Verteporfin

VISUDYNE ® (verteporfin for injection) therapy is indicated for the treatment of patients with predominantly classic subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), pathologic myopia or presumed ocular histoplasmosis. There is insufficient evidence to indicate VISUDYNE for the treatment of predominantly occult subfoveal CNV. VISUDYNE (verteporfin for injection) therapy is a photoenhancer indicated for the treatment of patients with predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis.

VISUDYNE (verteporfin for injection) therapy is a two-stage process requiring administration of both verteporfin for injection and nonthermal red light. Verteporfin is transported in the plasma primarily by lipoproteins. Once verteporfin is activated by light in the presence of oxygen, highly reactive, short-lived singlet oxygen and reactive oxygen radicals are generated. Light activation of verteporfin results in local damage to neovascular endothelium, resulting in vessel occlusion. Damaged endothelium is known to release procoagulant and vasoactive factors through the lipoxygenase (leukotriene) and cyclooxygenase (eicosanoids such as thromboxane) pathways, resulting in platelet aggregation, fibrin clot formation and vasoconstriction. Verteporfin appears to somewhat preferentially accumulate in neovasculature, including choroidal neovasculature.

Recommended Dose: 6 mg/m 2 body surface area. Reconstitution: Reconstitute each vial of VISUDYNE with 7 mL of Sterile Water for Injection to provide 7.5 mL containing 2 mg/mL of verteporfin. Reconstituted VISUDYNE must be protected from light and used within 4 hours. Dilution: Dilute desired dose of reconstituted VISUDYNE with 5% Dextrose for Injection to a total infusion volume of 30 mL. Infusion: Administer intravenously over 10 minutes at a rate of 3 mL/minute, using an appropriate syringe pump and in-line filter. Light Administration: The recommended light dose is 50 J/cm 2 of neovascular lesion administered at an intensity of 600 mW/cm 2. The wavelength of the laser light should be 689±3 nm. This light dose is administered over 83 seconds, starting 15 minutes after the start of the VISUDYNE infusion.

VISUDYNE (verteporfin for injection) is contraindicated for patients with porphyria or a known hypersensitivity to any component of this preparation.

Extravasation: If extravasation occurs, the infusion should be stopped immediately. The extravasation area must be thoroughly protected from direct light until swelling and discoloration have faded in order to prevent the occurrence of local burn. Exposure to Sun or Direct Light: Following injection with VISUDYNE (verteporfin for injection), care should be taken to avoid exposure of skin or eyes to direct sunlight or bright indoor light for 5 days. Anaphylactic Reactions: Immediately discontinue administration of VISUDYNE and initiate appropriate therapy if an anaphylactic or other serious allergic reaction occurs during or following infusion.

The following serious adverse reactions are described elsewhere in the labeling: Local Adverse Reactions – Extravasation Exposure to Sun or Direct Light Decreased Vision after Treatment Porphyria and Hypersensitivity Most common adverse reactions (incidence ˃10%) are injection site reactions and visual disturbances.

Drug interaction studies in humans have not been conducted with VISUDYNE. Verteporfin is rapidly eliminated by the liver, mainly as unchanged drug. Metabolism is limited and occurs by liver and plasma esterases. Microsomal cytochrome P450 does not appear to play a role in verteporfin metabolism. Based on the mechanism of action of verteporfin, many drugs used concomitantly could influence the effect of VISUDYNE therapy. Possible examples include the following: Calcium channel blockers, polymyxin B or radiation therapy could enhance the rate of VISUDYNE uptake by the vascular endothelium. Other photosensitizing agents (e.g., tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics and griseofulvin) could increase the potential for skin photosensitivity reactions.

Store VISUDYNE between 20°C to 25°C (68°F to 77°F). Any exposed person must be protected from bright light.