of liver function, the drug is administered intravenously at a dose of 0.25 to 0.5 mg/kg of body weight.

For measurement of choroidal blood flow, the drug is administered intravenously at a dose of 0.1 to 0.3 mg/kg of body weight.

Daily dose

• adults, elderly patients, children from 11 years – not more than 5 mg/kg of body weight;
• children from 2 to 11 years – not more than 2.5 mg/kg of body weight;
• children from 0 to 2 years– not more than 1.25 mg/kg of body weight.

Adverse Reactions

Allergic reactions, spasms of the coronary arteries.

In patients with renal insufficiency, feelings of anxiety, sensation of heat, nausea, itching, urticaria, tachycardia, decreased blood pressure, bronchospasm, laryngospasm, “flushes,” facial edema may be observed. Simultaneously with anaphylactic reactions, eosinophilia may occur.

In case of anaphylactic reactions, the following actions should be taken

• Stop the administration of the drug, leave the catheter or cannula in the vein;
• Clear the airways, quickly administer 100-300 ml of hydrocortisone or other glucocorticosteroids intravenously;
• Ensure adequate lung ventilation and monitor the function of the cardiovascular system;
• Administer antihistamine drugs intravenously slowly.

Necessary actions in case of anaphylactic shock

• Place the patient in a horizontal position with legs raised up;
• Quickly restore the volume of circulating fluid (e.g., administer 0.9% sodium chloride solution or plasma-substituting solution);
• Quickly administer 0.1-0.5 mg of epinephrine diluted in 10 ml of 0.9% sodium chloride solution intravenously (repeat administration every 10 minutes if necessary).

Contraindications

• Hypersensitivity to indocyanine green or to sodium iodide;
• Hypersensitivity to iodine;
• In hyperthyroidism, in autonomous adenomas of the thyroid gland;
• In hyperbilirubinemia in newborns and premature infants;
• In previously identified intolerance to the drug, as there is a risk of developing anaphylactic reactions.

With caution: in patients daily using beta-adrenergic blockers; in patients with severe renal insufficiency (creatinine clearance < 10 ml/min) may be used only after a benefit/risk assessment.

Use in Pregnancy and Lactation

No negative impact on the course of pregnancy or fetal development was found when indocyanine green was used in 242 pregnant women.

Studies on the effect on reproductive function, teratogenic and carcinogenic effects have not been conducted. No potential risk of impact on the human body has been identified.

The drug should not be used in pregnant women, except in cases where the intended benefit to the mother from its use outweighs the potential risk to the fetus and such a study is conducted by a doctor out of necessity.

Data on the penetration of the drug into milk are absent; however, if it is necessary to use the drug during breastfeeding, breastfeeding should be discontinued.

Use in Renal Impairment

In patients with severe renal impairment (creatinine clearance < 10 ml/min), it may be used only after a benefit/risk assessment.

Pediatric Use

Can be used according to indications following the dosing regimen.

Special Precautions

Do not use other solvents containing salts (Ringer’s solution, 0.9% sodium chloride solution, etc.), as they lead to precipitation!

Thyroid studies using radioactive iodine should be performed in patients no earlier than 7 days after the use of indocyanine green, as the sodium iodide contained in the drug may affect the results of thyroid studies.

When administering the drug, avoid its entry into the surrounding tissues.

In case of the drug solution entering the surrounding tissues, immediately stop the administration and provide analgesia.

Effect on the ability to drive vehicles, mechanisms

There are no data on the effect on the ability to perform potentially hazardous activities requiring special attention and quick reactions (driving a car and other vehicles, etc.).

Drug Interactions

Not compatible with other solvents except water for injections. Probenecid and its metabolites reduce the secretion of indocyanine green, which may affect the study results.

Absorption is reduced with simultaneous use of injectable forms of drugs containing sodium bisulfite (especially in combinations with heparin).

Drugs and substances that may reduce absorption: trimeperidine, methadone, morphine and other narcotic analgesics; as well as anticonvulsants, bisulfites, haloperidol, metamizole sodium, phenobarbital, phenylbutazone.

Drugs and substances that may increase absorption: cyclopropane, probenecid, rifampicin.

Storage Conditions

In a place protected from light at a temperature not exceeding 30°C (86°F). Keep out of reach of children. The vial and the prepared solution are protected from light exposure.

Shelf Life

Shelf life – 3 years.

Dispensing Status

By prescription.

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.