Composition
Radachlorin is an 0.35% solution for intravenous administration. Radachlorin comes in 10-mg vials. Each vial contains 35 mg (1 mg/g) of active chlorine substance, i.e., sodium salt. Ten-gram vials are supplied in boxes with instructions enclosed. Boxes of 10 vials are provided with one instruction per box.

Indications
Radachlorin is applied to destroy malignant tumors of various origins. Radachlorin can be used both independently from and in combination with cytotoxic chemotherapy and radiotherapy to potentiate the therapeutic effect produced by them. Radachlorin also prevents implantation metastases due to its intraoperative effect on tissues.

Mechanism of Action
Radachlorin is a superpotent high-selective photosensitizer applied in photodynamic therapy (PDT). Radachlorin is rapidly (within a time span of 30 minutes to 5 hours) accumulated in malignant tumors. The contrast index ranges from 3 to 40, depending on the type of a tumor. Radachlorin is effective when excited by optical radiation at a wavelength of 662±5 nm. As a result, it starts to actively generate cytotoxic elements (such as singlet oxygen) in the tumor. Radachlorin is a high-cytophototoxic compound aimed at various types of tumor cells. Thus, it is considered to be able to prevent tumor growth. The absence of dark cytotoxicity and the rapid elimination of this compound from the skin of mucous membranes makes Radachlorin especially beneficial in PDT. The use of Radachlorin causes no damage to healthy organs or tissues, nor does it make skin hypersensitive to daylight. Compounds for chemotherapy and radiotherapy are able to potentiate the clinical effect produced by PDT. The results obtained in experiments carried out on animals showed that Radachlorin decreases the mobility of animals to some extent. However, other functional parts of the central nervous system were not affected.

Dosage and Application
The dose of Radachlorin introduced to patients (both children and adults) should range from 0.2 to 1.0 mg (the average is 0.65 mg) per 1 kg of the patient's weight per day. Radachlorin, an 0.35% solution for intravenous administration, is used to treat malignant tumors of the skin and oral mucosa of the III and IV stages, of the larynx, genital organs, mammary gland, digestive tract, lungs and bronchi, as well as endermic metastases and local tumor recurrences. Radachlorin is slowly administered intravenously just before a PDT session. Irradiation starts and ends within a time span of 2 to 5 hours after the administration of the compound. The patient is exposed to laser radiation at a dose of 200 to 500 J/cm?. The exposure time is 3 to 60 minutes.

There are 4 methods of laser irradiation. They are as follows:

• Remote superficial irradiation via a quartz lightguide with or without the use of microlenses.
• Endocavitary irradiation.
• Interstitial irradiation.
• The combination of superficial and interstitial kinds of irradiation.

In the 2nd, 3rd, and 4th cases, one may use various types of lightguides and diffusers. The patient is exposed to laser radiation at a dose of 150 to 600 J/cm?. In the case of interstitial irradiation, the radiation density ranges from 600 to 3,000 J/cm?.

Contraindications

Hypersensitivity to any component of the compound.

Precautions
After the use of Radachlorin, the patient should not be exposed to bright light (especially, daylight) within 12 hours. Furthermore, he or she should prevent their eyes from bright light within the following 12 hours. It is also recommended that the patient should avoid watching TV during first hours after the use of the compound. No experiments have been carried out during pregnancy. Radachlorin, like any other drugs, should not be used during pregnancy, especially in the early months of pregnancy, unless it is doubtless that the expected benefit for a mother stands higher than the potential risk of her expected child.

Side Effects
In some cases, injections of Radachlorin may raise the patient's temperature to 37.0°C to 38.5°С in 20 to 30 minutes or make him or her feel feverish. These side effects usually disappear within 30 minutes. To prevent these effects, one should take antipyretic, analgetic, and antihistaminic compounds. It was also reported that skin becomes hypersensitive to radiation after the intravenous administration of Radachlorin.

Overdosage
Currently, there is not much information on Radachlorin overdosage. Experiments on animals showed that LD10 totals 119 mg per kg, which exceeds the recommended dosage by a factor of 100 to 500. Intoxication causes severe cardiopulmonary decompensation. In the case of overdosage, one should undergo a corresponding symptomatic supporting therapy.

Storage Conditions
Radachlorin for intravenous administration should be kept in a cool dark place. Radachlorin solutions for injections in corresponding liquids for intravenous administration are resistant under indoor illumination or daylight within at least 24 hours. Thus, when administered through a dropper tube, the solution should not be necessarily shielded from scattered light. However, one should avoid immediate light directed at it. Radachlorin for intravenous administration should not be injected with the same syringe or through the same dropper tube which were used for administration of other compounds. Vials with Radachlorin should not be autoclaved.

Compatibility with Other Liquids for Intravenous Administration
Radachlorin for intravenous administration should be mixed with recommended solutions only, such as:

• 0.9% sodium chloride for intravenous administration,
• 5% glucose for intravenous injections,
• 10% mannitol for intravenous injections,
• Ringer's solution for intravenous administration,
• 0.3% potassium chloride and 0.9% sodium chloride for intravenous administration,
• 0.3% potassium chloride and 5% glucose for intravenous administration.

In accordance with pharmaceutical rules, Radachlorin solutions for intravenous administration should be prepared immediately before their introduction or kept at a temperature of 2 to 8°C for not more than 24 hours prior to the introduction.

Drug Compatibility
It has been proven that Radachlorin is incompatible with compounds having an acid pH factor (such as ascorbic acid).

Pharmakokinetics and Metabolism in Experiments on Animals
Thirty minutes after the intravenous administration at a dose of 20 mg/kg, Radachlorin shows a maximum concentration in the tumor (up to 0.3 mM) and remains there for up to 5 hours. The contrast index of accumulation becomes at a maximum after 3 hours. For superficial tumors, it is 3 for tumor/muscular tissue and 4 for tumor/skin. After 24 hours, the compound is eliminated from the body by 98 per cent (the semi-elimination period is 12 hours). Radachlorin is eliminated mainly from the body due to liver metabolism. Less than 2% of the administered dose goes out unchanged with urina. Protein-binding reaches 90 to 95%.