Vizudin

Vizudin belongs to a group of antineoplastic drugs that are used to perform photodynamic treatment procedures.

The active element of the drug verteporfin is a so-called derivative of benzoporphyrin monoacid (BPD-MA), which includes a combination of BPD-MAD regioisomers with BPD-MAC, which have the same activity (these components are contained in it in a 1 to 1 ratio). The medication is used as a light-activating substance (it is a photosensitizer). [1]

Indications Vizudin

It is used for such diseases:

• neovascularization of the choroidal subfoveal type (mainly classical or latent), caused by macular degeneration caused by age-related changes;
• neovascularization of the subfoveal choroidal nature associated with ocular histoplasmosis , pathological myopia, or other lesions in the macular region.

Release form

The release of a therapeutic substance is realized in the form of an infusion lyophilisate - inside 15 mg vials (inside a pack - 1 vial).

Pharmacodynamics

Verteporfin produces cytotoxins exclusively in the presence of oxygen, activated by light. After absorption by porphyrin, energy is converted into oxygen, after which a short singlet oxygen is formed, which has a powerful reactivity. It destroys biological structures in the diffusion area, which causes local vascular occlusion and cell damage. In addition, under certain conditions, cell death can occur. [2]

The selectivity of photodynamic treatment with verteporfin is based, in addition to the local influence of light, on the accelerated absorption and selective retention of verteporfin produced by rapidly proliferating cells (among them the endothelium of the choroidal area of neovascularization). [3]

Pharmacokinetics

Distribution processes.

The Cmax after a 10-minute infusion for 6 and 12 mg / m2 body surface area is approximately 1.5 and 3.5 μg / ml.

Intraplasmic synthesis of the substance occurs with lipoprotein fractions (90%) and albumin (about 6%).

Exchange processes.

The ester subgroup of verteporfin is involved in hydrolysis by liver and plasma esterases, resulting in the formation of a 2-main benzoporphyrin derivative (BPD-DA). This element is also a photosensitizer, but its overall effect is weaker (5-10% of the effect of verteporfin shows that the drug is mainly excreted unchanged).

Excretion.

The excretion of verteporfin after infusion is biexponential. The exposure level and the plasma Cmax correspond to a dosage of 6-20 mg / m2.

The term plasma half-life is approximately 5-6 hours. This figure was about 20% higher in people with mild liver failure.

The combined excretion of verteporfin and BPD-DA together with urine is less than 1%, which suggests that they are excreted in the bile.

Dosing and administration

The therapy is performed in 2 stages.

During the first, a 10-minute infusion of Vizudin is performed in a portion of 6 mg / m2 of the body surface (it is necessary to dilute the portion in 30 ml of solution).

The solution is prepared as follows: the medicine is diluted in 7 ml of injection liquid (it is necessary to make 7.5 ml of the solution, the concentration of which is 2 mg / ml). To enter a dosage of 6 mg / m2, you need to dissolve the required amount of the resulting liquid in 5% injectable glucose (dextrose) with a final volume of 30 ml. Saline solutions cannot be used. A standard type of dropper with hydrophilic walls (pore size minimum 1.2 μm) should be used.

At the second stage, the drug is activated by light (after 15 minutes from the start of the infusion). The procedure is performed using a diode laser that emits red, non-thermal light (with a wavelength of 689nm + 3nm). It is directed into the area of neovascular choroidal injury through an optical fiberglass device mounted on a slit lamp (using an appropriate contact lens). In the case of using the recommended light intensity of 600 mW / cm, the transmission of the required portion of light of 50 J / cm is equal to 83 seconds.

Patients should be examined every 3 months. Treatment is performed in the same period with an error of +/- 2 weeks.

• Application for children

The use of the drug in pediatrics has not been studied.

Use Vizudin during pregnancy

The use of Vizudine during pregnancy has not been studied, therefore, it can be prescribed only in situations where the likelihood of benefit outweighs the possible risks of complications in the fetus.

Verteporfin, with its 2-major metabolic element, is found inside human breast milk. With the introduction of a single portion of 6 mg / m2, the verteporfin index inside breast milk was 66% of the corresponding plasma level and did not appear after 12 hours. The 2-main metabolite had lower Cmax values, which persisted up to about 48 hours. Due to the lack of information regarding the effect of these components on infants, it is necessary to abandon hepatitis B or postpone therapy (taking into account the risks of delay for the woman). Taking into account the decrease in the indicators of the 2-main metabolite in the period of 48 hours, breastfeeding should not be performed within 96 hours after using the drug.

Contraindications

It is contraindicated to prescribe with severe intolerance to verteporfin or other elements of drugs, as well as porphyria.

Side effects Vizudin

The main side signs:

• visual disorders: visual disturbances often occur, including flashes of light, nebula, visual field defects (the appearance of a dark / gray halo), blurring, blurred vision and blurred vision, black spots and scotomas. Sometimes there is retinal detachment, vitreous hemorrhage, or retinal / subretinal hemorrhage;
• violations in the area of the injection: swelling, transudation, pain and inflammation are often noted. Sometimes symptoms of intolerance, discoloration and hemorrhage appear;
• general negative manifestations: pain associated with infusion (mainly dorsal), asthenia and signs of photosensitivity (sunburn, usually occurring within 24 hours after infusion) often occurred. Nausea, hypertension, fever, and hypesthesia are sometimes noted. Occasionally, there was the formation of blisters in the area of the injection or blockage of the choroidal or retinal vessels;
• systemic disorders: vasovagus symptoms and signs of intolerance (sometimes severe). Systemic manifestations include malaise, dizziness, fainting, cephalalgia, sweating, dyspnoea, urticaria, rashes, itching and flushing of the skin of the face, as well as changes in blood pressure or heart rate.
• Infusion-induced chest and back pain can spread to other areas (sternum or shoulder and pelvic girdle).

Overdose

Poisoning with drugs or light used in therapy can selectively block healthy retinal vessels, which can severely impair vision.

An overdose of medication can increase the period of increased photosensitivity in a patient by several days. In such cases, patients, taking into account the degree of poisoning, need to extend the term for avoiding exposure to the eyes and skin of bright artificial light and direct sunlight.

Interactions with other drugs

When using other photosensitizing substances (for example, phenothiazines, tetracycline, antidiabetic drugs, sulfonamides, griseofulvin, sulfonylureas and thiazide diuretics), the likelihood of photosensitivity symptoms may increase.

Storage conditions

Vizudin should be kept out of the reach of small children. Temperature values - no more than 25oС.

Shelf life

Vizudine can be used for a 4-year term from the date of sale of the therapeutic agent. The shelf life of the reconstituted and diluted liquid is 4 hours.

Analogs

The analogues of the medication are the drugs Oxoralen, Ammifurin, Lamadin with Beroxan and Alasens.