HIGHLIGHTS OF PRESCRIBING INFORMATION Ceralas I laser system and Ceralink Slit Lamp Adapter manufactured by Biolitec Inc.

,
515 Shaker Road, East Longmeadow, MA 01028,
These highlights do not include all the information needed to use VISUDYNE safely and effectively. See full prescribing ---------------------------------------------------- CONTRAINDICATIONS-----------------------------------------------------
information for VISUDYNE. Quantel Activis laser console and the ZSL30 ACT, ZSL120 ACT and HSBMBQ ACT slit lamp adapters distributed by
VISUDYNE is contraindicated for patients with porphyria or a known hypersensitivity to any component of this preparation. (4) Quantel Medical, 601 Haggerty Lane, Bozeman, MT 59715
VISUDYNE® (verteporfin for injection), for intravenous use
Initial U.S. Approval: 2000 ----------------------------------------------- WARNINGS AND PRECAUTIONS------------------------------------------------ 2.5 Concurrent Bilateral Treatment
• Extravasation: If extravasation occurs, the infusion should be stopped immediately. The extravasation area must be The controlled trials only allowed treatment of one eye per patient. In patients who present with eligible lesions in both eyes,
-------------------------------------------------- INDICATIONS AND USAGE--------------------------------------------------- thoroughly protected from direct light until swelling and discoloration have faded in order to prevent the occurrence physicians should evaluate the potential benefits and risks of treating both eyes concurrently. If the patient has already received
VISUDYNE therapy is indicated for the treatment of patients with predominantly classic subfoveal choroidal neovascularization of local burn. (5.1) previous VISUDYNE therapy in one eye with an acceptable safety profile, both eyes can be treated concurrently after a single
due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis. (1) • Following injection with VISUDYNE, care should be taken to avoid exposure of skin or eyes to direct sunlight or bright administration of VISUDYNE. The more aggressive lesion should be treated first, at 15 minutes after the start of infusion.
indoor light for 5 days. (5.2) Immediately at the end of light application to the first eye, the laser settings should be adjusted to introduce the treatment
----------------------------------------------- DOSAGE AND ADMINISTRATION------------------------------------------------ parameters for the second eye, with the same light dose and intensity as for the first eye, starting no later than 20 minutes from
• Reconstitute each vial of VISUDYNE with 7 mL of Sterile Water for Injection to provide 7.5 mL containing 2 mg/mL. ---------------------------------------------------- ADVERSE REACTIONS----------------------------------------------------- the start of infusion.
Reconstituted VISUDYNE must be protected from light and used within 4 hours. (2.3) Most common adverse reactions (incidence >10%) are: In patients who present for the first time with eligible lesions in both eyes without prior VISUDYNE therapy, it is prudent to treat
• The recommended light dose is 50 J/cm2 of neovascular lesion administered at an intensity of 600 mW/cm2. The • injection site reactions (6.1) only one eye (the most aggressive lesion) at the first course. One week after the first course, if no significant safety issues are
wavelength of the laser light should be 689±3 nm. This light dose is administered over 83 seconds, starting 15 minutes • visual disturbances (6.1) identified, the second eye can be treated using the same treatment regimen after a second VISUDYNE infusion. Approximately
after the start of the VISUDYNE infusion. (2.4) 3 months later, both eyes can be evaluated and concurrent treatment following a new VISUDYNE infusion can be started if both
To report SUSPECTED ADVERSE REACTIONS, contact Bausch + Lomb, a division of Valeant Pharmaceuticals North lesions still show evidence of leakage.
----------------------------------------------DOSAGE FORMS AND STRENGTHS----------------------------------------------- America LLC, at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
3 DOSAGE FORMS AND STRENGTHS
• VISUDYNE is a reconstituted sterile solution intended for intravenous injection. (3) See 17 for PATIENT COUNSELING INFORMATION. VISUDYNE is a reconstituted sterile solution intended for intravenous injection only. Each reconstituted vial provides 7.5 mL
• Each reconstituted vial provides 7.5 mL solution containing 2 mg/mL of verteporfin. (3) solution containing 2 mg/mL of verteporfin.
Revised: 02/2017
4 CONTRAINDICATIONS
VISUDYNE is contraindicated for patients with porphyria or a known hypersensitivity to any component of this preparation [see
Adverse Reactions (6)].
FULL PRESCRIBING INFORMATION: CONTENTS* 5 WARNINGS AND PRECAUTIONS
1 INDICATIONS AND USAGE 8.4 Pediatric Use 5.1 Local Adverse Reactions - Extravasation
2 DOSAGE AND ADMINISTRATION 8.5 Geriatric Use Standard precautions should be taken during infusion of VISUDYNE to avoid extravasation. Examples of standard precautions
2.1 Lesion Size Determination 10 OVERDOSAGE include, but are not limited to:
2.2 Spot Size Determination 11 DESCRIPTION • A free-flowing intravenous (IV) line should be established before starting VISUDYNE infusion and the line should be
2.3 VISUDYNE Administration carefully monitored.
12 CLINICAL PHARMACOLOGY • Due to the possible fragility of vein walls of some elderly patients, it is strongly recommended that the largest arm vein
2.4 Light Administration
12.1 Mechanism of Action possible, preferably antecubital, be used for injection.
2.5 Concurrent Bilateral Treatment
12.3 Pharmacokinetics • Small veins in the back of the hand should be avoided.
3 DOSAGE FORMS AND STRENGTHS
13 NONCLINICAL TOXICOLOGY Extravasation of VISUDYNE, especially if the affected area is exposed to light, can cause severe pain, inflammation, swelling or
4 CONTRAINDICATIONS 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility discoloration at the injection site.
5 WARNINGS AND PRECAUTIONS 13.2 Animal Toxicology and/or Pharmacology If extravasation does occur, the infusion should be stopped immediately. The extravasation area must be thoroughly protected
5.1 Local Adverse Reactions - Extravasation from direct light until swelling and discoloration have faded in order to prevent the occurrence of local burn, which could be
14 CLINICAL STUDIES severe. Cold compresses should be applied to the injection site. Oral medications for pain relief may be administered.
5.2 Exposure to Sun or Direct Light 14.1 Age-Related Macular Degeneration (AMD)
5.3 Decreased Vision After Treatment 14.2 Pathologic Myopia 5.2 Exposure to Sun or Direct Light
14.3 Presumed Ocular Histoplasmosis Following injection with VISUDYNE, care should be taken to avoid exposure of skin or eyes to direct sunlight or bright indoor
Rev. 02/2017 9589700 6 ADVERSE REACTIONS light for 5 days. In the event of extravasation during infusion, the extravasation area must be thoroughly protected from direct
6.1 Clinical Trials Experience 16 HOW SUPPLIED/STORAGE AND HANDLING light until the swelling and discoloration have faded in order to prevent the occurrence of a local burn which could be severe. If
7 DRUG INTERACTIONS 16.1 Spills and Disposal emergency surgery is necessary within 48 hours after treatment, as much of the internal tissue as possible should be protected
(verteporfin for injection) 16.2 Accidental Exposure from intense light.
8 USE IN SPECIFIC POPULATIONS
Visudyne® 8.1 Pregnancy 17 PATIENT COUNSELING INFORMATION 5.3 Decreased Vision After Treatment
8.2 Lactation Patients who experience severe decrease of vision of 4 lines or more within 1 week after treatment should not be retreated, at
*Sections or subsections omitted from the full prescribing information are not listed. 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.

6 ADVERSE REACTIONS
FULL PRESCRIBING INFORMATION 2.3 VISUDYNE Administration
The following serious adverse reactions are described elsewhere in the labeling:
Reconstitute each vial of VISUDYNE with 7 mL of Sterile Water for Injection to provide 7.5 mL containing 2 mg/mL of verteporfin.
Visudyne® 1 INDICATIONS AND USAGE
VISUDYNE (verteporfin for injection) therapy is indicated for the treatment of patients with predominantly classic
Reconstituted VISUDYNE must be protected from light and used within 4 hours. It is recommended that reconstituted VISUDYNE
be inspected visually for particulate matter and discoloration prior to administration. Reconstituted VISUDYNE is an opaque dark
• Local Adverse Reactions – Extravasation [see Warnings and Precautions (5.1)]
• Exposure to Sun or Direct Light [see Warnings and Precautions (5.2)]
(verteporfin for injection) subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), pathologic myopia or
presumed ocular histoplasmosis.
green solution. VISUDYNE may precipitate in saline solutions. Do not use normal saline or other parenteral solutions, except 5%
Dextrose for Injection, for dilution of the reconstituted VISUDYNE. Do not mix VISUDYNE in the same solution with other drugs.
• Decreased Vision After Treatment [see Warnings and Precautions (5.3)]
• Porphyria and Hypersensitivity [see Contraindications (4)]
There is insufficient evidence to indicate VISUDYNE for the treatment of predominantly occult subfoveal CNV. The volume of reconstituted VISUDYNE required to achieve the desired dose of 6 mg/m2 body surface area is withdrawn from the
9589700 Rev. 02/2017 vial and diluted with 5% Dextrose for Injection to a total infusion volume of 30 mL. After dilution, protect from light and use within 6.1 Clinical Trials Experience
2 DOSAGE AND ADMINISTRATION 4 hours. The full infusion volume is administered intravenously over 10 minutes at a rate of 3 mL/minute, using an appropriate Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of
A course of VISUDYNE therapy is a two-step process requiring administration of both drug and light. syringe pump and in-line filter. The clinical studies were conducted using a standard infusion line filter of 1.2 microns. a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice.
The first step is the intravenous infusion of VISUDYNE. The second step is the activation of VISUDYNE with light from a nonthermal Precautions should be taken to prevent extravasation at the injection site. If extravasation occurs, protect the site from light [see Severe chest pain, vasovagal and hypersensitivity reactions have been reported. Vasovagal and hypersensitivity reactions on rare
diode laser. Warnings and Precautions (5.1)]. occasions can be severe. These reactions may include syncope, sweating, dizziness, rash, dyspnea, flushing and changes in blood
The physician should re-evaluate the patient 3 months after treatment and if choroidal neovascular leakage is detected on pressure and heart rate. General symptoms can include headache, malaise, urticaria, and pruritus.
2.4 Light Administration
fluorescein angiography, therapy may be repeated. The most frequently reported adverse reactions to VISUDYNE are injection site reactions (including pain, edema, inflammation,
Initiate 689 nm wavelength laser light delivery to the patient 15 minutes after the start of the 10 minute infusion with VISUDYNE. extravasation, rashes, hemorrhage and discoloration) and visual disturbances (including blurred vision, flashes of light, decreased
2.1 Lesion Size Determination Photoactivation of VISUDYNE is controlled by the total light dose delivered. In the treatment of CNV, the recommended light dose visual acuity and visual field defects, including scotoma). These events occurred in approximately 10%-30% of patients. The
The greatest linear dimension (GLD) of the lesion should be estimated by fluorescein angiography and color fundus photography. is 50 J/cm2 of neovascular lesion administered at an intensity of 600 mW/cm2. This dose is administered over 83 seconds. following events, listed by Body System, were reported more frequently with VISUDYNE therapy than with placebo therapy and
All classic and occult CNV, blood and/or blocked fluorescence, and any serous detachments of the retinal pigment epithelium Light dose, light intensity, ophthalmic lens magnification factor and zoom lens setting are important parameters for the appropriate occurred in 1%-10% of patients:
should be included for this measurement. Fundus cameras with magnification within the range of 2.4-2.6X are recommended. delivery of light to the predetermined treatment spot. Follow the laser system manuals for procedure set up and operations.
The GLD of the lesion on the fluorescein angiogram must be corrected for the magnification of the fundus camera to obtain the Ocular Treatment Site: Blepharitis, cataracts, conjunctivitis/conjunctival infection, dry eyes, ocular itching, severe vision
The laser system must deliver a stable power output at a wavelength of 689±3 nm. Light is delivered to the retina as a single decrease with or without subretinal/retinal or vitreous hemorrhage
GLD of the lesion on the retina. circular spot via a fiber optic and a slit lamp, using a suitable ophthalmic magnification lens.
Body as a Whole: Asthenia, fever, flu syndrome, infusion related pain primarily presenting as back pain,
2.2 Spot Size Determination The following laser systems have been tested for compatibility with VISUDYNE and are approved for delivery of a stable power photosensitivity reactions
The treatment spot size should be 1000 microns larger than the GLD of the lesion on the retina to allow a 500 micron border, output at a wavelength of 689±3 nm:
ensuring full coverage of the lesion. The maximum spot size used in the clinical trials was 6400 microns. Cardiovascular: Atrial fibrillation, hypertension, peripheral vascular disorder, varicose veins
Coherent Opal Photoactivator laser console and modified Coherent LaserLink adapter, manufactured by Lumenis, Inc.,
The nasal edge of the treatment spot must be positioned at least 200 microns from the temporal edge of the optic disc, even if 2400 Condensa Street, Santa Clara, CA 95051-0901, Dermatologic: Eczema
this will result in lack of photoactivation of CNV within 200 microns of the optic nerve. Zeiss VISULAS 690s laser and VISULINK PDT adapter manufactured by Carl Zeiss Meditec Inc., 5160 Hacienda Drive, Digestive: Constipation, gastrointestinal cancers, nausea
Dublin, CA 94568, Hemic and Lymphatic: Anemia, white blood cell count decreased, white blood cell count increased
Hepatic: Elevated liver function tests
Metabolic/Nutritional: Albuminuria, creatinine increased 11 DESCRIPTION The subgroup of patients with predominately classic CNV lesions was more likely to exhibit a treatment benefit (N=242;
Musculoskeletal: Arthralgia, arthrosis, myasthenia VISUDYNE is a light activated drug used in photodynamic therapy. The finished drug product is a lyophilized dark green cake. VISUDYNE 159, placebo 83).
Verteporfin is a 1:1 mixture of two regioisomers (I and II), represented by the following structures: Predominantly classic CNV lesions were defined as those in which the classic component comprised 50% or more of the area
Nervous System: Hypesthesia, sleep disorder, vertigo
of the entire lesion. For the primary efficacy endpoint (percentage of patients who lost less than 3 lines of visual acuity), these
Respiratory: Cough, pharyngitis, pneumonia patients showed a difference of approximately 28% between treatment groups at both Months 12 and 24 (67% for VISUDYNE
Special Senses: Cataracts, decreased hearing, diplopia, lacrimation disorder patients compared to 40% for placebo patients, at Month 12; and 59% for VISUDYNE patients compared to 31% for placebo
patients, at Month 24). Severe vision loss (≥6 lines of visual acuity from baseline) was experienced by 12% of VISUDYNE-treated
Urogenital: Prostatic disorder
patients compared to 34% of placebo-treated patients at Month 12, and by 15% of VISUDYNE-treated patients compared to
Severe vision decrease, equivalent of >4 lines, within 7 days after treatment has been reported in 1%-5% of patients. Partial 36% of placebo-treated patients at Month 24.
recovery of vision was observed in some patients. Photosensitivity reactions usually occurred in the form of skin sunburn following Patients with predominantly classic CNV lesions that did not contain occult CNV exhibited the greatest benefit (N=134; VISUDYNE
exposure to sunlight. The higher incidence of back pain in the VISUDYNE group occurred primarily during infusion. 90, placebo 44). At 1 year, these patients demonstrated a 49% difference between treatment groups when assessed by the
The following adverse events have occurred either at low incidence (<1%) during clinical trials or have been reported during <3 lines-lost definition (77% vs. 27%).
the use of VISUDYNE in clinical practice where these reactions were reported voluntarily from a population of unknown size Older patients (≥75 years), patients with dark irides, patients with occult lesions or patients with less than 50% classic CNV were
and frequency of occurrence cannot be determined precisely. They have been chosen for inclusion based on factors such as less likely to benefit from VISUDYNE therapy.
seriousness, frequency of reporting, possible causal connection to VISUDYNE, or a combination of these factors: The safety and efficacy of VISUDYNE beyond 2 years have not been demonstrated.
Ocular Treatment Site: Retinal detachment (nonrhegmatogenous), retinal or choroidal vessel nonperfusion, retinal Based on the Treatment of Age Related Macular Degeneration with Photodynamic Therapy Study (TAP) extension study, the
pigment epithelial tear. average number of treatments per year were 3.5 in the first year after diagnosis, 2.4 in the second, 1.3 in the third, 0.4 in the
Non-ocular Events: Chest pain and other musculoskeletal pain during infusion The chemical names for the verteporfin regioisomers are: fourth and 0.1 in the fifth year.
9-methyl (I) and 13-methyl (II) trans-(±)-18-ethenyl-4,4a,-dihydro-3,4-bis(methoxycarbonyl)-4a,8,14,19-tetramethyl-23H, 14.2 Pathologic Myopia
7 DRUG INTERACTIONS 25H-benzo[b]porphine-9,13-dipropanoate
One adequate and well-controlled, double-masked, placebo-controlled, randomized study was conducted in patients with
Drug interaction studies in humans have not been conducted with VISUDYNE.
The molecular formula is C41H42N4O8 with a molecular weight of approximately 718.8. Each mL of reconstituted VISUDYNE contains: subfoveal CNV secondary to pathologic myopia. A total of 120 patients (VISUDYNE 81, placebo 39) were enrolled in the study. The
Verteporfin is rapidly eliminated by the liver, mainly as unchanged drug. Metabolism is limited and occurs by liver and plasma treatment dosing and retreatments were the same as in the AMD studies. The difference between treatment groups statistically
esterases. Microsomal cytochrome P450 does not appear to play a role in verteporfin metabolism. ACTIVE: Verteporfin, 2 mg
favored VISUDYNE at the 1-year analysis but not at the 2-year analysis for visual acuity endpoints. For the primary efficacy
Based on the mechanism of action of verteporfin, many drugs used concomitantly could influence the effect of VISUDYNE therapy. INACTIVES: Ascorbyl palmitate, butylated hydroxytoluene, dimyristoyl phosphatidylcholine, endpoint (percentage of patients who lost less than 3 lines of visual acuity), patients at the 1-year timepoint showed a difference
Possible examples include the following: egg phosphatidylglycerol and lactose of approximately 19% between treatment groups (86% for VISUDYNE patients compared to 67% for placebo patients). However,
Calcium channel blockers, polymyxin B or radiation therapy could enhance the rate of VISUDYNE uptake by the vascular by the 2-year timepoint, the effect was no longer statistically significant (79% for VISUDYNE patients compared to 72% for
endothelium. Other photosensitizing agents (e.g., tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, 12 CLINICAL PHARMACOLOGY placebo patients).
thiazide diuretics and griseofulvin) could increase the potential for skin photosensitivity reactions. Compounds that quench 12.1 Mechanism of Action Based on the Verteporfin in Photodynamic Therapy in Pathologic Myopia (VIP-PM) extension study in pathologic myopia, the
active oxygen species or scavenge radicals, such as dimethyl sulfoxide, β-carotene, ethanol, formate and mannitol, would be VISUDYNE therapy is a two-stage process requiring administration of both verteporfin for injection and nonthermal red light. average number of treatments per year were 3.5 in the first year after diagnosis, 1.8 in the second, 0.4 in the third, 0.2 in the
expected to decrease VISUDYNE activity. Drugs that decrease clotting, vasoconstriction or platelet aggregation, e.g., thromboxane Verteporfin is transported in the plasma primarily by lipoproteins. Once verteporfin is activated by light in the presence of oxygen, fourth and 0.1 in the fifth.
A2 inhibitors, could also decrease the efficacy of VISUDYNE therapy. highly reactive, short-lived singlet oxygen and reactive oxygen radicals are generated. Light activation of verteporfin results in 14.3 Presumed Ocular Histoplasmosis
local damage to neovascular endothelium, resulting in vessel occlusion. Damaged endothelium is known to release procoagulant One open-label study was conducted in patients with subfoveal CNV secondary to presumed ocular histoplasmosis. A total of
8 USE IN SPECIFIC POPULATIONS
and vasoactive factors through the lipoxygenase (leukotriene) and cyclo-oxygenase (eicosanoids such as thromboxane) pathways, 26 patients were treated with VISUDYNE in the study. The treatment dosing and retreatments for VISUDYNE were the same as the
8.1 Pregnancy resulting in platelet aggregation, fibrin clot formation and vasoconstriction. Verteporfin appears to somewhat preferentially AMD studies. VISUDYNE-treated patients compare favorably with historical control data demonstrating a reduction in the number
accumulate in neovasculature, including choroidal neovasculature. However, animal models indicate that the drug is also present of episodes of severe visual acuity loss (>6 lines of loss).
Risk Summary
in the retina. Therefore, there may be collateral damage to retinal structures following photoactivation including the retinal
There are no data with the use of VISUDYNE in pregnant women to inform a drug-associated risk. Intravenous administration pigmented epithelium and outer nuclear layer of the retina. The temporary occlusion of the CNV following VISUDYNE therapy has Based on the Visudyne Ocular Histoplasmosis extension study in presumed ocular histoplasmosis, the average number of
of verteporfin to pregnant rats during the period of organogenesis produced an increase in the incidence of anophthalmia/ been confirmed in humans by fluorescein angiography. treatments per year was 2.9 in the first year after diagnosis, 1.2 in the second, 0.2 in the third and 0.1 in the fourth.
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 12.3 Pharmacokinetics 16 HOW SUPPLIED/STORAGE AND HANDLING
recommended clinical dose. Following intravenous infusion, verteporfin exhibits a bi-exponential elimination with a terminal elimination half-life of VISUDYNE (verteporfin for injection) is supplied in a single-use glass vial with a gray bromobutyl stopper and aluminum flip-off
There are no adequate and well-controlled studies in pregnant women. VISUDYNE should be used during pregnancy only if the approximately 5-6 hours. The extent of exposure and the maximal plasma concentration are proportional to the dose between cap. It contains a lyophilized dark green cake with 15 mg verteporfin.
benefit justifies the potential risk to the fetus. 6 and 20 mg/m2. At the intended dose, pharmacokinetic parameters are not significantly affected by gender. NDC 0187-5600-15
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized Verteporfin is metabolized to a small extent to its diacid metabolite by liver and plasma esterases. NADPH-dependent liver enzyme Store VISUDYNE between 20°-25°C (68°-77°F).
pregnancies is 2%-4% and 15%-20%, respectively. 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. 16.1 Spills and Disposal
Data In a study of patients with mild hepatic insufficiency (defined as having two abnormal hepatic function tests at enrollment), Spills of VISUDYNE should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for
Animal Data AUC and Cmax were not significantly different from the control group; half-life, however, was significantly increased by photosensitivity reactions upon exposure to light. Use of rubber gloves and eye protection is recommended. All materials should
Rat fetuses of dams administered verteporfin for injection intravenously during organogenesis exhibited an increase in the approximately 20%. be disposed of properly.
incidence of anophthalmia/microphthalmia and wavy ribs at doses ≥10 mg/kg/day (approximately 40-fold the human exposure at 16.2 Accidental Exposure
the recommended dose of 6 mg/m2, based on AUC in female rats). No teratogenic effects were observed in rat fetuses at a dose 13 NONCLINICAL TOXICOLOGY
Because of the potential to induce photosensitivity reactions, it is important to avoid contact with the eyes and skin during
of 2 mg/kg/day (approximately 6-fold the human exposure at the recommended dose of 6 mg/m2, based on AUC in female rats). 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility preparation and administration of VISUDYNE. Any exposed person must be protected from bright light [see Warnings and
In pregnant rabbits, a decrease in maternal body weight gain and food consumption was observed in animals that received Precautions (5.2)].
verteporfin for injection intravenously at doses up to 10 mg/kg/day during organogenesis. The no observed adverse effect level Carcinogenesis
(NOAEL) for maternal toxicity was 3 mg/kg/day (approximately 6-fold the recommended human dose of 6 mg/m2, based on body No studies have been conducted to determine the carcinogenic potential of verteporfin. 17 PATIENT COUNSELING INFORMATION
surface area). No teratogenic effects were observed in rabbit fetuses at doses up to 10 mg/kg/day (approximately 20-fold the Mutagenesis Advise patients who receive VISUDYNE that they will become temporarily photosensitive after the infusion. Patients should be
recommended human dose of 6 mg/m2, based on body surface area). advised to wear a wrist band to remind them to avoid direct sunlight for 5 days. During that period, patients should be advised
Photodynamic therapy (PDT) as a class has been reported to result in DNA damage including DNA-strand breaks, alkali-labile
8.2 Lactation sites, DNA degradation, and DNA-protein cross-links which may result in chromosomal aberrations, sister chromatid exchanges to avoid exposure of unprotected skin, eyes or other body organs to direct sunlight or bright indoor light. Sources of bright light
(SCE), and mutations. In addition, other photodynamic therapeutic agents have been shown to increase the incidence of SCE in include, but are not limited to, tanning salons, bright halogen lighting and high power lighting used in surgical operating rooms or
Risk Summary dental offices. Prolonged exposure to light from light-emitting medical devices such as pulse oximeters should also be avoided
Chinese hamster ovary (CHO) cells irradiated with visible light and in Chinese hamster lung fibroblasts irradiated with near UV
Verteporfin and its diacid metabolite have been found in human breast milk following an intravenous infusion at the recommended light, increase mutations and DNA-protein cross-linking in mouse L5178 cells, and increase DNA-strand breaks in malignant for 5 days following VISUDYNE administration.
human dose of 6 mg/m2. Verteporfin was present in breast milk at levels up to 66% of the corresponding plasma levels and human cervical carcinoma cells, but not in normal cells. Verteporfin was not evaluated in these latter systems. It is not known how If treated patients must go outdoors in daylight during the first 5 days after treatment, they should be advised to protect all parts of
declined below the limit of quantification (2 ng/mL) within 24 hours. The diacid metabolite had lower peak concentrations but the potential for DNA damage with PDT agents translates into human risk. their skin and their eyes by wearing protective clothing and dark sunglasses. UV sunscreens are not effective in protecting against
persisted up to at least 48 hours. photosensitivity reactions because photoactivation of the residual drug in the skin can be caused by visible light.
Because of the potential for serious adverse reactions in nursing infants from VISUDYNE, a decision should be made whether to Impairment of Fertility
Patients should be advised to not stay in the dark and should be encouraged to expose their skin to ambient indoor light, as it will
discontinue nursing or postpone treatment, taking into account the importance of the drug to the mother. No effect on male or female fertility has been observed in rats following intravenous administration of verteporfin for injection up to help inactivate the drug in the skin through a process called photobleaching.
10 mg/kg/day (approximately 60- and 40-fold human exposure at 6 mg/m2 based on AUC in male and female rats, respectively).
8.4 Pediatric Use Following VISUDYNE treatment, patients should be advised that they may develop visual disturbances such as abnormal vision,
Safety and effectiveness in pediatric patients have not been established. 13.2 Animal Toxicology and/or Pharmacology vision decrease, or visual field defects that may interfere with their ability to drive or use machines. Patients should be advised to
At a >10-fold higher dose given by bolus injection to sedated or anesthetized pigs, verteporfin caused severe hemodynamic not drive or use machines as long as these symptoms persist.
8.5 Geriatric Use effects, including death, probably as a result of complement activation. These effects were diminished or abolished by
Approximately 90% of the patients treated with VISUDYNE in the clinical efficacy trials were over the age of 65. A reduced pretreatment with antihistamine and they were not seen in conscious nonsedated pigs. Manufactured for:
treatment effect was seen with increasing age. Bausch + Lomb, a division of
14 CLINICAL STUDIES Valeant Pharmaceuticals North America LLC
10 OVERDOSAGE
14.1 Age-Related Macular Degeneration (AMD) Bridgewater, NJ 08807 USA
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 Two adequate and well-controlled, double-masked, placebo-controlled, randomized studies were conducted in patients with Manufactured by:
the patient remains photosensitive to bright light. In such cases, it is recommended to extend the photosensitivity precautions for classic-containing subfoveal CNV secondary to AMD. A total of 609 patients (VISUDYNE 402, placebo 207) were enrolled in these Alcami Carolinas Corporation
a time proportional to the overdose. two studies. During these studies, retreatment was allowed every 3 months if fluorescein angiograms showed any recurrence or Charleston, SC 29405 USA
persistence of leakage. The placebo control (sham treatment) consisted of intravenous administration of Dextrose 5% in Water,
followed by light application identical to that used for VISUDYNE therapy. Visudyne is a registered trademark of Novartis AG used under license.
The difference between treatment groups statistically favored VISUDYNE at the 1-year and 2-year analyses for visual All other product/brand names are trademarks of their respective owners.
acuity endpoints.
©Bausch & Lomb Incorporated 9589700