Composition, form of production and packaging
The solution for intravenous administration is transparent, dark green, with a weak characteristic odor.
radachlorin (the sum of the sodium salts of chlorin e6, chlorine p6, purpurin 5) 3.5 mg
[PRING] meglumine 0.2 g, water d / and up to 100 ml.
10 ml - bottles (1) - packs of cardboard.
10 ml - bottles (10) - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
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 Radachlorin to selectively accumulate in the skin tumor with its intravenous administration and generate singlet oxygen, which has a toxic effect on tumor cells and modifying the effect on their plasma membranes when exposed to light at a wavelength corresponding to one of the absorption peaks of the preparation (402, 502 , 532, 608 or 662 them). In the development of the effect after PDT with Radachlorin There are 3 stages:
Stage 1 - a characteristic reaction to light exposure in PDT, manifested in the form of edema and hyperemia of the irradiation zone of different severity;
Stage 2 - necrosis of the tumor, which is formed 2-4 days after the PDT session;
Stage 3 - rejection of necrotic masses and epithelization of the wound defect in 2-8 weeks, depending on the size of the tumor.
Radachlorin in doses of 0.5-2.4 mg / kg with irradiation of the tumor with laser radiation 3 hours after the administration of the drug does not have a mutagenic effect and does not damage the DIC of normal cells.
After a single intravenous administration of Radachlorin in doses of 0.5-2.4 mg / kg, it is distributed between blood and tissues for 0.5-5 hours. The concentration of Radachlorin in the blood serum reaches a maximum after 15-30 minutes and rapidly decreases, making after injection at a dose of 0.5 mg / kg after 1 hour - 10 Ојg / l, after 3 hours - 5 Ојg / l, after 24 hours - 1 mcg / l.
The concentration of Radachlorin in the tumor reaches a maximum after 1 hour (10-20 Ојg / ml), by, with a faster excretion of it from the surrounding healthy tissue, the maximum therapeutic index (contrast index) is observed 3 hours after the administration of the drug. The concentration of the drug in the tumor tissue is higher than in the surrounding healthy tissues, on average 3-6 times, depends on the morphological structure of the tumor, and is 2-10 Ојg / ml,
Rapid excretion of Radachlorin from blood, skin and mucous membranes and a high contrast index exclude damage to healthy organs and tissues and hypersensitivity of skin to daylight.
The highest levels of Radachlorin 3 hours after the administration are created in the liver, kidneys, tumor tissue.
About 70-80% Radachlorin is metabolized in the liver to biladienes (linear tetrapyrroles, which are also products of heme metabolism). The drug is excreted unchanged with faeces (15%) and urine (3%). Cumulative excretion Radachlorin with feces and urine in the first 12 hours is an average of 15-20% of the administered dose of the drug. The main part (98%) of Radachlorin is excreted or metabolized in the first 48 hours. Trace amounts of the drug are determined in the skin up to 6 days.
- fluorescent diagnosis of skin cancer;
- photodynamic therapy of superficial skin tumors (excluding melanoma).
The drug is administered once as an intravenous drip infusion for 30 minutes.
Light exposure to radiation with a wavelength of 662 В± 3 nm begins 3 hours after the end of the infusion. The optimal mode of exposure is the administration of the drug at a dose of 1.0-1.2 mg / kg and light exposure to radiation with a wavelength of 662 В± 3 nm at a dose of 300 J / cm 2 .
Subject to the possibility of re-treatment of patients with partial effect or stabilization, it is possible to use regimens 0.5-0.6 mg / kg - 300 J / cm 2 and 1.0-1.2 mg / kg-200 J / cm 2 . In this case, the choice of treatment should be carried out individually, taking into account the form and prevalence of the tumor process.
When exposed to a laser, remote surface irradiation is used through a quartz light guide with or without microlenses. As a source of laser radiation, a diode laser with a wavelength of 662 В± 3 nm is used.
To identify additional foci and clarify the boundaries of the tumor, it is recommended to combine the administration of radachlorin with fluorescent diagnostics, for example, using spectrofluorimeters. The intensity of fluorescence reaches a maximum 3 hours after the administration of the drug and is substantially higher for a dose of 1.2 mg / kg. The fluorescent contrast at the "tumor / norm" border varies within the limits of (2-4) / 1 (for a dose of 0.6 mg / kg) and (4-6) / 1 (for a dose of 1.2 mg / kg).
Preparation of a solution for intravenous infusion:
The contents of one or more vials are diluted in 200 ml of one of the following infusion solutions:
- 0.9% solution of sodium chloride;
- 5% or 10% solution of dextrose;
- 10% mannitol solution;
-4% or 8% potassium chloride solution;
To prepare the solution, do not use infusion solutions with an acidic pH.
With photodynamic therapy (PDT) with Radachlorin, the following are possible:
вЂў local reactions.
- Pain at the site of the irradiated focus during the entire procedure of PDT and up to 1 hour after PDT. The severity of the pain syndrome varies depending on the prevalence of the pathological process and the individual sensitivity of the patients;
- edema of surrounding tissues and soft tissues of the head, lasting 2-7 days.
For the relief of painful reactions, the use of analgesics is recommended.
вЂў On the skin:
rarely: itchy skin.
вЂў On the part of the hematopoiesis:
an increase in the absolute number of leukocytes in the peripheral blood can often be observed with an increase in the number of granulocytes.
- hypersensitivity to any of the components of the drug;
- Pregnancy and lactation;
- Children's age (experience of medical use in children is absent).
With caution: in persons with arterial hypertension, diabetes mellitus.
PREGNANCY AND LACTATION
Contraindicated in pregnancy. For the duration of treatment, breastfeeding should be discontinued.
APPLICATION FOR CHILDREN
Contraindicated in children.
Necrosis in the treatment zone usually begins to form in 2-4 days, and the rejection of the scab occurs in 2-8 weeks after exposure to the laser.
Precautions for use.
During laser exposure, the doctor and patient should wear protective goggles with a light filter that absorbs radiation 662 В± 3 nm.
The patient after the administration of Radachlorin should observe a limited light regime (avoid bright light) during the week.
Radachlorin should not be administered by the same syringe or through the same system for intravenous injections, through which other medications were administered.
Impact on the ability to drive vehicles and manage mechanisms
Direct contraindications to driving after a PDT session by Radachlorin have not been identified.
If any side effects occur, the question of driving and working with other mechanisms requires individual consideration.
Symptoms of overdose are similar to adverse side effects. Symptomatic and disintoxication therapy (symptomatic therapy according to indications, taking analgesics, antihistamines, antioxidants) is shown.
The incompatibility of Radachlorin with drugs that have an acid pH of the medium, for example, with ascorbic acid, has been revealed.
TERMS OF RELEASE FROM PHARMACY
TERMS AND CONDITIONS OF STORAGE
At temperatures from 0 to 8 В° C in a protected from light. The drug can be stored diluted at a temperature of 2 to 8 В° C not more than 24 hours before the introduction.The prepared solution is stable under room light or in daylight, however direct light exposure should be avoided. Keep out of the reach of children. Shelf life - 2.5 years.