Radachlorine^® (Solution, Concentrate) Instructions for Use

ATC Code

L01XD (Sensitizing agents used for photodynamic/radiation therapy)

Clinical-Pharmacological Group

Photosensitizing drug

Pharmacotherapeutic Group

Photosensitizing agent

Pharmacological Action

Radachlorin is a second-generation photosensitizer intended for fluorescent diagnosis (FD) and photodynamic therapy (PDT) of malignant tumors.

The PDT method is based on the ability of Radachlorine^® to selectively accumulate in a skin tumor upon its intravenous administration and to generate singlet oxygen, which has a toxic effect on tumor cells and a modifying effect on their plasma membranes when exposed to light with a wavelength corresponding to one of the absorption peaks of the drug (402, 502, 532, 608, or 662 nm).

The development of the effect after PDT with Radachlorin can be divided into 3 stages.

Stage 1 – a characteristic reaction to light exposure during PDT, manifested as edema and hyperemia of the irradiation zone of varying severity.

Stage 2 – tumor necrosis, which forms 2-4 days after the PDT session.

Stage 3 – rejection of necrotic masses and epithelialization of the wound defect after 2-8 weeks depending on the size of the tumor.

Radachlorin in doses of 0.5-2.4 mg/kg when irradiating the tumor with laser radiation 3 hours after drug administration does not have a mutagenic effect and does not damage the DNA of normal cells.

Pharmacokinetics

After a single intravenous administration of Radachlorine^® in doses of 0.5-2.4 mg/kg, it distributes between blood and tissues within 0.5-5 hours.

The concentration of Radachlorine^® in blood serum reaches a maximum after 15-30 minutes and decreases rapidly, amounting to 10 µg/L 1 hour after administration of a 0.5 mg/kg dose, 5 µg/L after 3 hours, and 1 µg/L after 24 hours.

The concentration of Radachlorine^® in the tumor reaches a maximum after 1 hour (10-20 µg/ml), but, due to its faster elimination from the healthy tissues surrounding the tumor, the maximum therapeutic index (contrast index) is observed 3 hours after drug administration.

The concentration of the drug in tumor tissue is higher than in surrounding healthy tissues, on average by 3-6 times, depends on the morphological structure of the tumor, and is 2-10 µg/ml.

Rapid elimination of Radachlorine^® from blood, skin, and mucous membranes and a high contrast index preclude damage to healthy organs and tissues and hypersensitivity of the skin to daylight.

The highest levels of Radachlorine^® 3 hours after administration are achieved in the liver, kidneys, and tumor tissue.

About 70-80% of Radachlorin is metabolized in the liver to biladienes (linear tetrapyrroles, which are also metabolites of heme). The drug is excreted unchanged in feces (15%) and urine (3%).

The cumulative excretion of Radachlorine^® with feces and urine during the first 12 hours averages 15-20% of the administered drug dose. The main part (98%) of Radachlorine^® is excreted or metabolized within the first 48 hours. Trace amounts of the drug are detected in the skin for up to 6 days.

Indications

• Fluorescent diagnosis of skin cancer;
• Photodynamic therapy of superficial skin tumors (excluding melanoma).

ICD codes

Dosage Regimen

Concentrate

It is administered once as an intravenous drip infusion over 30 minutes.

Light exposure with radiation at a wavelength of 662±3 nm is started 3 hours after the end of the infusion.

The optimal exposure regimen is administration of the drug at a dose of 1-1.2 mg/kg and light exposure with radiation at a wavelength of 662±3 nm at a dose of 300 J/cm².

Provided that repeated treatment of patients with partial effect or stabilization is possible, 2 other regimens can also be used: 0.5-0.6 mg/kg – 300 J/cm²; 1-1.2 mg/kg – 200 J/cm².

The choice of regimen should be made individually, taking into account the form and prevalence of the tumor process.

When using a laser, remote superficial irradiation through a quartz light guide with or without microlenses is used.

A diode laser with a wavelength of 662±3 nm is used as a source of laser radiation.

To identify additional foci and clarify the boundaries of the tumor focus spread, it is recommended to combine the administration of Radachlorine^® with fluorescent diagnosis, for example, using spectrofluorimeters.

The fluorescence intensity reaches a maximum 3 hours after drug administration and is significantly higher for the 1.2 mg/kg dose. The fluorescent contrast at the tumor/normal border varies within (2÷4)/1 (for the 0.6 mg/kg dose) and (4÷6)/1 (for the 1.2 mg/kg dose).

Solution

The drug is administered once as an intravenous drip infusion over 30 minutes.

Light exposure with radiation at a wavelength of 662±3 nm is started 3 hours after the end of the infusion.

The optimal exposure regimen is administration of the drug at a dose of 1.0-1.2 mg/kg and light exposure with radiation at a wavelength of 662±3 nm at a dose of 300 J/cm².

Provided that repeated treatment of patients with partial effect or stabilization is possible, the following regimens can be used: 0.5-0.6 mg/kg – 300 J/cm² and 1.0-1.2 mg/kg – 200 J/cm².

The choice of regimen should be made individually, taking into account the form and prevalence of the tumor process.

When using a laser, remote superficial irradiation through a quartz light guide with or without microlenses is used. A diode laser with a wavelength of 662±3 nm is used as a source of laser radiation.

To identify additional foci and clarify the boundaries of the tumor focus spread, it is recommended to combine the administration of Radachlorine^® with fluorescent diagnosis, for example, using spectrofluorimeters.

The fluorescence intensity reaches a maximum 3 hours after drug administration and is significantly higher for the 1.2 mg/kg dose. The fluorescent contrast at the “tumor/normal” border varies within (2÷4)/1 (for the 0.6 mg/kg dose) and (4÷6)/1 (for the 1.2 mg/kg dose).

Preparation of the solution for intravenous infusion

The contents of one or several vials are diluted in 200 ml of one of the following infusion solutions:

• 0.9% sodium chloride solution;
• 5% or 10% dextrose solution;
• 10% mannitol solution;
• Ringer’s solution;
• 4% or 8% potassium chloride solution;

Infusion solutions with an acidic pH should not be used to prepare the solution.

Adverse Reactions

During photodynamic therapy (PDT) with Radachlorine^®, the following are possible:

• Local reactions.

Often:

• Pain at the site of the irradiated focus throughout the entire PDT procedure and up to 1 hour after PDT. The severity of the pain syndrome varies depending on the prevalence of the pathological process and individual sensitivity of patients;
• Edema of surrounding tissues and soft tissues of the head, lasting 2-7 days.

Analgesics are recommended to relieve pain reactions.

• From the skin

Rarely: skin itching.

• From the hematopoietic organs

An increase in the absolute number of leukocytes in the peripheral blood with an increase in the number of granulocytes can often be observed.

Contraindications

• Hypersensitivity to any of the components of the drug;
• Pregnancy and lactation;
• Childhood (experience of medical use in children is absent).

With caution in persons with arterial hypertension, diabetes mellitus.

Use in Pregnancy and Lactation

Contraindicated during pregnancy. Breastfeeding should be discontinued during treatment.

Pediatric Use

Contraindicated in children.

Special Precautions

Necrosis in the treatment area usually begins to form after 2-4 days, and scab rejection occurs 2-8 weeks after laser exposure.

Precautions for use.

During laser exposure, the doctor and the patient must use protective goggles with a light filter that absorbs radiation of 662 ±3 nm.

After administration of Radachlorine^®, the patient must observe a restricted light regimen (avoid bright light) for one week.

Radachlorin should not be administered with the same syringe or through the same intravenous administration system through which other drugs were administered.

Effect on the ability to drive vehicles and mechanisms

No direct contraindications to driving a car after a PDT session with Radachlorine^® have currently been identified.

If any side effects occur, the issue of driving vehicles and working with other mechanisms requires individual consideration.

Overdose

Symptoms of overdose are similar to adverse side reactions. Symptomatic and detoxification therapy is indicated (infusion therapy as indicated, administration of analgesics, antihistamines, antioxidants).

Drug Interactions

Incompatibility of Radachlorine^® with drugs having an acidic pH environment, for example, with ascorbic acid, has been identified.

Storage Conditions

At a temperature from 0 to 8°C (46.4°F) protected from light. The drug can be stored diluted at a temperature from 2 to 8°C (46.4°F) for no more than 24 hours before the start of administration. The prepared solution is stable under room lighting or daylight conditions; however, direct light exposure should be avoided. Keep out of reach of children.

Shelf Life

Shelf life – 2.5 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.