Verteporfin

Registered South African indications

• Age-related macular degeneration (AMD) with classic subfoveal choroidal neovascularisation (CNV)

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe hepatic impairment
• Pre-existing porphyria

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Moderate hepatic impairment
• Biliary obstruction
• Exposure to direct sunlight or bright indoor light
• Prolonged exposure to light emitting medical devices
• Infusion into small veins
• General anaesthesia
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Age-related macular degeneration with classic subfoveal choroidal neovascularisation
Exudative (wet) age-related macular degeneration (AMD) with predominantly classic subfoveal choroidal neovascularisation (CNV)
Subfoveal choroidal neovascularisation secondary to pathological myopia

• IV: Initial: 6mg/m², diluted in 30ml infusion solution, infused over 10min; Then: Light activation 15mins after the start of infusion; Treatment duration: 4 times/year

Patients should be re-evaluated every 3 months

Verteporfin should be administered only by ophthalmologists experienced in the management of patients with age-related macular degeneration or with pathological myopia

See additional prescribing points

Not established for use in children

Pregnancy

• Caution
• No clinical data on exposed pregnancies are available for verteporfin
• Studies in animals have shown teratogenic effects in one species (rat). The potential risk for humans is unknown
• Verteporfin should not be used during pregnancy unless clearly necessary (only if the benefit justifies the potential risk to the foetus)

Breastfeeding

• Caution; not recommended
• Verteporfin and its diacid metabolites are excreted in human milk in low amounts
• It should therefore not be administered to breastfeeding mothers, or breastfeeding should be interrupted for 48 hours after administration

Fertility

• There is no human fertility data for verteporfin
• In non-clinical studies, no impairment of fertility and no genotoxicity have been observed. The clinical relevance is unknown
• Patients of reproductive age should be made aware of the lack of fertility data, and verteporfin should only be given after consideration of individual risks and benefits

Renal Impairment

• Caution; no information available
  Verteporfin has not been studied in patients with renal impairment. However, the pharmacological characteristics do not indicate any need to adjust the dose

Hepatic Impairment 

• Mild: No dose adjustment recommended
• Moderate: Caution; no information available
  Verteporfin therapy should be considered carefully in patients with moderate hepatic impairment or biliary obstruction
• Severe: Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Syncope
• Headache
• Dizziness
• Hyperaesthesia
• Vasovagal reactions
• Asthenia

Cardiovascular Disorders

• Myocardial infarction
• Hypertension
• Chest pain

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders

• Nausea

Endocrine and Metabolic Disorders

• Hypercholesteraemia

Musculoskeletal Disorders

• Back pain

Skin and Subcutaneous Tissue Disorders

• Photosensitivity reaction
• Rash
• Urticaria
• Pruritus
• Injection site pain
• Injection site oedema
• Injection site inflammation
• Injection site extravasation
• Injection site hypersensitivity
• Injection site haemorrhage
• Injection site discolouration
• Injection site vesicles
• Injection site necrosis

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
  - Headache
  - Malaise
  - Syncope
  - Sweating
  - Dizziness
  - Rash
  - Pruritis
  - Urticaria
  - Dyspnoea
  - Flushing
  - Changes in blood pressure
  - Changes in heart rate
  - Convulsions
• Anaphylactic reaction
• Fever

Sensory Disorders

• Severely reduced visual acuity
• Visual impairment
• Blurred vision
• Fuzzy vision
• Photopsia
• Visual field defect
• Scotoma
• Grey or dark haloes and black spots
• Retinal detachment
• Retinal haemorrhage
• Vitreous haemorrhage
• Retinal oedema
• Retinal ischaemia (retinal or choroidal vessel non-perfusion)
• Retinal pigment epithelial tear
• Macular oedema

• Other photosensitising medicinal products
• Tetracyclines
• Sulphonamides
• Phenothiazines
• Sulfonylurea
• Hypoglycaemic agents
• Thiazide diuretics
• Griseofulvin
• Agents which increase uptake in the vascular endothelium
• Calcium channel blockers
• Polymixin B
• Radiation therapy
• Antioxidants
• Beta-carotene
• Medicinal products which scavenge free radicals
• Dimethylsulfoxide
• Formate
• Mannitol
• Alcohol
• Vasodilators
• Agents which diminish clotting and platelet aggregation
• Thromboxane A2 inhibitors

•  Fluorescein angiography

Treatment of the second eye with verteporfin

• There is no clinical data to support concomitant treatment of the second eye
• However, if treatment of the second eye is deemed necessary, light should be applied to the second eye immediately after light application in the first eye but no later than 20 minutes from the start of the infusion

Incompatibilities

• Verteporfin precipitates in sodium chloride solution. Do not use normal sodium chloride or other parenteral solutions

Photosensitivity and exposure to light

• Patients who receive verteporfin will become photosensitive for 48 hours after the infusion
• During that period, patients should avoid exposure of unprotected skin, eyes or other body organs to direct sunlight or bright indoor light such as tanning salons, bright halogen lighting, or high power lighting in surgery operating rooms or dental surgeries
• Prolonged exposure to light from light-emitting medical devices such as pulse oximeters should also be avoided for 48 hours following verteporfin administration
• If patients have to go outdoors in daylight during the first 48 hours of treatment, they must protect their skin and eyes by wearing protective clothing and dark sunglasses. UV sunscreens are not effective in protecting against photosensitivity reactions
• Ambient indoor light is safe. Patients should not stay in the dark and should be encouraged to expose their skin to ambient indoor light, as it will help eliminate the medicinal product quickly through the skin by a process called photobleaching

Verteporfin, also referred to as benzoporphyrin derivative monoacids (BPD-MA) consists of a 1:1 mixture of the equally active regioisomers BPD-MAc and BPD-MAd. It is used as a light-activated medicinal product (photosensitiser). By itself, the clinically recommended dose of verteporfin is not cytotoxic. It produces cytotoxic agents only when activated by light in the presence of oxygen. When energy absorbed by the porphyrin is transferred to oxygen, highly reactive short-lived singlet oxygen is generated. Singlet oxygen causes damage to biological structures within the diffusion range, leading to local vascular occlusion, cell damage and, under certain conditions, cell death. The selectivity of PDT using verteporfin is based, in addition to the localised light exposure, on selective and rapid uptake and retention of verteporfin by rapidly proliferating cells including the endothelium of choroidal neovasculature.

Injection (per vial) 15mg

• Visudyne (Novartis) originator