Verteporfin

Uses

Verteporfin therapy is used for the treatment of patients with predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis.There is insufficient evidence to indicate Verteporfin for the treatment of predominantly occult subfoveal choroidal neovascularization.

Verteporfin is also used to associated treatment for these conditions: Subfoveal Choroidal Neovascularization

How Verteporfin works

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 lipo-oxygenase (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. As singlet oxygen and reactive oxygen radicals are cytotoxic, Verteporfin can also be used to destroy tumor cells.

Dosage

Verteporfin dosage

A course of verteporfin therapy is a two-step process requiring administration of both drug and light. The first step is the intravenous infusion of Verteporfin. The second step is the activation of Verteporfin with light from a nonthermal diode laser. The physician should reevaluate the patient 3 months after treatment and if choroidal neovascular leakage is detected onfluorescein angiography, therapy may be repeated.Lesion Size Determination: The greatest linear dimension (GLD) of thelesionshould be estimated by fluoresceinangiographyand color fundus photography. All classic and occult CNV, blood and/or blocked fluorescence, and any serous detachments of theretinal 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 theretina.Spot Size Determination: The treatment spot size should be 1000 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 6400 microns.Thenasaledge of the treatment spot must be positioned at least 200 microns from the temporal edge of theoptic disc, even if this will result in lack of photoactivation of CNV within 200 microns of theoptic nerve.

Side Effects

Visual disturbances; severe vision loss with or without subretinal or vitreous bleeding; inj site reactions; nausea; photosensitivity; asthenia; cataracts; blepharitis; conjunctivitis; dry eyes; ocular itching; flu-like syndrome; atrial fibrillation; hypertension; peripheral vascular disorder; varicose veins; eczema; constipation; Gl cancers; fever; lachrymation disorder; hypersensitivity reactions; increased LFT.

Toxicity

Overdose of drug and/or light in the treated eye may result in nonperfusion 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.

Precaution

Moderate to severe hepatic disorders; biliary disorders. Pregnancy. Use the largest arm vein possible (e.g. antecubital) especially in elderly and avoid small veins in the back of the hand. Stop infusion if extravasation occurs and protect extravasation area from direct light and apply cold compresses. Patient to be under close monitoring during verteporfm infusion and exercise caution when general anaesthesia is considered. Avoid exposure of unprotected skin, eyes or other body organs to direct sunlight or bright indoor light for 5 days after treatment. Protect all parts of skin and eyes by wearing protective clothing and dark sunglasses (sunscreens are ineffective) if going outdoors in daylight is necessary. Exposure to ambient indoor light is encouraged as it helps in gradual inactivation of any remaining drug.

Interaction

Increased rate of verteporfm uptake by the vascular endothelium with calcium channel blockers, polymyxin B or radiation therapy. Increased photosensitivity with photosensitizing agents (e.g. tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycaemic agents, thiazide diuretics and griseofulvin). Decreased verteporfm efficacy with compounds that quench active oxygen species or scavenge radicals e.g. dimethyl sulfoxide, betacarotene, ethanol, formate and mannitol. Decreased verteporfm efficacy with drugs that decrease clotting, vasoconstriction or platelet aggregation e.g. thromboxane A2 inhibitors. Anaesthetics may cause haemodynamic effects.

Food Interaction

Verteporfin Alcohol interaction

[Moderate]

Drugs that quench active oxygen species or scavenge radicals are expected to decrease the therapeutic effect of verteporfin.

The clinician should carefully assess the patient for desired benefits and risks before beginning verteporfin therapy.

Verteporfin Drug Interaction

Unknown: charcoal, proparacaine ophthalmic, nedocromil ophthalmic, bevacizumab, azithromycin ophthalmic, brinzolamide ophthalmic, povidone iodine ophthalmic, levobetaxolol ophthalmic, betaxolol ophthalmic, arginine, levocarnitine, cysteine, lithium, valproic acid, thiamine, cyanocobalamin, pyridoxine, cholecalciferol, phytonadione, menaquinone

Verteporfin Disease Interaction

Major: porphyriaModerate: hepatic impairment

Half Life

Following intravenous infusion, verteporfin exhibits a bi-exponential elimination with a terminal elimination half-life of approximately 5-6 hours. Mild hepatic insufficiency increases half-life by approximately 20%.

Elimination Route

Elimination is by the fecal route, with less than 0.01% of the dose recovered in urine.

Pregnancy & Breastfeeding use

Pregnancy Category- C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

Contraindication

Verteporfin is contraindicated for patients with porphyria or a known hypersensitivity to any component of Verteporfin

Special Warning

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.Geriatric Use: Approximately 90% of the patients treated with Verteporfin in the clinical efficacy trials were over the age of 65. A reduced treatment effect was seen with increasing age.

Acute Overdose

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.

Innovators Monograph

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