Verteporfin For Injection

FDA Drug Information • Also known as: Visudyne

Brand Names: Visudyne
Drug Class: Photoenhancer [EPC]
Route: INTRAVENOUS
Dosage Form: INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION VISUDYNE ® (verteporfin for injection) is a sterile, photoenhancer which is light activated drug when used in photodynamic therapy for intravenous administration. The finished drug product is a lyophilized dark green cake. Verteporfin is a 1:1 mixture of two regioisomers (I and II), represented by the following structures: The chemical names for the verteporfin regioisomers are: 9-methyl (I) and 13-methyl (II) trans-(±)-18-ethenyl-4,4a,-dihydro-3,4-bis(methoxycarbonyl)-4a,8,14,19-tetramethyl-23H, 25H-benzo[b]porphine-9,13-dipropanoate The molecular formula is C 41 H 42 N 4 O 8 with a molecular weight of approximately 718.8. Each mL of reconstituted VISUDYNE contains: ACTIVE: verteporfin, 2 mg INACTIVES: ascorbyl palmitate (0.02 mg), butylated hydroxytoluene (0.002 mg), dimyristoyl phosphatidylcholine (9.4 mg), egg phosphatidylglycerol (6.5 mg), and lactose (92.0 mg). chem

What Is Verteporfin For Injection Used For?

1 INDICATIONS AND USAGE VISUDYNE ® (verteporfin for injection) therapy is indicated for the treatment of patients with predominantly classic subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), pathologic myopia or presumed ocular histoplasmosis. There is insufficient evidence to indicate VISUDYNE for the treatment of predominantly occult subfoveal CNV. VISUDYNE (verteporfin for injection) therapy is a photoenhancer indicated for the treatment of patients with predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION

Recommended Dose : 6 mg/m 2 body surface area. ( 2.2 )

Reconstitution : Reconstitute each vial of VISUDYNE with 7 mL of Sterile Water for Injection to provide 7.5 mL containing 2 mg/mL of verteporfin. Reconstituted VISUDYNE must be protected from light and used within 4 hours. ( 2.3 )

Dilution : Dilute desired dose of reconstituted VISUDYNE with 5% Dextrose for Injection to a total infusion volume of 30 mL. ( 2.3 )

Infusion : Administer intravenously over 10 minutes at a rate of 3 mL/minute, using an appropriate syringe pump and in-line filter. ( 2.3 )

Light Administration : The recommended light dose is 50 J/cm 2 of neovascular lesion administered at an intensity of 600 mW/cm 2 . The wavelength of the laser light should be 689±3 nm. This light dose is administered over 83 seconds, starting 15 minutes after the start of the VISUDYNE infusion. ( 2.4 ) 2.1 Important Administration Instructions 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 administration 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 1,000 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 6,400 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. 2.2 Recommended Dosage of VISUDYNE The recommended dose of VISUDYNE is 6 mg/m 2 body surface area. 2.3 VISUDYNE Administration Avoid contact with the eyes and skin during preparation and administration of VISUDYNE. Because of the potential to induce photosensitivity reactions, any exposed person must be protected from bright light [see Warnings and Precautions ( 5.1 ) and How Supplied/Storage and Handling ( 16 )] . Reconstitution Reconstitute each vial of VISUDYNE with 7 mL of Sterile Water for Injection. Each reconstituted vial provides 7.5 mL solution containing 2 mg/mL of...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling:

Local Adverse Reactions – Extravasation [see Warnings and Precautions ( 5.1 )]

Exposure to Sun or Direct Light [see Warnings and Precautions ( 5.2 )]

Decreased Vision after Treatment [see Warnings and Precautions ( 5.3 )]

Porphyria and Hypersensitivity [see Contraindications ( 4 )] Most common adverse reactions (incidence ˃10%) are injection site reactions and visual disturbances. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb Incorporated at 1-800-553-5340 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Severe chest pain, vasovagal and hypersensitivity reactions have been reported. Vasovagal and hypersensitivity reactions on rare occasions can be severe. These reactions may include syncope, sweating, dizziness, rash, dyspnea, flushing and changes in blood pressure and heart rate. General symptoms can include headache, malaise, urticaria, and pruritus. The most frequently reported adverse reactions to VISUDYNE (verteporfin for injection) are injection site reactions (including pain, edema, inflammation, extravasation, rashes, hemorrhage and discoloration) and visual disturbances (including blurred vision, flashes of light, decreased visual acuity and visual field defects, including scotoma). These events occurred in approximately 10%-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%-10% of patients: Ocular Treatment Site: Blepharitis, cataracts, conjunctivitis/conjunctival injection, dry eyes, ocular itching, severe vision decrease with or without subretinal/retinal or vitreous hemorrhage Body as a Whole: Asthenia, fever, flu syndrome, infusion related pain primarily presenting as back pain, 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, equivalent of >4 lines, within 7 days after treatment has been reported in 1%-5% of patients. Partial recovery of vision was observed in some patients. Photosensitivity reactions usually occurred in the form of skin sunburn following exposure to sunlight. The higher incidence of back pain in the VISUDYNE group occurred primarily during infusion. 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 reactions 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, retinal pigment epithelial tear. Non-ocular Events: Chest pain and other musculoskeletal pain during infusion, anaphylactic reaction during or following infusion, injection site necrosis.

Drug Interactions

7 DRUG INTERACTIONS Drug interaction studies in humans have not been conducted with VISUDYNE. Verteporfin is rapidly eliminated by the liver, mainly as unchanged drug. Metabolism is limited and occurs by liver and plasma esterases. Microsomal cytochrome P450 does not appear to play a role in verteporfin metabolism. Based on the mechanism of action of verteporfin, many drugs used concomitantly could influence the effect of VISUDYNE therapy. Possible examples include the following: Calcium channel blockers, polymyxin B or radiation therapy could enhance the rate of VISUDYNE uptake by the vascular endothelium. Other photosensitizing agents (e.g., tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics and griseofulvin) could increase the potential for skin photosensitivity reactions. Compounds that quench active oxygen species or scavenge radicals, such as dimethyl sulfoxide, β-carotene, ethanol, formate and mannitol, would be expected to decrease VISUDYNE activity. Drugs that decrease clotting, vasoconstriction or platelet aggregation, e.g., thromboxane A 2 inhibitors, could also decrease the efficacy of VISUDYNE therapy.

Contraindications

4 CONTRAINDICATIONS VISUDYNE (verteporfin for injection) is contraindicated for patients with porphyria or a known hypersensitivity to any component of this preparation [see Adverse Reactions ( 6 )] . VISUDYNE (verteporfin for injection) is contraindicated for patients with porphyria or a known hypersensitivity to any component of this preparation. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no data with the use of VISUDYNE in pregnant women to inform a drug-associated risk. Intravenous administration of verteporfin to pregnant rats during the period of organogenesis produced an increase in the incidence of anophthalmia/microphthalmia and wavy ribs at exposures approximately 40-fold the human exposure at the recommended clinical dose. Verteporfin did not produce adverse fetal effect in rats or rabbits at exposures 6- to 20-fold the human exposure at the recommended clinical dose. There are no adequate and well-controlled studies in pregnant women. VISUDYNE should be used during pregnancy only if the benefit justifies the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data Rat fetuses of dams administered verteporfin for injection intravenously during organogenesis exhibited an increase in the incidence of anophthalmia/microphthalmia and wavy ribs at doses ≥10 mg/kg/day (approximately 40-fold the human exposure at the recommended dose of 6 mg/m 2 , based on AUC in female rats). No teratogenic effects were observed in rat fetuses at a dose of 2 mg/kg/day (approximately 6-fold the human exposure at the recommended dose of 6 mg/m 2 , based on AUC in female rats). In pregnant rabbits, a decrease in maternal body weight gain and food consumption was observed in animals that received verteporfin for injection intravenously at doses up to 10 mg/kg/day during organogenesis. The no observed adverse effect level (NOAEL) for maternal toxicity was 3 mg/kg/day (approximately 6-fold the recommended human dose of 6 mg/m 2 , based on body surface area). No teratogenic effects were observed in rabbit fetuses at doses up to 10 mg/kg/day (approximately 20-fold the recommended human dose of 6 mg/m 2 , based on body surface area).

Overdosage

10 OVERDOSAGE Overdose of drug and/or light in the treated eye may result in non-perfusion of normal retinal vessels with the possibility of severe decrease in vision that could be permanent. An overdose of drug will also result in the prolongation of the period during which the patient remains photosensitive to bright light. In such cases, it is recommended to extend the photosensitivity precautions for a time proportional to the overdose.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING VISUDYNE ® (verteporfin for injection) is supplied in a single-dose glass vial with a gray bromobutyl stopper and aluminum flip-off cap. It contains a lyophilized dark green cake with 15 mg verteporfin. NDC 24208-560-15 Store VISUDYNE at controlled room temperature between 20°C to 25°C (68°F to 77°F). Protect from light. 16.1 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. 16.2 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 [see Warnings and Precautions ( 5.1 )] .

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.