RADACHLORIN® SOLUTION FOR INTRAVENOUS INFUSION
MINISTRY OF HEALTH OF RUSSIAN FEDERATION
INSTRUCTION
on the medical use of the drug
RADACHLORIN®
Registration number: ЛС-001868
Trade mark: Radachlorin®
Drug form: concentrate for preparation of solution for intravenous infusion
Compound:
Active substance:
«Radachlorin®» – 5,00 g (what correspond to a set of sodium salts of
chlorine е6, chlorine р6, purpurine 5 – 0,35 g).
Excipients:
methyl glucamine – 0,20 g,
water for injections – till 100 ml.
Description: Transparent dark green liquid with a weak character smell.
Pharmacotherapeutical group: photosensitizer.
Code АТХ: L01XD.
Pharmacologic properties
Pharmacodynamics.
Radachlorin® is the photosensitizer of the second level for fluorescent diagnostics and photodynamic therapy of malignant tumors. The PDT is based on Radachlorin® ability to selectively accumulate in skin tumours after it’s intravenous infusion and to generate singlet oxygen which has a toxic effect on tumour’s cells and modifying effect to their plasmatic membranes during laser exposure with definite wave length, which corresponds to one of the peaks of drug absorption (402, 502, 532, 608 or 662 nm).
There are 3 stages of Radachlorin®-based PDT effect:
1 stage – character reaction to light exposure during PDT as edema and hyperemia of zone of exposure with different intensity;
2 stage – tumor necrosis, which forms 2-4 days after PDT procedure;
3 stage – rejection of necrotic masses and epithelization of the wound during 2-8 weeks after PDT (depending on tumor size).
Radachlorin® at a dose 0,5-2,4 mg/kg in combination with laser exposure of tumor 3 hours after infusion doesn’t have a mutagenous effect and doesn’t injure DNA of normal cells.
Pharmacokinetics.
After the unitary infusion of Radachlorin® at a dose 0,5-2,4 mg/kg the photosensitizer allocates between blood and tissues during 0,5-5 hours. The concentration of Radachlorin® in blood serum reaches maximum in 15-30 minutes after the infusion and quickly decreases, being after infusion in dose 0,5 mg/kg, in 1 hour – 10 mkg/l, in 3 hours – 5 mkg/l, in 24 hours – 1 mkg/l.
Radachlorin® concentration in the tumor reaches its maximum in 1 hour after the infusion (10-20 mkg/ml), however in conditions of its quicker elimination from healthy tissues surrounding the tumor, maximum therapeutical index (contrast index) is observed in 3 hours after the drug infusion. The concentration of the drug in tumor tissue is higher, than in normal tissues, on average in 3-6 times (2-10 mkg/ml) and depends on morphologic structure of the tumor.
Quick elimination of Radachlorin® from the blood, skin and mucous covers and high contrast index exclude the damage of normal organs and tissues and hypersensitivity of skin to daylight. The highest level of Radachlorin® in 3 hours after the infusion is in liver, kidneys, tumor tissue.
About 70-80% of Radachlorin® is metabolized in liver up to biladiens (linear tetrapyrrols, which are also produced as a result of hem metabolism). The part of drug eliminates unchanged with excrement (15%) and urine (3%). Cumulative excretion of Radachlorin® with excrements and urine during first 12 hours is 15-20% of the infused dose of the drug. The main part (98%) of Radachlorin® is eliminated or metabolized during first 48 hours. The trace quantity of the drug is discovered in the skin till 6 days.
Indications
• Fluorescent diagnostics of skin cancer.
• Photodynamic therapy of superficial skin tumours (except melanoma).
• Photodynamic therapy of precancerous (CIN I-III, erosion) and cancerous (carcinoma in situ) pathology of cervix uteri.
Contraindications
• Hypersensitivity to any component of the drug
• Pregnancy and lactation period
• Childhood (no test of the preparation has been run on children)
Use with caution if the patient has arterial hypertension, diabetes.
Dosage and Application
The drug should be infused once using an instillator during 30 minutes. Light irradiation with wave length 662+/-3 nm should be started in 3 hours after the end of the infusion. The optimal condition is drug dosage 1,0-1,2 mg/kg and light exposure with wave length 662+/-3 nm and light density 300 J/cm2.
If the recurrent procedure is possible for curing patients with partial effect or stabilization, two other conditions can be used: 0,5-0,6 mg/kg – 300 J/cm2; 1,0-1,2 mg/kg – 200 J/cm2. The choice of the condition should be made, taking into account the form and the prevalence of tumor process.
The laser exposure should be distant and superficial and made with quartz optical fiber with or without micro lenses with diameter of light spot from 2,5 to 3,0 cm for PDT of precancerous and cancerous cervix uteri pathology. The diode laser with wave length 662+/-3 nm should be used as a source of laser radiation.
To detect extra tumor focuses and to adjust the tumor borders it is highly recommended to combine Radachlorin® infusion with fluorescent diagnostics (for example, using spectrafluorimeters). The intensity of fluorescence reaches maximum level in 3 hours after the drug infusion and is much higher for the dose 1,2 mg/kg. Fluorescent contrast on the «tumor/normal skin» border is varied from (2-4)/1 (for the dose 0,6 mg/kg) and (4-6)/1 (for the dose 1,2 mg/kg).
Preparation of the solution for intravenous infusion
The content of one or some vials should be diluted in 200 ml of one of the next solutions:
• 0,9% sodium chloride for intravenous infusion
• 5% or 10% dextrose for intravenous infusion
• 10% mannitol for intravenous infusion
• Ringer's solution for intravenous infusion
• 4% or 8% KCl solution
It has been proven that Radachlorin® is incompatible with compounds having an acid pH factor (such as ascorbic acid). Compounds with acid pH factors should not be used for preparation of the solution for intravenous infusion.
Precautions.
During laser exposure the doctor and the patient should use protective glasses with light-filter, which absorb the radiation with wave length 662+/-3 nm.
The patient should avoid bright sunlight during 1 week after Radachlorin® infusion.
Radachlorin® should not be infused by syringe of instillator, which were used for infusion of other drugs.
Overdosage.
The symptoms of overdosage are similar to unfavorable. In case of overdosage symptomatic and detoxicating therapy should be carried out (infusion therapy, analgetics, antihistamines, antioxidants).
Side effects. During PDT with Radachlorin® the following side effects are possible:
• Local reactions. Often:
- The pain in the place of laser exposure during the PDT procedure and 1 hour after it. The intensity of pain syndrome is varied
depending on prevalence of pathologic process and individual sensitivity of the patient:
- The edema of surrounding tissues and soft head tissues, lasting from 2 to 7 days.
To cut off the pain syndrome analgesics should be used.
• Side effects for skin
rarely: skin itch.
• Blood side effects for hematopoiesis,
often: after PDT with Radachlorin® there can be increase of absolute quantity of leucocytes in peripheral blood with increase of granulocytes.
Drug interaction. It has been proven that Radachlorin® is incompatible with compounds having an acid pH factor (such as ascorbic acid). Appliance during pregnancy and lactation period.
PDT is contraindicative during pregnancy. During the treatment the lactation should be interrupted.
Influence to ability to drive a car and to operate different mechanisms. There are no contraindications to drive a car after PDT with Radachlorin® nowadays. If any side effects appear, the situation should be considered individually.Special indications. The necrosis in the zone of treatment begins to firm in 2-4 days, and the rejection of the scab takes place in 2-8 weeks after the laser exposure.
Shelf life. 2,5 years.
Do not use after the expiry date specified on package.
Storage conditions.
Radachlorin® should be kept in cool, dark place by the temperature from 0 to 8°С. The drug may be kept diluted no longer than 24 hours before the infusion by the temperature 2-8°С. The ready solution is steady in conditions of day light, but straight light should be avoided.
Keep in inaccessible for children place.
Terms of dispending in pharmacy. Radachlorin® is sold on medical prescription.
Manufacturer.
1. Federal State Establishment «Russian cardiologic scientific-industrial complex» of Ministry of Health and Social Development of the Russian Federation – Experimental Factory of Medicobiological Drugs (FSE «RCSIC» of Ministry of Health of Russian Federation - EFMBD), 121552, buildings 24,25,48, 15-a, 3-rd Cherepkovskaya street, Moscow, Tel./fax (499) 149-02-13.
2. Regional State Unitary Enterprise «Chelyabinsk regional hemotransfusion station» 454076, 68, Vorovskoy str., Chelyabinsk Tel./fax +7 (351) 232-78-90.
The holder of the certificate of registration / the enterprise,
taking complaints from consumers
«Rada-Pharma» LtD.
109316, 42, block 5, Volgogradskiy Prospekt, Moscow.
Tel./fax: +7-495-980-13-05