Safety

Aided by more than 5 years of clinical experience, Visudyne has a well-established safety profile. The most frequently reported adverse events in treatment with Visudyne are injection site reactions (including extravasation and rashes), blurred vision, decreased visual acuity, and visual field defects. These events occurred in approximately 10% to 30% of patients.

The following events, listed by Body System, were reported more frequently with Visudyne therapy than with placebo therapy and occurred in 1% to 10% of patients:

Ocular treatment site:		Blepharitis, cataracts, conjunctivitis/conjunctival injection, dry eyes, ocular itching, severe vision loss with or without subretinal or vitreous hemorrhage
Body as a whole:		Asthenia, back pain (primarily during infusion), fever, flu syndrome, photosensitivity reactions
Cardiovascular:		Atrial fibrillation, hypertension, peripheral vascular disorder, varicose veins
Dermatologic:		Eczema
Digestive:		Constipation, gastrointestinal cancers, nausea
Hemic and lymphatic:		Anemia, white blood cell count decreased, white blood cell count increased
Hepatic:		Elevated liver function tests
Metabolic/nutritional:		Albuminuria, creatinine increased
Musculoskeletal:		Arthralgia, arthrosis, myasthenia
Nervous system:		Hypesthesia, sleep disorder, vertigo
Respiratory:		Cough, pharyngitis, pneumonia
Special senses:		Cataracts, decreased hearing, diplopia, lacrimation disorder
Urogenital:		Prostatic disorder

Severe vision decrease (≥4 lines on Snellen chart) was reported within 7 days in 1% to 5% of patients. Partial recovery occurs in some patients. Do not re-treat these patients until vision completely recovers to pretreatment levels and potential benefits and risks of subsequent treatment are carefully weighed.

Infusion-related transient back pain occurred with Visudyne only. Infusion induces temporary photosensitivity; patients should avoid exposure of skin and eyes to direct sunlight or bright indoor light for 5 days. To prevent extravasation, avoid fragile hand veins in favor of larger, antecubital veins.

The following adverse events have occurred either at low incidence (<1%) during clinical trials or have been reported during the use of Visudyne in clinical practice where these events were reported voluntarily from a population of unknown size and frequency of occurrence cannot be determined precisely. They have been chosen for inclusion based on factors such as seriousness, frequency of reporting, possible causal connection to Visudyne, or a combination of these factors:

Ocular treatment site:		Retinal detachment (nonrhegmatogenous), retinal or choroidal vessel nonperfusion
Nonocular events:		Chest pain and other musculoskeletal pain during infusion, hypersensitivity reactions (which can be severe), syncope, severe allergic reactions with dyspnea and flushing, and vaso-vagal reactions.

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.