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DOSAGE AND ADMINISTRATION
A course of Visudyne 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 non-thermal diode laser.
The physician should re-evaluate the patient every 3 months and if choroidal neovascular leakage is detected on fluorescein angiography, therapy should be administered.
Materials
Visudyne is supplied in single-use 15 mg vials as a sterile, lipid-based, freeze-dried cake that requires reconstitution with sterile Water for Injection and dilution with 5% Dextrose for Injection before administration. The product is intended for intravenous infusion only.
Storage
Visudyne supplies should be stored at room temperature between 20°C and 25°C (68°F-77°F).
Reconstitution
Before being injected, Visudyne must be reconstituted with 7 mL of sterile Water for Injection to provide 7.5 mL of reconstituted drug containing 2 mg/mL. Reconstituted Visudyne must be protected from light and used within 4 hours. It is recommended that the reconstituted drug be inspected visually for particulate matter and discoloration prior to administration. Reconstituted Visudyne is an opaque dark green solution.
Dilution
Reconstituted Visudyne must be further diluted with 5% Dextrose for Injection in order to achieve the desired drug dose of 6 mg/m² body surface area (BSA) and a total infusion volume of 30 mL. BSA can be determined using a nomogram or a graphic algorithm. After dilution, protect from light and use within a maximum of 4 hours.
Infusion
Administration
Visudyne solution is administered intravenously at a rate of 3 mL/min over 10 minutes, using an appropriate syringe pump and in-line filter. Clinical studies involving Visudyne have been conducted using a standard infusion line filter of 1.2 microns. To prevent extravasation, physicians should avoid fragile hand veins in favor of large antecubital veins. If extravasation occurs, the site must be protected from light (see Precautions).
Once infusion is complete, eyedrops are used to numb the eye. Approximately 15 minutes after infusion and no later than 5 minutes after eyedrop application, a special ophthalmic lens is placed over the eye.
Next, a cold laser light, spot-sized to match the appropriate part of the eye to be treated, is shone through this lens onto the eye, activating Visudyne. This step takes about 1½ minutes.
Activation
Determination of spot size and location
The spot size is determined by measuring the greatest linear dimension (GLD) of the entire lesion, including all classic and occult CNV, blood and/or blocked fluorescence, and any serous detachment of the RPE. This measurement can be estimated using a transparent millimeter ruler placed on a fluorescein angiogram obtained with a fundus camera. The GLD is divided by the camera lens magnification to determine the actual diameter of the lesion on the fundus in microns (µm). An additional 1000 µm is added to this value to allow a 500 µm margin to ensure full coverage of the lesion and to allow for small eye movements.
Irradiation of the optic disc
The light spot covering the lesion must come no closer than 200 µm to the temporal edge of the optic disc even if the lesion is located closer to it. If the lesion or proposed treatment area extends closer than 200 µm to the optic disc, it is considered appropriate to leave this portion of the lesion untreated.
Application of light
Red light (689 nm) at an intensity of 600 mW/cm² is delivered by a non-thermal diode laser 15 minutes after the start of the 10-minute Visudyne infusion. The light dose of 50 J/cm2 is delivered to the lesion from the diode laser as a circular spot via a fiber optic and slit lamp using a suitable ophthalmic magnification lens. The time to deliver the 50 J/cm² is 83 seconds.
Additional treatment
Patients should return for a follow-up examination approximately every 3 months after any initial or subsequent treatments. Patients are re-treated if there is evidence of leakage from any classic or occult CNV on the fluorescein angiogram and if they have not experienced any serious events likely to be associated with prior therapy.
Post-treatment
Patients who receive Visudyne will become temporarily photosensitive after the infusion. Patients should wear a wristband to remind them and others that they need to avoid bright light and direct sunlight for 5 days. During that period, patients should avoid exposure of unprotected skin, eyes or other body organs to direct sunlight or bright indoor light. Sources of bright light include, but are not limited to, tanning salons, bright halogen lighting and high power lighting used in surgical operating rooms or dental offices. Prolonged exposure to light from light-emitting medical devices such as pulse oximeters should also be avoided for 5 days following Visudyne administration.
If treated patients must go outdoors in daylight during the first 5 days after treatment, they should protect all parts of their skin and their eyes by wearing protective clothing and dark sunglasses. UV sunscreens are not effective in protecting against photosensitivity reactions because photoactivation of the residual drug in the skin can be caused by visible light. If emergency surgery is necessary within 48 hours after treatment, as much of the internal tissue as possible should be protected from intense light.
However, patients should not stay in the dark and should be encouraged to expose their skin to ambient indoor light, as it will help inactivate the drug in the skin through a process called photobleaching.
Concurrent bilateral treatment
Controlled trials involving Visudyne 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.
PRECAUTIONS
General
Standard precautions should be taken during infusion of Visudyne to avoid extravasation. Examples of standard precautions include, but are not limited to:
- A free-flowing intravenous (IV) line should be established before starting Visudyne infusion and the line should be carefully monitored
- Due to the possible fragility of vein walls of some elderly patients, it is strongly recommended that the largest arm vein possible, preferably antecubital, be used for injection
- Small veins in the back of the hand should be avoided. If extravasation does occur, the infusion should be stopped immediately and cold compresses applied (see Warnings)
Visudyne therapy should be considered carefully in patients with moderate to severe hepatic impairment or biliary obstruction since there is no clinical experience with verteporfin in such patients.
There are no clinical data related to the use of Visudyne in anesthetized patients. At a >10-fold higher dose given by bolus injection to sedated or anesthetized pigs, verteporfin caused severe hemodynamic effects, including death, probably as a result of complement activation. These effects were diminished or abolished by pretreatment with antihistamine
and they were not seen in conscious nonsedated pigs. Visudyne resulted in a concentration-dependent increase in complement activation in human blood in vitro. At 10 µg/mL (approximately 5 times the expected plasma concentration in human patients), there was mild to moderate complement activation. At ≥ 100 µg/mL, there was significant
complement activation. Signs (chest pain, syncope, dyspnea, and flushing) consistent with complement activation have been observed in <1% of patients administered Visudyne. Patients should be supervised during Visudyne infusion.
WARNINGS
Following injection with Visudyne, care should be taken to avoid exposure of skin or eyes to direct sunlight or bright indoor light for 5 days. In the event of extravasation during infusion, the extravasation area must be thoroughly protected from direct light until the swelling and discoloration have faded in order to prevent the occurrence of a local burn, which could be severe. If emergency surgery is necessary within 48 hours after treatment, as much of the internal tissue as possible should be protected from intense light.
Patients who experience severe vision loss of 4 lines or more within 1 week of treatment should not receive further treatment until their vision has returned to pretreatment levels. The potential benefits and risks of subsequent treatment must be carefully considered by the treating physician.
Use of incompatible lasers that do not provide the required characteristics of light for the photoactivation of Visudyne could result in incomplete treatment due to partial photoactivation of Visudyne, overtreatment due to overactivation of Visudyne, or damage to surrounding normal tissue.
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