Visudyne

Dosage Forms And Strengths

VISUDYNE (verteporfin for injection) is a reconstituted sterile solution intended for intravenous injection only. Each reconstituted vial provides 7.5mL solution containing 2mg/mL of verteporfin.

Storage And Handling

VISUDYNE (verteporfin for injection) is supplied in a single-use glass vial with a gray bromobutyl stopper and aluminum flip-off cap. It contains a lyophilized dark green cake with 15 mg verteporfin.

NDC 0078-0437-61

Store VISUDYNE between 20°C and 25°C (68°F-77°F).

Spills and Disposal

Spills of VISUDYNE should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light. Use of rubber gloves and eye protection is recommended. All materials should be disposed of properly.

Accidental Exposure

Because of the potential to induce photosensitivity reactions, it is important to avoid contact with the eyes and skin during preparation and administration of VISUDYNE. Any exposed person must be protected from bright light.

Manufactured by: JHP Pharmaceuticals LLC Rochester, MI 48307 Or Hollister-Stier Laboratories Spokane, WA 99207. Revised Apr 2016

VISUDYNE (verteporfin for injection) therapy is indicated for the treatment of patients with predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis.

There is insufficient evidence to indicate VISUDYNE for the treatment of predominantly occult subfoveal choroidal neovascularization.

A course of VISUDYNE (verteporfin for injection) therapy is a two-step process requiring administration of both drug and light.

The first step is the intravenous infusion of VISUDYNE. The second step is the activation of VISUDYNE with light from a nonthermal diode laser.

The physician should re-evaluate the patient 3 months after treatment and if choroidal neovascular leakage is detected on fluorescein angiography, therapy may be repeated.

Lesion Size Determination

The greatest linear dimension (GLD) of the lesion should be estimated by fluorescein angiography and color fundus photography. All classic and occult CNV, blood and/or blocked fluorescence, and any serous detachments of the retinal pigment epithelium should be included for this measurement. Fundus cameras with magnification within the range of 2.4-2.6X are recommended. The GLD of the lesion on the fluorescein angiogram must be corrected for the magnification of the fundus camera to obtain the GLD of the lesion on the retina.

Spot Size Determination

The treatment spot size should be 1000 microns larger than the GLD of the lesion on the retina to allow a 500 micron border, ensuring full coverage of the lesion. The maximum spot size used in the clinical trials was 6400 microns.

The nasal edge of the treatment spot must be positioned at least 200 microns from the temporal edge of the optic disc, even if this will result in lack of photoactivation of CNV within 200 microns of the optic nerve.

VISUDYNE Administration

Reconstitute each vial of VISUDYNE with 7 mL of Sterile Water for Injection to provide 7.5 mL containing 2 mg/mL. Reconstituted VISUDYNE must be protected from light and used within 4 hours. It is recommended that reconstituted VISUDYNE be inspected visually for particulate matter and discoloration prior to administration. Reconstituted VISUDYNE is an opaque dark green solution. VISUDYNE may precipitate in saline solutions. Do not use normal saline or other parenteral solutions, except 5% Dextrose for Injection, for dilution of the reconstituted VISUDYNE. Do not mix VISUDYNE in the same solution with other drugs.

The volume of reconstituted VISUDYNE required to achieve the desired dose of 6 mg/m² body surface area is withdrawn from the vial and diluted with 5% Dextrose for Injection to a total infusion volume of 30 mL. After dilution, protect from light and use within 4 hours. The full infusion volume is administered intravenously over 10 minutes at a rate of 3 mL/minute, using an appropriate syringe pump and in-line filter. The clinical studies were conducted using a standard infusion line filter of 1.2 microns.

Precautions should be taken to prevent extravasation at the injection site. If extravasation occurs, protect the site from light.

Light Administration

Initiate 689 nm wavelength laser light delivery to the patient 15 minutes after the start of the 10-minute infusion with VISUDYNE.

Photoactivation of VISUDYNE is controlled by the total light dose delivered. In the treatment of choroidal neovascularization, the recommended light dose is 50 J/cm² of neovascular lesion administered at an intensity of 600 mW/cm². This dose is administered over 83 seconds.

Light dose, light intensity, ophthalmic lens magnification factor and zoom lens setting are important parameters for the appropriate delivery of light to the predetermined treatment spot. Follow the laser system manuals for procedure set up and operations.

The laser system must deliver a stable power output at a wavelength of 689±3 nm. Light is delivered to the retina as a single circular spot via a fiber optic and a slit lamp, using a suitable ophthalmic magnification lens.

The following laser systems have been tested for compatibility with VISUDYNE and are approved for delivery of a stable power output at a wavelength of 689±3 nm:

• Coherent Opal Photoactivator laser console and modified Coherent LaserLink adapter, manufactured by Lumenis, Inc., 2400 Condensa Street, Santa Clara, CA 95051-0901,
• Zeiss VISULAS 690s laser and VISULINK^® PDT adapter manufactured by Carl Zeiss Meditec Inc., 5160 Hacienda Drive, Dublin, CA 94568,
• Ceralas I laser system and Ceralink Slit Lamp Adapter manufactured by Biolitec Inc., 515 Shaker Road, East Longmeadow, MA 01028,
• Quantel Activis laser console and the ZSL30 ACT™, ZSL120 ACT™ and HSBMBQ ACT™ slit lamp adapters distributed by Quantel Medical, 601 Haggerty Lane, Bozeman, MT 59715

Concurrent Bilateral Treatment

The controlled trials only allowed treatment of one eye per patient. In patients who present with eligible lesions in both eyes, physicians should evaluate the potential benefits and risks of treating both eyes concurrently. If the patient has already received previous VISUDYNE therapy in one eye with an acceptable safety profile, both eyes can be treated concurrently after a single administration of VISUDYNE. The more aggressive lesion should be treated first, at 15 minutes after the start of infusion. Immediately at the end of light application to the first eye, the laser settings should be adjusted to introduce the treatment parameters for the second eye, with the same light dose and intensity as for the first eye, starting no later than 20 minutes from the start of infusion.

In patients who present for the first time with eligible lesions in both eyes without prior VISUDYNE therapy, it is prudent to treat only one eye (the most aggressive lesion) at the first course. One week after the first course, if no significant safety issues are identified, the second eye can be treated using the same treatment regimen after a second VISUDYNE infusion. Approximately 3 months later, both eyes can be evaluated and concurrent treatment following a new VISUDYNE infusion can be started if both lesions still show evidence of leakage.

Following intravenous infusion, verteporfin exhibits a bi-exponential elimination with a terminal elimination half-life of approximately 5-6 hours. The extent of exposure and the maximal plasma concentration are proportional to the dose between 6 and 20 mg/m². At the intended dose, pharmacokinetic parameters are not significantly affected by gender.

Verteporfin is metabolized to a small extent to its diacid metabolite by liver and plasma esterases. NADPH-dependent liver enzyme systems (including the cytochrome P450 isozymes) do not appear to play a role in the metabolism of verteporfin. Elimination is by the fecal route, with less than 0.01% of the dose recovered in urine.

In a study of patients with mild hepatic insufficiency (defined as having two abnormal hepatic function tests at enrollment), AUC and C_max were not significantly different from the control group, half-life however was significantly increased by approximately 20%.