Visudyne2 mg/ml

Visudyne is a light-activated (photosensitizing) medicine used in photodynamic therapy (PDT) of the eye. It is administered by intravenous infusion and then activated with a specific non-thermal laser light directed at the retina by an ophthalmologist.

FDA-approved / established indications

• Neovascular (wet) age-related macular degeneration (AMD) with predominantly classic subfoveal choroidal neovascularization (CNV).
• Subfoveal choroidal neovascularization due to pathologic myopia.
• Subfoveal choroidal neovascularization due to presumed ocular histoplasmosis syndrome (POHS).

Off-label use

Visudyne PDT is also used off-label by some ophthalmologists for chronic central serous chorioretinopathy (CSCR) and certain other choroidal vascular disorders; this use is not FDA-approved and should only be undertaken by a retina specialist after discussing the evidence and alternatives.

Each vial contains Verteporfin 15 mg as a sterile, lyophilized dark green cake/powder (benzoporphyrin derivative monoacid), for reconstitution with Sterile Water for Injection to give a concentration of 2 mg/mL prior to intravenous infusion.

Visudyne is a benzoporphyrin-derivative photosensitizing agent used exclusively in ophthalmic photodynamic therapy (PDT). After intravenous infusion, Visudyne circulates in the blood and accumulates preferentially in the abnormal, leaky blood vessels of choroidal neovascularization. When the treated area of the retina is then exposed to a specific low-intensity (non-thermal) laser light, the drug is activated and generates reactive oxygen species that selectively damage and occlude the abnormal vessels while relatively sparing surrounding normal retinal tissue.

Visudyne therapy must be administered in a hospital or specialist eye-care setting by a physician trained in the technique, using the specific laser equipment required for activation. It is not a self-administered or oral medicine.

Ophthalmic photosensitizing agent used for photodynamic therapy (PDT); benzoporphyrin derivative.

Verteporfin is a photosensitizer that, once activated by light of a specific wavelength, transfers energy to molecular oxygen to generate highly reactive singlet oxygen and other reactive oxygen species. Because Verteporfin is taken up preferentially by the proliferating endothelial cells of choroidal neovascularization (partly via low-density lipoprotein receptors, which are upregulated in these abnormal vessels), light activation causes localized endothelial damage, platelet activation, and thrombosis, leading to occlusion of the abnormal vasculature.

Pharmacokinetics: Verteporfin is extensively bound to plasma lipoproteins after intravenous infusion, distributes into tissue, and is eliminated primarily via biliary/faecal excretion as unchanged drug and its diacid metabolite, with a plasma elimination half-life of approximately 5–6 hours. Systemic skin photosensitivity therefore persists for a limited period (generally up to about 48 hours) after treatment.

Visudyne is reconstituted and diluted, then infused intravenously over 10 minutes through an in-line filter using an infusion pump, avoiding extravasation. Laser light activation of the treated retinal lesion is performed exactly 15 minutes after the start of the infusion begins, by the treating ophthalmologist. The infusion line and any exposed skin should be protected from bright light during and after administration. See Dosage and Administration for full timing and light-dose details.

Formal drug-interaction studies with Visudyne are limited, but the following interactions are clinically recognized:

• Other photosensitizing agents (e.g. tetracyclines, sulfonamides, phenothiazines, sulfonylureas, thiazide diuretics, griseofulvin): concurrent use may increase the risk and severity of photosensitivity reactions.
• Radical/singlet-oxygen scavengers (e.g. high-dose vitamin C, vitamin E, beta-carotene, mannitol, ethanol, formate): may theoretically reduce the effectiveness of Visudyne photodynamic therapy by interfering with the reactive-oxygen mechanism.
• Vasoconstrictors, calcium-channel blockers and polymyxin B: have been reported in preclinical/clinical data to alter vascular uptake or the effect of Visudyne PDT; use with caution around the time of treatment.
• Prior or concurrent ocular radiation therapy or other retinal treatments: may increase local tissue effects; discuss timing with the treating ophthalmologist.

Tell the treating physician about all medicines, supplements, and recent light-based or radiation treatments before Visudyne therapy.

Most adverse effects of Visudyne therapy are related to the infusion, the injection site, or the eye itself.

• Very common/common: visual disturbances (blurred vision, decreased vision, flashing lights), injection-site reactions (pain, swelling, inflammation), infusion-related back pain, headache, and general weakness (asthenia).
• Photosensitivity reactions of skin and eyes if exposed to direct sunlight or bright light within about 48 hours of treatment (see Precautions and Warnings).
• Severe or acute decrease in vision has been reported within days of treatment in a small proportion of patients; patients should be monitored and instructed to report any sudden vision change immediately.
• Extravasation at the infusion site can cause severe local pain, inflammation, and a photosensitivity-type skin reaction/burn if the extravasation site is subsequently exposed to light.
• Less common: nausea, fever, allergic-type reactions (rash, urticaria), and changes in liver enzymes.

There are no adequate and well-controlled studies of Visudyne in pregnant women, and choroidal neovascularization requiring this treatment is uncommon in pregnancy. Visudyne should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; a physician should be consulted before use. It is not known whether Visudyne or its metabolites pass into human breast milk; caution is advised, and a physician should be consulted to weigh the benefits of treatment against the possible risks to a nursing infant.

Photosensitivity reaction: After Visudyne infusion, patients are temporarily photosensitive. Direct sunlight and bright indoor light (e.g. examination lamps, tanning beds, halogen lighting) on unprotected skin and eyes must be avoided for approximately 48 hours after treatment. Protective clothing, sunglasses, and wide-brimmed hats should be worn if going outdoors is unavoidable during this period; ordinary sunscreen does not protect against this reaction because it works on a different wavelength range.

Extravasation: Care is required during intravenous administration, as leakage of Visudyne outside the vein can cause severe local pain and, if the area is subsequently exposed to light, a serious burn-like photosensitivity reaction. The infusion site should be monitored throughout administration.

Acute severe vision loss: A small proportion of patients have experienced a marked decrease in vision within days of Visudyne treatment. Patients should be examined promptly if vision worsens after treatment.

Specialist administration only: Visudyne must be given only by, or under the direct supervision of, a physician trained in ophthalmic photodynamic therapy, with the specific laser equipment required for activation. It should not be given if the required laser follow-up cannot be arranged.

Porphyria: see Contraindications.

Overdose of Visudyne (drug and/or excessive light exposure) may prolong and intensify photosensitivity reactions and increase the risk of damage to normal retinal/choroidal tissue. There is no specific antidote. If overdose is suspected, seek immediate medical attention or contact a poison control center; the patient should be protected from direct sunlight and bright light for an extended period (longer than the usual 48 hours) as advised by the treating physician, and supportive care should be provided as needed.

Store unopened Visudyne vials at 20°C to 25°C (68°F to 77°F), protected from light, in the original carton. After reconstitution, protect the solution from light and use within 4 hours; do not freeze. Keep out of reach of children.

Elderly: Age-related macular degeneration primarily affects older adults, who form the main population treated with Visudyne; no specific dose adjustment is needed beyond calculating dose by body surface area.

Renal impairment: Data are limited; use with caution.

Hepatic impairment: Data are limited, and biliary excretion is a major elimination route for Visudyne; use with caution in moderate-to-severe hepatic impairment or biliary obstruction, as systemic photosensitivity may be prolonged.

Pregnancy and lactation: see Pregnancy and Lactation.

Pediatric use: see Pediatric Uses.

Visudyne photodynamic therapy is not given on a fixed course; each treatment session (infusion plus laser activation) is followed by re-evaluation, typically with fluorescein angiography around 3 months later. Retreatment with Visudyne is repeated only if leakage or active choroidal neovascularization persists or recurs, for as long as the treating ophthalmologist judges it clinically beneficial.

Each vial of Visudyne (15 mg) is reconstituted with 7 mL of Sterile Water for Injection to yield 7.5 mL of solution containing 2 mg/mL. The reconstituted solution is dark green and should be visually inspected; do not use if particulate matter or discoloration is present. The required dose (based on 6 mg/m² body surface area) is then withdrawn and further diluted with 5% Dextrose Injection to a total infusion volume of 30 mL. The diluted solution must be protected from light and used within 4 hours of reconstitution. Do not mix with saline solutions or other diluents.

Photosensitizing agent; photodynamic therapy (PDT) agent; benzoporphyrin derivative; ophthalmic (retinal) therapeutic agent.

Verteporfin accumulates preferentially in the abnormal neovascular endothelium of choroidal neovascularization. When activated by non-thermal laser light of a matched wavelength (689 nm), it generates reactive oxygen species (including singlet oxygen) that damage the endothelium, trigger platelet aggregation, and cause localized thrombotic occlusion of the abnormal blood vessels, while sparing adjacent normal retinal tissue relatively better than non-selective destructive techniques.

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The safety and effectiveness of Visudyne in children have not been established. Choroidal neovascularization requiring photodynamic therapy is rare in the pediatric population; use in children should only be considered by a pediatric retina specialist when no suitable alternative exists and the potential benefit is judged to outweigh the risks.