Visudyne (Verteporfin)

Visudyne 15 mg powder for solution for infusion

Verteporfin

Age-related macular degeneration (AMD) is the leading cause of blindness among people over the age of 50 in the western world. It is characterized by two forms: the “dry” form, as well as the more severe “wet” form. While the wet form of AMD – which afflicts about 500,000 people each year – is responsible for only about 15% of all AMD cases, it accounts for some 90% of the severe vision loss associated with AMD. Wet AMD typically destroys central vision in as little as two months to three years; central vision is necessary for reading, driving, and recognizing faces.

The most common form of age-related macular degeneration treatment has been laser photocoagulation, which helps prevent the progression of choroidal neovascularization (CNV) in the 10-20% of AMD patients who have small, discrete lesions. However, the thermal lasers used in this technique also destroy healthy retinal tissue, resulting in an immediate loss of visual acuity after treatment.

WHAT VISUDYNE IS AND WHAT IT IS USED FOR

What Visudyne is

Visudyne contains the active substance verteporfin, which is activated by light from a laser in a treatment called photodynamic therapy. When you are given an infusion of Visudyne, it is distributed within your body through the blood vessels, including the blood vessels at the back of the eye. When the laser light is shone into the eye, Visudyne is activated.

Brand Name Drug: Visudyne
Active Ingredient Drug: verteporfin for injection
Company Name: CIBA Vision, the eye care unit of Novartis Pharmaceuticals Corporation
Availability: Approvable letter issued by FDA on February 11, 2000

What Visudyne is used for

Visudyne is used to treat the wet form of age-related macular degeneration and pathological myopia.

These diseases lead to vision loss. Vision loss is caused by new blood vessels (choroidal neovascularisation) that damage the retina (the light-sensitive membrane that lines the back of the eye). There are two types of choroidal neovascularisation: classic and occult.

Visudyne is used for the treatment of predominantly classic choroidal neovascularisation in adults with age-related macular degeneration, and also for the treatment of all types of choroidal neovascularisation in adults with pathological myopia.

Visudyne: Clinical Study Results

A one-year analysis from two 24-month randomized double-masked clinical trials involving 609 patients with a variety of CNV lesion characteristics, known as the TAP (Treatment of AMD with Photodynamic therapy) Investigation, showed that vision remained stable or improved (defined as a loss of less than 3 lines of vision on a standard eye chart) for 61% of patients treated with Visudyne therapy compared to 46% of patients administered placebo – a significant difference. Patients in these studies had a late form of wet AMD.

Compared to placebo, the beneficial effects of Visudyne therapy with respect to change in visual acuity were observed three months after initial treatment and became more pronounced through month 12. The entire change in visual acuity distribution at 12 months differed by an average of 1.3 lines in favor of those patients on Visudyne. Although the goal of Visudyne therapy is to reduce the risk of vision loss, 16% of patients in the treatment group experienced an improvement in vision of one or more lines on a standard eye chart, compared to 7% of patients on placebo. Severe vision loss (defined as a loss of at least 6 lines of vision on a standard eye chart) occurred in 14.7% of patients treated with Visudyne therapy as opposed to 23.7% of patients on placebo.

Positive visual acuity results were complemented by similar outcomes for contrast sensitivity evaluations. In addition, fluorescein angiographic assessments demonstrated that Visudyne significantly reduced the risk of lesion growth, was associated with the cessation of leakage from classic CNV, and decreased progression in the development of new areas of classic choroidal neovascularization beyond that observed at study entry.

No subgroups were identified in which placebo-treated patients fared significantly better than patients receiving Visudyne therapy. However, the visual acuity benefit observed in the overall population was substantially enhanced in 243 patients whose lesions at baseline constituted predominantly classic CNV. Vision remained stable or improved in 67% of these patients treated with Visudyne therapy versus 39% on placebo. At 12 months, 12% of these patients on Visudyne therapy had lost greater than six lines of vision, whereas 33.3% of placebo patients in this subgroup had experienced severe vision loss.

Repeat treatments were administered every three months if leakage was identified on fluorescein angiography. At the 12-month time period, only 64% of the Visudyne-treated patients required repeat treatment.

Additional clinical trials are being conducted to assess the efficacy of Visudyne for patients with an earlier stage of age-related macular degeneration, pathologic myopia, and ocular histoplasmosis.

BEFORE YOU ARE GIVEN VISUDYNE

You should not be given Visudyne

• if you are allergic (hypersensitive) to verteporfin or any of the other ingredients of Visudyne.
• if you have porphyria (a rare condition that may increase sensitivity to light).
• if you have any severe liver problems.

If any of these apply to you, tell your doctor. You should not be given Visudyne.

Take special care with Visudyne

If you experience any problems or symptoms during the treatment such as chest pain, sudden loss of consciousness, sweating, dizziness, rash, breathlessness, flushing, irregular heart beat, please tell your doctor or nurse.

If you have any liver problems or a blockage of your bile duct, please tell your doctor before starting Visudyne therapy.

If, during the infusion, Visudyne goes outside the vein, and especially if the affected area is exposed to light, this can cause pain, swelling, blistering and a change in skin colour in the area of the leakage. If this happens, the infusion needs to be stopped and the skin treated with cold compresses and thoroughly protected from light until the skin colour returns to normal. You may need to take a painkiller.

You will be sensitive to bright light for 48 hours after the infusion. During that time, avoid exposure to direct sunlight, bright indoor lights such as in tanning salons, bright halogen lighting, high power lighting as used by surgeons or dentists, or light from light-emitting medical devices such as pulse oximeters (used to measure oxygen in blood). If you have to go outdoors during daylight in the first 48 hours after treatment, you must protect your skin and eyes by wearing protective clothing and dark sunglasses. Sunscreens offer no protection.

Normal indoor lighting is safe.

Do not stay in the dark because exposure to normal indoor lighting will help your body to eliminate Visudyne more quickly.

If you experience any eye problems after the treatment, such as a vision loss, talk to your doctor.

Using other medicines

Please tell your doctor, nurse or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

If you are taking any of the following medicines:

• tetracyclines or sulphonamides (used to treat bacterial infection),
• phenothiazines (used to treat psychiatric disorders, or nausea and vomiting),
• sulfonylurea (used to treat diabetes),
• medicines used to lower blood sugar,
• thiazide diuretics (used to reduce high blood pressure),
• griseofulvin (used to treat fungal infection) tell your doctor or pharmacist. This is important because taking these medicines may increase your sensitivity to light.

Pregnancy and breastfeeding

Visudyne has not been studied in pregnant women. It is important to tell your doctor if you are pregnant, if you think you may be pregnant or if you plan to become pregnant. You should only be given Visudyne if your doctor considers it absolutely essential. Verteporfin is excreted in human milk in low amounts. Please tell your doctor if you are breastfeeding. He/she will decide whether you should be given Visudyne. It is recommended that, if you are given Visudyne, you do not breastfeed for 48 hours after administration.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

After Visudyne treatment you may have some vision problems, such as abnormal or decreased vision, which may be temporary. If this happens to you, do not drive or use any tools or machines until your vision improves.

Important information about some of the ingredients of Visudyne

Visudyne contains small amounts of butylated hydroxytoluene (E321). This ingredient is irritant to eyes, skin and mucous membranes.

If you come into direct contact with Visudyne, you must therefore wash it off extensively with water.

HOW VISUDYNE IS USED

Treatment with Visudyne is a two-step process

• First your doctor or the pharmacist will prepare the Visudyne infusion solution. It will be administered by your doctor or nurse into a vein using a drip (intravenous infusion).
• The second step is the activation of Visudyne in the eye 15 minutes after the start of the infusion. Your doctor will put a special contact lens onto your eye and treat your eye using a special laser. It takes 83 seconds to deliver the laser dose required to activate Visudyne. During this time, you will have to follow your doctor’s instructions and keep your eyes still.

If necessary, Visudyne therapy can be repeated every 3 months, up to 4 times per year.

Use in children

Visudyne is a treatment for adults only and not indicated for the use in children.

If you are given more Visudyne than you should be

Overdose of Visudyne may prolong the time during which you are sensitive to light and you may need to follow the protection instructions given in section 2 for longer than 48 hours. Your doctor will advise you.

Overdose of Visudyne and light in the treated eye may result in severe vision decrease.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

POSSIBLE SIDE EFFECTS

Like all medicines, Visudyne can cause side effects, although not everybody gets them. These side effects may occur with certain frequencies, which are defined as follows:

Very common	affects more than 1 user in 10
Common	affects 1 to 10 users in 100
Uncommon	affects 1 to 10 users in 1,000
Rare	affects 1 to 10 users in 10,000
Very rare	affects less than 1 user in 10,000
Not known	frequency cannot be estimated from the available data.

Most of the side effects are mild to moderate and will usually disappear a few days to a few weeks after treatment.

Common side effects

• Eye disorders: severe decrease of vision (loss of 4 lines or more within 7 days of treatment), visual disturbances such as blurred, hazy or fuzzy vision, flashes of light, decreased vision, and a change in the field of vision in the treated eye such as grey or dark shadows, blind spots or black spots.
• Infusion site side effects: as with other types of injections, some patients experienced pain, swelling, inflammation, and weeping from the infusion site.
• General disorders: feeling sick (nausea), sunburn-like reactions, tiredness, infusion-related reaction, primarily presented as back pain which may radiate to other areas, including but not limited to, the pelvis, shoulders or rib cage, and increased cholesterol.

Uncommon side effects

• Eye disorders: bleeding of the retina or into the vitreous humour (the clear gel-like substance that fills the eyeball behind the lens), and displacement of the retina in the treated eye.
• Infusion site side effects: as with other types of injections, some patients experienced bleeding at the infusion site, change in skin colour and hypersensitivity. If this happens to you, there will be increased sensitivity to light in that part of the skin until the green discolouration disappears.
• General disorders: pain, increased blood pressure, increased sensation, and fever.

Rare frequency side effects

• Eye disorders: lack of blood circulation to the retina or choroids (the vascular layer of the eye) in the treated eye.

Not known frequency side effects

• Eye disorders: tear in the coloured layer of the retina.
• Infusion site side effects: as with other types of injections, some patients experienced blistering.
• General disorders: vasovagal reactions (light-headedness and fainting) and allergic reactions, which on rare occasions can be severe, have been reported. General symptoms can include headache, malaise (feeling unwell), fainting, sweating, dizziness, rash, hives, itching, breathlessness, flushing, or changes in blood pressure and heart rate. Infusion-related reaction, primarily presented as chest pain which may radiate to other areas, including but not limited to, the pelvis, shoulders or rib cage.
• Heart attack has been reported, particularly in patients with a history of heart disease, sometimes within 48 hours after treatment with Visudyne. In the event of suspected heart attack, seek medical attention immediately.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or nurse.

HOW TO STORE VISUDYNE

Keep out of the reach and sight of children.

Do not use Visudyne after the expiry date which is stated on the carton and vial after ‘EXP’. The expiry date refers to the last day of that month.

Do not store above 25°C. Keep the vial in the outer carton in order to protect from light.

Chemical and physical in-use stability has been demonstrated for 4 hours at 25 °C. From a microbiological point of view, the medicine should be used immediately. If not used immediately, the in-use storage time and conditions prior to use are the responsibility of the user and would normally not last longer than 4 hours below 25 °C protected from light.

FURTHER INFORMATION

What Visudyne contains

The active substance is verteporfin. Each vial contains 15 mg of verteporfin. After reconstitution, 1 ml contains 2 mg of verteporfin. 7.5 ml of reconstituted solution contains 15 mg of verteporfin.

The other ingredients are dimyristoyl phosphatidylcholine, egg phosphatidylglycerol, ascorbyl palmitate, butylated hydroxytoluene (E321) and lactose monohydrate.

What Visudyne looks like and contents of the pack

Visudyne is supplied as a dark green to black powder in a clear glass vial. The powder is reconstituted in water prior to use to form an opaque dark green solution.

Visudyne is available in packs containing 1 vial of powder.