Photosens^® (Concentrate) Instructions for Use

Marketing Authorization Holder

State Scientific Center “NIOPIK”, FSUE (Russia)

ATC Code

L01XD (Sensitizing agents used for photodynamic/radiation therapy)

Dosage Form

Photosens®

Concentrate for solution for infusion 2 mg/1 ml: 20 ml or 50 ml fl., 50 ml bt.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion as a dark blue solution with a greenish tint, odorless.

* calculated as the dry substance.

Excipients: water for injections – up to 1 ml.

20 ml – colorless glass flasks (1) – cardboard packs.
50 ml – colorless glass flasks (1) – cardboard packs.
50 ml – glass bottles for blood and blood substitutes (1) – cardboard packs.

Clinical-Pharmacological Group

Photosensitizing drug

Pharmacotherapeutic Group

Photosensitizing agent

Pharmacological Action

Photosens^® is a second-generation synthetic photosensitizer for fluorescent diagnosis and photodynamic therapy (PDT) of malignant tumors.

The PDT method is based on the ability of the drug to selectively accumulate in the tumor upon its intravenous administration and, upon exposure to light with a wavelength corresponding to the absorption peak of the photosensitizer (676 nm), to generate singlet oxygen and other active radicals that have a toxic effect on tumor cells.

The effectiveness of photodynamic damage to a sensitized cell is determined by the intracellular concentration (accumulation level) of the sensitizer; its localization in the cell and photochemical activity (quantum yield of singlet oxygen or free radical generation); the applied light dose of laser irradiation and the method of its delivery.

In addition to the direct cytotoxic effect on tumor cells during PDT, an important role in destruction is played by the disruption of blood supply due to damage to the endothelium of the blood vessels of the tumor tissue and cytokine reactions caused by stimulation of tumor necrosis factor production, activation of macrophages, leukocytes, and lymphocytes.

Three phases can be distinguished in the drug’s action: Phase 1 – a characteristic reaction to light exposure during PDT, manifested as edema and hyperemia of the irradiation zone of varying severity; Phase 2 – tumor necrosis, which forms on days 2-7 after the PDT session; Phase 3 – rejection of necrotic masses and epithelialization of the wound defect within 2-4 weeks depending on the tumor size.

Data from morphological studies confirm that 24 hours after laser exposure, zones of damage are clearly defined in the tumor, in which autolysis phenomena are observed.

Hydroxyaluminium trisulfophthalocyanine in doses of 0.5-2 mg/kg does not possess mutagenic or DNA-damaging effects, and does not cause significant changes in homeostasis parameters (biochemical parameters of blood serum, blood cell composition, and immune status parameters).

Pharmacokinetics

After a single intravenous administration at doses of 0.8 and 0.5 mg/kg, it is distributed throughout the body sufficiently quickly.

The decrease in the drug concentration in blood serum during the first day after administration is biphasic (a faster decrease in the first 6 hours and a slower one over the next 18 hours).

The concentration in the blood 5 minutes and 6 hours after administration is 9 and 1 µg/ml, respectively, and after 24 hours it decreases to 0.5-0.1 µg/ml.

A further decrease in the drug concentration occurs very slowly, and in trace amounts (0.01 µg/ml and less) it is detected up to 8 weeks after administration.

The highest concentrations are achieved in the liver, tumor tissue, lymph nodes, stomach, peritoneum, adipose tissue, heart, mucous membranes, and skin.

The concentration of the drug in tumor tissue is on average 1.5-1.8 times higher than in the surrounding healthy tissues.

When administered at doses of 0.8 and 0.5 mg/kg, C_max in the tumor and skin is reached within the first 1-2 days, and then slowly decreases, continuing to be detected up to 3-4 months after treatment.

It is not metabolized.

It is excreted unchanged in bile and urine: the main part of the drug is excreted within 24 hours, 11-14% is excreted by the kidneys within 48 hours.

Indications

Photodynamic therapy of malignant neoplasms: as an alternative method of treatment – for skin cancer, cancer of the lower lip, tumors of the oral mucosa (including tongue cancer), for stomach cancer (only in case of contraindications to surgical treatment); as a palliative method of treatment – stenosing cancer of the esophagus and stomach (for recanalization); intradermal metastases of breast cancer, melanoma.

Fluorescent diagnosis for detecting tumor boundaries, hidden tumors, determining the degree of drug accumulation in the tumor and surrounding tissues, monitoring the drug concentration in the skin, and assessing the duration of the period of skin phototoxicity.

ICD codes

Dosage Regimen

Intravenous drip, over 30 minutes, in a semi-darkened room, in a single dose of 0.8 mg/kg 24 hours before laser irradiation of the tumor.

The solution is preliminarily diluted with sterile 0.9% NaCl solution in a concentration of 1:4.

For the treatment of intradermal tumors, a dose reduction to 0.5 mg/kg is possible. In this case, the first PDT session is performed 1-24 hours after drug administration and the number of sessions is increased to 10.

Fluorescent diagnosis on any type of equipment that provides fluorescence excitation at a wavelength of 633 nm and spectral analysis, average laser radiation power – 2 mW, energy density of local laser irradiation on the surface of tissues during one examination – 1 J/sq.cm, which is significantly lower than the level of induction of irreversible photodynamic tissue damage, undesirable in diagnostic studies.

The average fluorescence value in the tumor and surrounding tissue after drug administration is determined 24 hours after administration. Before the 2nd, 3rd, and subsequent irradiation sessions during and after PDT, the fluorescence intensity of hydroxyaluminium trisulfophthalocyanine in the tumor and surrounding tissue is determined.

To correct the light regimen of patients, the fluorescence intensity in the skin is also determined after the completion of PDT. PDT is performed using light sources having a maximum emission at a wavelength of 675±5 nm and a half-wave of no more than 30 nm. Light sources must be normalized for the output power value and homogeneous distribution of power density over the irradiated surface.

To determine the energy density dose, the average power density over the spot is used, normalized to 1.2. The light exposure time is determined by the formula: light exposure time (sec) = required energy density (J/sq.cm) / power density (W/sq.cm).

The average power density during PDT should be within 100-300 mW/sq.cm, the energy density of one irradiation session – 100-300 J/sq.cm depending on the location and size of the tumor. The output power of the source is controlled by the built-in dosimeter or external meters before, during, and after each irradiation session. Control of the power density distribution over the irradiated surface is performed after each laser or light guide adjustment and after changing the waveguide.

Laser irradiation is performed using a flexible single-fiber light guide. Depending on the location and size of the tumor, 3 methods of laser irradiation of the affected area are used: 1) surface irradiation; 2) intratumoral irradiation with the introduction of a specially designed diffuser into the tissue; 3) mixed irradiation, i.e., a combination of surface and interstitial irradiation, performed sequentially or simultaneously (when treating widespread, predominantly exophytic tumors).

To protect the healthy skin surrounding the tumor and the patient’s eyes during irradiation, special protective screens made of dense dark paper are used.

When treating tumors of the skin and lower lip, analgesics and sedative medications are used as premedication. The first irradiation session begins 24 hours after drug administration. The number of sessions is 1-10 with an interval of 24-48 hours.

Adverse Reactions

Increased photosensitivity, skin hyperpigmentation, sunburns.

Local reactions: burning sensation, sharp pain at the irradiation site.

Contraindications

Hypersensitivity; renal failure; hepatic failure; pregnancy; lactation period.

Use in Pregnancy and Lactation

Contraindication: pregnancy and lactation period.

Use in Hepatic Impairment

Contraindication: hepatic failure.

Use in Renal Impairment

Contraindication: renal failure.

Special Precautions

Administration of the photosensitizer should be carried out under the supervision of a physician with subsequent clinical monitoring of the patient’s condition.

For 4-6 weeks after the administration of hydroxyaluminium trisulfophthalocyanine, the patient must be isolated from bright sunlight. The patient is allowed to stay in a room with artificial light sources.

With a sufficiently high radiation power density (200-300 mW/cm), the pain syndrome in the impact zone can persist from several hours to 1 day after PDT; relief of pain sensations in this case can only be achieved by using narcotic analgesics.

For the prevention and relief of toxic manifestations associated with skin photosensitivity, starting from the first days after PDT, strict adherence to the light regimen for 4-6 weeks, intake of antihistamine and antioxidant medications, and the use of sunscreens on exposed areas of the skin of the face and hands are recommended.

Drug Interactions

Does not cause toxic phenomena when combined with cisplatin, platidiam, fluorouracil, and epirubicin.

Ascorbic acid enhances the effect of PDT.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.