Visudyne

Generic Name: Verteporfin
Class: EENT Drugs, Miscellaneous
VA Class: OP900
Molecular Formula: C41H42N4O8
CAS Number: 129497-78-5

Introduction

Photosensitizing agent activated by low-intensity laser light; synthetic benzoporphyrin derivative.1 2 3 4 5 6 7

Uses for Visudyne

Subfoveal Choroidal Neovascularization

Treatment of predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration,1 2 3 4 5 6 7 9 pathologic myopia,1 10 11 or presumed ocular histoplasmosis.1 11 12 Use in combination with nonthermal red light (i.e., photodynamic therapy).1 2 3 4 5 6 7 9 10 11 12

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Insufficient evidence to establish efficacy for treatment of predominantly occult subfoveal choroidal neovascularization.1

Not recommended for use in the less severe, dry form of macular degeneration in which neovascularization is not present.4 6 7 8

Visudyne Dosage and Administration

General

  • Photodynamic therapy with verteporfin is a 2-step process that requires IV administration of the drug followed by activation of verteporfin with light from a nonthermal diode laser.1 2 3 4 5 6 7 (See Administration under Dosage and Administration.)

Lesion Size Determination

  • Estimate the greatest linear dimension (GLD) of the lesion (i.e, all classic and occult choroidal neovascularization, blood and/or blocked fluorescence, and any serous detachments of the retinal pigment epithelium) by fluorescein angiograph and color fundus photography; correct for the magnification of the fundus camera to obtain the GLD of the lesion on the retina.1

  • Fundus cameras with a magnification of 2.4–2.6X recommended.1

Spot Size Determination

  • Treatment spot size should be 1000 mcm larger than the GLD of the lesion on the retina to allow a 500-mcm border and ensure full coverage of the lesion.1

  • Position the nasal edge of the treatment spot at least 200 mcm from the temporal edge of the optic disc, even if this will result in lack of exposure of choroidal neovascularization within 200 mcm of the optic nerve.1

Concurrent Bilateral Treatment

  • Patients with eligible lesions in both eyes may be candidates for concurrent treatment; evaluate potential risks and benefits of treating both eyes concurrently.1

  • For patients who previously have received photodynamic therapy in one eye without adverse sequelae, both eyes can be treated concurrently provided there are eligible lesions in both eyes and the potential benefits outweigh the risks.1

  • In patients with eligible lesions in both eyes who have not previously received photodynamic therapy, treat one eye first (the one with the most aggressive lesion).1 If treatment is well tolerated, treat the second eye 1 week later.1 Evaluate both eyes approximately 3 months later, and initiate concurrent treatment if indicated.1

Administration

IV Administration

Administer by IV infusion using an appropriate syringe pump and inline filter with a pore size of 0.22–1.2 mcm.1 8

Protect diluted solution from bright light during administration.1 8

Avoid contact of verteporfin solution with the eyes and skin during preparation and administration; potential for photosensitivity reactions upon exposure to light.1 (See Sensitivity Reactions under Cautions.) Wipe up spills with a damp cloth; rubber gloves and eye protection recommended.1

Avoid extravasation; severe pain, inflammation, swelling, or discoloration may occur, especially if affected area is exposed to light.1 Establish a free-flowing IV line prior to administration, avoid small veins in the back of the hand, and use the largest vein possible (e.g., antecubital vein) in geriatric patients.1 If extravasation occurs, immediately stop infusion and thoroughly protect extravasation area from direct light until swelling and discoloration have faded.1 (See Local Effects under Cautions.)

Observe patient during infusion because serious reactions can occur.1 (See Sensitivity Reactions under Cautions.)

Reconstitution

Reconstitute vial containing 15 mg of verteporfin powder with 7 mL of sterile water for injection to provide a solution containing 2 mg/mL.1

Protect reconstituted solution from bright light during administration; use reconstituted solution within 4 hours.1 8

Dilution

Following reconstitution, dilute appropriate dose with 5% dextrose injection to a total volume of 30 mL.1

Rate of Administration

3 mL per minute.1

Photoactivation

Initiate application of light 15 minutes after the start of the verteporfin infusion using a diode laser at 689 nm wavelength.1

The recommended light dose is 50 J/cm2 of neovascular lesion administered at an intensity of 600 mW/cm2 over 83 seconds.1 5

If both eyes are treated concurrently, initiate light application 15 minutes after the start of the infusion in the eye with the more aggressive lesion.1 At the end of the light application to the first eye, apply the same light dose and intensity as used in the first eye to the second eye; initiate light application to the second eye no later than 20 minutes after the start of the infusion.1

Light dose, light intensity, ophthalmic lens magnification factor, and zoom lens setting are important parameters for the appropriate delivery of light to the predetermined treatment spot.1

Dosage

Adults

Subfoveal Choroidal Neovascularization
IV

6 mg/m2.1

Photodynamic therapy can be repeated every 3 months.1 3 4 5 6

Prescribing Limits

Adults

Subfoveal Choroidal Neovascularization
IV

Safety and efficacy ≥ 2 years not established.1

Cautions for Visudyne

Contraindications

  • Porphyria.1

  • Known hypersensitivity to verteporfin or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Local Effects

Extravasation produces severe pain, inflammation, swelling, or discoloration, especially if affected area is exposed to light.1 Protect extravasation area from direct light until swelling and discoloration have faded in order to prevent the occurrence of a potentially severe local burn.1

If extravasation occurs, discontinue infusion and apply cold compresses; may administer oral pain medications.1

Ocular Effects

Severe vision decrease (i.e., loss of ≥4 lines) within 1 week of therapy reported.1 Partial recovery of vision observed in some patients.1 Patients who experience a loss of ≥4 lines of visual acuity within 1 week of therapy should not be retreated until their vision recovers to pretreatment levels, and the risks and benefits are carefully considered.1

Visual disturbances (e.g., blurred vision, decreased visual acuity, visual field defect) reported in patients with age-related macular degeneration.8 9

Possible collateral damage to retinal structures (e.g., retinal pigmented epithelium, outer nuclear retinal layer) following photoactivation since the drug may distribute into the retina.1 6 (See Distribution under Pharmacokinetics.)

Laser Selection

Use of incompatible lasers that do not provide the required characteristics of light for photoactivation of verteporfin could result in incomplete treatment due to partial photoactivation of verteporfin, overtreatment due to overactivation of verteporfin, or damage to surrounding normal tissue.1

Sensitivity Reactions

Photosensitivity

Potential for photosensitivity reactions (e.g., sunburn) upon exposure to light.1

Avoid exposure of skin and eyes to direct sunlight, bright indoor light (e.g., tanning salons, bright halogen lighting, high-power lighting used in operating rooms or dental offices), or prolonged exposure to light from a light-emitting medical device (e.g., pulse oximeter) for 5 days following administration of verteporfin.1

Protect internal tissue from intense light if emergency surgery is necessary within 48 hours of verteporfin administration.1

Complement Activation

Manifestations (chest pain, syncope, dyspnea, flushing) consistent with complement activation reported in <1% of patients.1 10 13 Patients should be observed during infusion.1

In animal studies, severe hemodynamic effects, including death, observed in anesthetized pigs.1 Effects diminished or abolished by pretreatment with an antihistamine.1 Verteporfin not studied in anesthetized humans.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not know whether verteporfin distributed into human milk.1 Caution if used in nursing women.1

Pediatric Use

Safety and efficacy not established.1 8

Geriatric Use

Approximately 90% of patients in clinical studies were ≥65 years of age.1 2 3 5 Efficacy is reduced with increasing age (e.g., ≥75 years of age).1

Hepatic Impairment

Not evaluated in patients with moderate to severe hepatic impairment or biliary obstruction; use with caution.1 (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Injection site reactions, visual disturbances.1

Interactions for Visudyne

Not metabolized by CYP-450 isoenzymes.1

No formal drug interactions studies in humans to date.1

Compounds That Quench Active Oxygen Species or Scavenge Radicals

Possible decreased verteporfin activity with concomitant use of these agents (e.g., alcohol, beta carotene, dimethylsulfoxide, formate, mannitol).1

Drugs That Decrease Clotting, Vasoconstriction, or Platelet Aggregation

Possible decreased efficacy of verteporfin therapy.1

Specific Drugs

Drug

Interaction

Calcium-channel blocking agents

Possible enhanced rate of verteporfin uptake by vascular endothelium1

Diuretics, thiazide

Increased potential for photosensitivity reactions1

Griseofulvin

Increased potential for photosensitivity reactions1

Phenothiazines

Increased potential for photosensitivity reactions1

Polymyxin B

Possible enhanced rate of verteporfin uptake by vascular endothelium1

Radiation therapy

Possible enhanced rate of verteporfin uptake by vascular endothelium1

Sulfonamides

Increased potential for photosensitivity reactions1

Sulfonylurea hypoglycemic agents

Increased potential for photosensitivity reactions1

Tetracyclines

Increased potential for photosensitivity reactions1

Visudyne Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations occur at end of infusion.15

Distribution

Extent

Accumulates preferentially in neovasculature, including choroidal neovasculature.1 Also distributed to the retina in animals.1

Elimination

Metabolism

Metabolized to a small extent by liver and plasma esterases to a pharmacologically active diacid metabolite.1 8

Elimination Route

Rapidly eliminated principally via biliary excretion in feces as unchanged drug.1 15

Half-life

Terminal half-life is approximately 5–6 hours.1 15

Special Populations

Half-life increased by 20% in patients with mild hepatic impairment.1

Stability

Storage

Parenteral

Powder for Injection

20–25°C.1

Protect reconstituted solutions from bright light.1 Use reconstituted solution within 4 hours.1 8 Following dilution with infusion solution, the drug is stable for up to 4 hours.8

Actions

  • A component of photodynamic therapy.1 2 4 5 6

  • Activated by light in the presence of oxygen, resulting in a physiochemical event that can be used to selectively damage pathologic structures.1 2 3 4 5 6 Activation leads to generation of highly reactive, short-lived singlet oxygen and reactive oxygen intermediates that cause local cytotoxic effects.1 2 4 5 6

  • Light activation of the drug in the eye results in local damage to the neovascular endothelial cells, which leads to temporary occlusion of choroidal neovasculature.1 2 3 4

Advice to Patients

  • Importance of avoiding exposure of unprotected skin, eyes, or other body organs to direct sunlight, bright indoor light, or prolonged exposure to light from a light-emitting medical device for 5 days.1

  • Importance of wearing a wrist band to remind patient to avoid direct sunlight and to alert health professionals about the patient’s exposure to a photosensitizing drug within the past 5 days.1 8

  • Importance of protecting all parts of skin and eyes by wearing protective clothing and dark sunglasses if the patient must go outdoors during the first 5 days after treatment.1 UV sunscreens do not prevent photosensitivity reactions, since photoactivation of residual drug in skin can be caused by visible light.1

  • Importance of not staying in the dark since exposure of skin to ambient indoor light helps inactivate the drug.1

  • Importance of providing patient a copy of manufacturer’s patient information.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Verteporfin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection concentrate, for IV infusion only

15 mg

Visudyne

QLT, (also promoted by Novartis)

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Novartis. Visudyne (verteporfin for injection) prescribing information. East Hanover, NJ; 2004 Sep.

2. Miller JW, Schmidt-Erfurth U, Sickenberg M et al. Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of a single treatment in a phase 1 and 2 study. Arch Ophthalmol. 1999; 117:1161-73. [IDIS 434839] [PubMed 10496388]

3. Schmidt-Erfurth U, Miller JW, Sickenberg M et al. Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study. Arch Ophthalmol. 1999; 117:1177-87. [IDIS 434840] [PubMed 10496389]

4. Fine SL. Photodynamic therapy with verteporfin is effective for selected patients with neovascular age-related macular degeneration. Arch Ophthalmol. 1999; 117:1400-2. [IDIS 436690] [PubMed 10532450]

5. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report 1. Arch Ophthalmol. 1999; 117:1329-45. [IDIS 436688] [PubMed 10532441]

6. Scott LJ, Goa KL. Verteporfin. Drugs Aging. 2000; 16:139-46. [PubMed 10755329]

7. Anon. FDA approves treatment for wet macular degeneration. HHS News. P00-9. Rockville, MD: Food and Drug Administration; 2000 Apr 13.

8. Ciba Vision, Duluth, GA: Personal communication.

9. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials—TAP report 2. Arch Ophthalmol. 2001; 119:198-207. (IDIS 459053) [IDIS 459053] [PubMed 11176980]

10. Verteporfin in Photodynamic Therapy (VIP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin: 1-year results of a randomized clinical trial—VIP report no. 1. Ophthamol. 2001; 108:841-52. (IDIS 463277)

11. Sickenberg M, Schmidt-Erfurth U, Miller JW et al. A preliminary study of photodynamic therapy using verteporfin for choroidal neovascularization in pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. Arch Ophthalmol. 2000; 117:327-36. (IDIS 444487)

12. Saperstein DA, Rosenfeld PJ, Bressler NM et al. Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin in the ocular histoplasmosis syndrome: one-year results of an uncontrolled prospective case series. Ophthalmol. 2002; 109:1499-505.

13. Cahill MT, Smith BT, Fekrat S. Adverse reaction characterized by chest pain, shortness of breath, and syncope associated with verteporfin (Visudyne). Am J Ophthalmol. 2002; 134;281-2. (IDIS 484479) [IDIS 484479] [PubMed 12140044]

14. Noffke AS, Jampol LM, Weinberg DV et al. A potential life-threatening adverse reaction to verteporfin. Arch Ophthalmol. 2001; 119:143. Letter. [IDIS 457848] [PubMed 11146745]

15. Houle JM, Strong A. Clinical pharmacokinetics of verteporfin. J Clin Pharmacol. 2002; 42:547-57. [PubMed 12017349]

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