Usage
Verteporfin, in conjunction with photodynamic therapy (PDT), is primarily indicated for the treatment of:
- Subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), pathologic myopia, or presumed ocular histoplasmosis.
- Central serous chorioretinopathy (off-label use).
Pharmacological Classification: Photosensitizing agent.
Mechanism of Action: Verteporfin is a light-activated drug. When exposed to non-thermal red light of a specific wavelength (689 nm), it produces reactive oxygen species that damage the abnormal blood vessels in the eye associated with CNV, thereby reducing vascular leakage and slowing the progression of vision loss.
Alternate Names
International Nonproprietary Name (INN): verteporfin
Brand Name: Visudyne
How It Works
Pharmacodynamics: Verteporfin selectively accumulates in neovascular endothelial cells. Upon activation with non-thermal red light, it triggers the formation of reactive oxygen species, leading to localized vascular damage and occlusion of the targeted CNV. This reduces vascular permeability and inhibits further growth of abnormal blood vessels.
Pharmacokinetics:
- Absorption: Administered intravenously.
- Distribution: Transported in plasma primarily by lipoproteins, preferentially accumulating in neovascular endothelial cells.
- Metabolism: Rapidly metabolized to a diacid metabolite.
- Elimination: Primarily eliminated in feces (about 90%) with minimal urinary excretion (less than 1%). The half-life is less than 5 hours.
Mode of Action: Receptor-independent; activation by light generates reactive oxygen species.
Elimination Pathways: Primarily fecal; minimal renal. No significant CYP enzyme involvement is reported.
Dosage
Standard Dosage
Adults:
6 mg/m² body surface area administered as an intravenous infusion over 10 minutes. Photoactivation with non-thermal red light (689 nm, 50 J/cm², 600 mW/cm²) is initiated 15 minutes after the start of the infusion and lasts for 83 seconds. Retreatment may be necessary every 3 months if CNV leakage recurs, up to a maximum of four treatments per year.
Children:
Safety and efficacy in pediatric patients have not been established.
Special Cases:
- Elderly Patients: No specific dose adjustment is required, but a reduced treatment effect has been observed with increasing age.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Caution is advised in mild to moderate hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with porphyria.
Clinical Use Cases
Verteporfin is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its use is limited to ophthalmological settings for the treatment of CNV.
Dosage Adjustments:
Dose adjustment may be required in patients with hepatic dysfunction. No dose adjustment is needed for elderly or renally impaired patients.
Side Effects
Common Side Effects:
- Injection site reactions (pain, swelling, discoloration)
- Back pain (during infusion)
- Visual disturbances (blurred vision, decreased vision, flashes of light, visual field defects)
- Dry eyes, itching, increased light sensitivity
- Headache, dizziness
- Nausea, constipation
- Muscle pain or weakness
Rare but Serious Side Effects:
- Severe vision loss
- Allergic reactions (including anaphylaxis)
- Severe injection site reactions (extravasation with necrosis)
Long-Term Effects:
Not extensively studied, but potential for chronic visual disturbances exists.
Adverse Drug Reactions (ADR):
Anaphylaxis, severe vision loss, extravasation with necrosis.
Contraindications
- Porphyria
- Known hypersensitivity to verteporfin or any component of the formulation
- Severe hepatic impairment
Drug Interactions
- Photosensitizing agents: Concomitant use of other photosensitizing medications (e.g., tetracyclines, sulfonamides, phenothiazines, griseofulvin) may increase the risk of photosensitivity reactions.
- Drugs affecting oxygen radicals: Medications that reduce active oxygen species or scavenge radicals (e.g., antioxidants, vasodilators) may decrease verteporfin’s therapeutic effect.
- Other potential interactions: Consult a comprehensive drug interaction resource for a full list of interacting medications, as numerous moderate and minor interactions have been reported.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C (US FDA - prior to new labeling requirements). Animal studies have shown adverse effects. Use only if potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Verteporfin and its metabolite are excreted in breast milk. Breastfeeding should be discontinued for 48 hours after administration.
Drug Profile Summary
- Mechanism of Action: Light-activated photosensitizing agent that damages neovascular endothelial cells.
- Side Effects: Visual disturbances, injection site reactions, photosensitivity, back pain.
- Contraindications: Porphyria, hypersensitivity, severe hepatic impairment.
- Drug Interactions: Photosensitizing agents, drugs affecting oxygen radicals.
- Pregnancy & Breastfeeding: Use with caution in pregnancy; discontinue breastfeeding for 48 hours after administration.
- Dosage: 6 mg/m² IV over 10 minutes, followed by photoactivation.
- Monitoring Parameters: Visual acuity, liver function tests, injection site.
Popular Combinations:
Verteporfin is not typically used in combination with other drugs for CNV treatment.
Precautions
- General Precautions: Avoid extravasation during infusion. Patients will become photosensitive for 48 hours after administration; protect from sunlight and bright indoor light. Monitor visual acuity and liver function tests.
- Specific Populations: See section on Dosage - Special Cases.
- Lifestyle Considerations: Advise patients to avoid direct sunlight and bright indoor lights for 48 hours after treatment. Driving may be impaired due to visual disturbances.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Verteporfin?
A: 6 mg/m² body surface area infused intravenously over 10 minutes, followed by photoactivation with non-thermal red light 15 minutes after the start of the infusion.
Q2: How often can Verteporfin be administered?
A: Treatment may be repeated every 3 months if necessary, up to four times per year.
Q3: What are the main contraindications to Verteporfin therapy?
A: Porphyria, known hypersensitivity to verteporfin, and severe hepatic impairment.
Q4: What are the most common side effects of Verteporfin?
A: Visual disturbances, injection site reactions, back pain during infusion, and photosensitivity.
Q5: How does Verteporfin work?
A: It’s a photosensitizing agent. When activated by light, it generates reactive oxygen species that damage abnormal blood vessels in the eye.
Q6: Can Verteporfin be used during pregnancy?
A: It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Q7: What precautions should be taken after Verteporfin administration?
A: Patients should avoid exposure to sunlight and bright indoor lights for 48 hours. Monitor for vision changes.
Q8: Are there any drug interactions with Verteporfin?
A: Yes, it can interact with other photosensitizing medications and drugs affecting oxygen radicals. Consult a comprehensive drug interaction resource for detailed information.
Q9: How is Verteporfin eliminated from the body?
A: Primarily through fecal excretion.
