1. The Photoditazine Chlorin-Series Photosensitizer – Intravenous Solution
Pharmaceutical Form and Package
Photoditazine (Fotoditazin™) is a 0.50 % dark-green solution with a yellow tint for intravenous administration. Photoditazine comes in 10-ml dark-brown glass vials singly in a cardboard box with instruction enclosed. Each vial contains 50 mg (5.0 mg/ml) of active agent (in the form of N-dimethyl-glucamine salt of chlorin e6) diluted in 10 ml of water for injections.
Indications
Photoditazine is used to destroy malignant tumors of various origins. Photoditazine can be used both independently from and in combination with cytotoxic chemotherapy and radiotherapy to increase the therapeutic effect produced by them. Photoditazine also prevents implantation metastases formation arising from an intraoperative action onto tissues. It is a highly informative diagnostic drug for spectral fluorescent methods of analysis of malignant tumors.
Pharmacodynamics
Photoditazine is a photosensitizer of the second generation. It is aimed at fluorescent diagnostics (FD) and photodynamic therapy (PDT) of malignant tumors. The medicine is selectively accumulated in malignant tumors. Irradiation with monochromic light at a wavelength of 661 – 662 nm delivered to the tumor produces a photosensitizing effect which includes generation of active forms of oxygen (singlet oxygen) in tumor tissues and generation of other free radicals which lead to the development of biochemical and structure functional changes in tumor cells and their death. High phototoxicity of Photoditazine is characteristic for different types of tumor cells.
One of the important features of Photoditazine is the absence of dark toxicity, rapid (within 24 – 28 hours) elimination from the body – first of all, from skin and mucosae, high affinity (i.e. ratio of concentrations of the medicine in a tumor and healthy tissues which reaches, depending on the type of a tumor, maximum values – over 20). Due to the features of the medicine given above, a damaging effect produced by light onto healthy organs and tissues, as well as skin lesions produced by light, can be practically excluded during PDT.
Pharmacokinetics
After intravenous injection of Photoditazine, its maximum concentration in a tumor is achieved 1.0 – 1.5 hours later (depending on a nosological type of a tumor). 4 – 5 hours later the concentration of Photoditazine in a tumor will be gradually decreasing. The period of semi-elimination of the medicine makes 12 hours. 28 hours after the intravenous injection, trace quantities of the medicine can be found in blood. Maximum ratio of contrast of the medicine accumulation (a tumor/normal tissue) depends on a nosological type of a tumor and can range from 3.0 to 24. The medicine is being actively metabolized in liver (more than 95 %). The protein bond makes up 92 – 96 %.
Contraindications
High sensitivity to the medicine.
Significant renal and hepatic failure.
Cardiovascular diseases at the decompensation stage.
Pregnancy and nursing time.
Pediatric use.
Method of Administration and Dosage
Photoditazine is injected in a single-shot manner by means of intravenous drop infusion within 30 minutes at a dose of 0.7 – 1.4 mg/kg of the patient’s body weight. 1 – 1.5 hours after the medicine injection, a session of local irradiation of a tumor is performed at a dose of 150 – 600 J/cm2 at a radiation power density of 150 – 300 mW/cm2. The light dose and the radiation power are set depending on the localization and size of a tumor, and its nosological nature.
The PDT session is performed with the help of laser devices which generate radiation at a wavelength of 661 – 662 nm.
Solution Preparation for Intravenous Infusion
A calculated dose of Photoditazine is dissolved in 100 ml of normal saline.
Side Effects
The body temperature rise (up to 37 – 38°C) within 30 minutes and a presence of pains in the area of irradiation which can be stopped by intake of analgesics and antihistamines.
The blood pressure boost in patients with the accompanying cardiovascular diseases.
Overdosage
Symptoms: anhelation; tachycardia; blood pressure boost; excitation being changed to depression; hypothermia.
Treatment: symptomatic therapy (there is no a specific antidote).
Compatibility with Other Medicines
It is possible to use Photoditazine together with analgesics.
It is not recommended to use local anesthetic drugs (infiltration anesthesia).
Precautions
Within 24 hours after the medicine injection, a patient should strictly follow light regime (it is prohibited to be exposed to direct sunlight, to watch TV programs, etc.).
Right from the first day of using Photoditazine, sun blocking creams should be used to protect open skin areas.
Storage Conditions
Photoditazine should be stored at a temperature from 0 to +10°C in a dark place, out of the reach of children.
Shelf Life
12 months from manufacture date printed on the package.
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