Visudyne

IV Preparation

Reconstitute 15 mg drug with 7 mL SWI to obtain a 2 mg/mL opaque dark-green solution

Protect from light & use within 4 hr

Further dilute in D5W to match 6 mg/sq.meter dose and infusion volume of 30 mL

After dilution protect from light & use within 4 hr

IV Administration

Infuse the 30 mL solution at rate of 3 mL/min over 10 min

Large antecubital veins are preferred to avoid extravasation

Extravasation Management

Stop infusion immediately & apply cold compresses

Protect extravasation site from light

Serious side effects have been reported with Visudyne including the following:

• decrease or changes in vision
• seeing flashes of light
• black spots in vision
• redness and swelling of the eyelid
• pink eye
• chest pain
• fainting
• sweating
• rash
• shortness of breath
• flushing
• rapid or irregular heartbeat
• headache
• lack of energy
• hives and itching

Visudyne can cause blurred vision and dizziness. Do not drive or operate heavy machinery until you know how Visudyne affects you.

Do not take Visudyne if you:

• are allergic to Visudyne or to any of its ingredients
• have porphyria (a condition that causes sensitivity to light)

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Visudyne, there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Visudyne has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from Visudyne, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.

Verteporfin is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. Verteporfin must be given slowly, and the IV infusion can take at least 10 minutes to complete.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when verteporfin is injected.

You will receive laser light treatment to your eye(s) within 15 minutes after the start of your verteporfin infusion.

After receiving verteporfin, you must protect your eyes from natural sunlight and bright indoor light for at least 5 days.. For best protection, wear dark sunglasses whenever you are outdoors or while indoors under bright lighting.

You should not stay in the dark while you are indoors, as this can actually cause the drug to stay active in your body longer. It is best to spend your time in ambient indoor light such as indirect sunlight through a window, or low-wattage incandescent lighting. Avoid areas where you will be exposed to halogen or fluorescent light.

Your doctor will need to check your progress on a regular basis. Do not miss any scheduled appointments.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severely decreased vision.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; sweating; dizziness; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have:

• severe decrease in vision;

• sudden and severe pain;

• severe redness or other discoloration of your eyes;

• eye pain or seeing halos around lights;

• feeling like you might pass out;

• chest pain; or

• flushing (warmth, redness, or tingly feeling).

Common side effects may include:

• slight changes in your vision, seeing flashes of light;

• dry eyes;

• redness, swelling, or itching of your eyelids;

• headache, feeling weak or tired;

• mild itching or skin rash;

• constipation, nausea;

• joint pain, muscle weakness;

• fever, chills, flu symptoms; or

• pain, swelling, bleeding, or itching where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• It is used to treat macular degeneration.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.
• A laser is needed to make Visudyne work.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

Local Adverse Reactions – Extravasation

Standard precautions should be taken during infusion of Visudyne (verteporfin for injection) 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. Extravasation of Visudyne, especially if the affected area is exposed to light, can cause severe pain, inflammation, swelling or discoloration at the injection site.

If extravasation does occur, 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, which could be severe. Cold compresses should be applied to the injection site. Oral medications for pain relief may be administered.

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. 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.

Decreased Vision after Treatment

Patients who experience severe decrease of vision of 4 lines or more within 1 week after treatment should not be retreated, at least until their vision completely recovers to pretreatment levels and the potential benefits and risks of subsequent treatment are carefully considered by the treating physician.

Mechanism of Action

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 cyclo-oxygenase (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. However, animal models indicate that the drug is also present in the retina. Therefore, there may be collateral damage to retinal structures following photoactivation including the retinal pigmented epithelium and outer nuclear layer of the retina. The temporary occlusion of the choroidal neovascularization (CNV) following Visudyne therapy has been confirmed in humans by fluorescein angiography.

Pharmacokinetics

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 Cmax were not significantly different from the control group; half-life, however, was significantly increased by approximately 20%.

Applies to verteporfin: powder for solution

Along with its needed effects, verteporfin (the active ingredient contained in Visudyne) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking verteporfin:

• Blurred vision or other change in vision

• Decrease in vision, may be severe
• dizziness
• dull nervousness
• eye pain
• fainting
• fast, slow, or irregular heartbeat
• itching, redness, or other irritation of eye
• pale skin
• pounding in the ears
• troubled breathing on exertion
• unusual bleeding or bruising
• unusual tiredness or weakness

Some side effects of verteporfin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, infection, itching, numbness, pain, rash, redness, scarring, stinging, swelling, tenderness, tingling, ulceration, and/or warmth at the injection site
• headache

• Back pain (during infusion of verteporfin)
• chills
• cloudy urine
• constipation
• cough
• decreased hearing
• decreased sensitivity to touch
• diarrhea
• difficult or painful urination
• difficulty in moving
• double vision
• dry eyes
• feeling of constant movement of self or surroundings
• fever
• general feeling of discomfort or illness
• hoarseness
• increased sensitivity of skin to sunlight
• joint pain
• light headedness
• loss of appetite
• loss of strength or energy
• muscle pain or stiffness
• nausea
• pain, swelling, or redness in joints
• pelvic discomfort
• redness or other discoloration of skin
• runny nose
• severe sunburn
• shivering
• skin rash
• sore throat
• sweating
• tearing
• tender, swollen glands in neck
• throat congestion
• trouble in sleeping
• trouble in swallowing
• trouble sleeping
• varicose veins
• voice changes
• vomiting