Visudyne

Visudyne is part of a group of antineoplastic drugs that are used to perform photodynamic treatment procedures.

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

Indications Visudyne

It is used for the following diseases:

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

Release form

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

Pharmacodynamics

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

The selectivity of photodynamic treatment using verteporfin is based, in addition to the local effect of light, on the accelerated absorption and selective retention of verteporfin by rapidly proliferating cells (including the endothelium of the choroidal neovascularization region). [ 3 ]

Pharmacokinetics

Distribution processes.

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

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

Exchange processes.

The ester subgroup of verteporfin is hydrolyzed by liver and plasma esterases to form the 2-basic benzoporphyrin derivative (BPD-DA). This element is also a photosensitizer, but its overall effect is weaker (5-10% of verteporfin exposure indicates that the drug is largely excreted unchanged).

Excretion.

Verteporfin is excreted biexponentially after infusion. The exposure level and plasma Cmax values correspond to a dosage of 6-20 mg/m2.

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

The combined urinary excretion of verteporfin and BPD-DA is less than 1%, suggesting that they are excreted via bile.

Dosing and administration

The therapy is carried out in 2 stages.

During the first, a 10-minute infusion of Visudin is performed in a portion of 6 mg/m2 of 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 fluid (it is necessary to make 7.5 ml of the solution, the concentration of which is 2 mg/ml). To administer a dosage of 6 mg/m2, it is necessary to dissolve the required amount of the obtained liquid in 5% injection glucose (dextrose) with a final volume of 30 ml. Saline solutions cannot be used. Standard droppers with hydrophilic walls (pore size - at least 1.2 μm) should be used.

In the 2nd 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 689 nm + 3 nm). It is directed to the area of the neovascular choroidal lesion through an optical fiber 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 during the same period with an error of +/- 2 weeks.

• Application for children

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

Use Visudyne during pregnancy

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

Verteporfin with its 2-main metabolite is found in human breast milk. When a single dose of 6 mg/m2 was administered, the verteporfin level in breast milk was 66% of the corresponding plasma level and was not detected after 12 hours. The 2-main metabolite had lower Cmax values, which persisted for approximately 48 hours. Due to the lack of information on the effect of these components on infants, it is necessary to stop breastfeeding or postpone therapy (taking into account the risks of delay for the woman). Taking into account the decrease in the 2-main metabolite levels during the 48-hour period, breastfeeding should not be done for 96 hours after using the drug.

Contraindications

Contraindicated for use in cases of severe intolerance to verteporfin or other components of the drug, as well as in cases of porphyria.

Side effects Visudyne

Main side effects:

• Visual disturbances: visual disturbances are common and include flashes of light, fog, visual field defects (dark/gray halos), blurriness, decreased vision, blurred vision, black spots, and scotomas. Retinal detachment, vitreous hemorrhage, or retinal/subretinal hemorrhage are sometimes seen;
• injection site abnormalities: swelling, transudation, pain and inflammation are common. Sometimes intolerance symptoms, discoloration and hemorrhage occur;
• General adverse events: infusion-related pain (mainly back pain), asthenia, and photosensitivity symptoms (sunburn, usually occurring within 24 hours of infusion) were common. Nausea, hypertension, fever, and hypoesthesia were occasionally observed. Blistering at the injection site or choroidal or retinal vascular occlusion were rare;
• Systemic disorders: vasovagal symptoms and signs of intolerance (sometimes severe). Systemic manifestations include malaise, dizziness, fainting, headache, sweating, dyspnea, urticaria, rashes, itching and flushing of the face, as well as changes in blood pressure or heart rate.
• Pain in the chest and back caused by the infusion may spread to other areas (sternum or shoulder and pelvic girdle).

Overdose

Poisoning from drugs or light used in therapy can cause selective blockage of healthy retinal blood vessels, which can severely impair vision.

An overdose of the drug may prolong the period of increased photosensitivity in the patient for several days. In such cases, patients, taking into account the degree of poisoning, need to prolong the period of avoiding exposure of the eyes and skin to bright artificial light and direct sunlight.

Interactions with other drugs

The use of other photosensitizing agents (eg, phenothiazines, tetracycline, antidiabetic drugs, sulfonamides, griseofulvin, sulfonylureas, and thiazide diuretics) may increase the likelihood of developing photosensitivity symptoms.

Storage conditions

Visudin should be stored in a place out of reach of small children. Temperature values should not exceed 25oС.

Shelf life

Visudin can be used for a period of 4 years from the date of sale of the therapeutic agent. The shelf life of the reconstituted and diluted liquid is 4 hours.

Analogues

Analogues of the drug are Oxsoralen, Ammifurin, Lamadin with Beroxan and Alasens.