Vitilen

Approved Indications:

• Vitiligo: Treatment of idiopathic and symptomatic vitiligo for repigmentation of depigmented skin.
• Psoriasis: Management of moderate to severe plaque psoriasis unresponsive to conventional therapies, as part of PUVA (Psoralen + UVA) therapy.
• Cutaneous T-cell Lymphoma (CTCL): Palliative treatment of skin manifestations of CTCL (e.g., mycosis fungoides, Sézary syndrome), particularly in early stages.

Clinically Accepted Off-label Uses:

• Alopecia Areata: Used off-label for extensive alopecia areata to stimulate hair regrowth through photochemotherapy.
• Chronic Graft-versus-Host Disease (GVHD): Utilized in extracorporeal photopheresis (ECP) for steroid-refractory chronic GVHD.
• Severe Atopic Dermatitis or Eczema: Considered in severe, chronic cases resistant to other treatments.

Route of Administration: Oral, topical, or intravenous (as part of extracorporeal photopheresis).

Adults:

• Oral PUVA Therapy (for Psoriasis and Vitiligo):
• Dose: 0.6 mg/kg orally, approximately 1.5–2 hours before UVA exposure.
• Typical dose range: 10–70 mg per session.
• Frequency: 2–3 times per week; sessions should be spaced at least 48 hours apart.
• Extracorporeal Photopheresis (CTCL/GVHD):
• Methoxsalen is administered as a 0.01% solution in an ex vivo system.
• Frequency: 2 consecutive days every 2–4 weeks.
• Topical Therapy (Localized Vitiligo):
• Apply methoxsalen solution to depigmented patches.
• UVA exposure should begin 15–30 minutes after application.
• Protect unaffected skin from UVA exposure.

Pediatric Use:

• Not recommended for children under 12 years due to increased sensitivity and long-term risk of skin cancer.

Geriatric Use:

• Use adult dose with caution; monitor for increased photosensitivity and hepatic function.

Renal/Hepatic Impairment:

• Use with caution; no defined dose adjustment, but increased sensitivity may occur.

Administration Notes:

• Administer oral doses with food or milk to minimize gastrointestinal upset.
• Strict UVA timing is essential: 1.5–2 hours post-oral dose.
• Patients must wear UVA-blocking sunglasses for 24 hours post-dose.
• Avoid sunlight for at least 8 hours following ingestion.

Methoxsalen is a psoralen derivative that intercalates into DNA. Upon activation by long-wave ultraviolet A (UVA) light (320–400 nm), it forms covalent bonds with pyrimidine bases, primarily thymine. This results in DNA cross-linking, inhibiting DNA synthesis and cell division. In hyperproliferative conditions like psoriasis and CTCL, this leads to reduced keratinocyte or T-cell proliferation. In vitiligo, UVA-activated methoxsalen stimulates melanocyte activity and melanin production, promoting repigmentation of affected areas.

• Absorption: Rapid oral absorption; peak plasma concentrations occur 1.5–2 hours post-dose.
• Bioavailability: Variable; improved with food.
• Distribution: Widely distributed in tissues; crosses the placenta.
• Metabolism: Primarily metabolized in the liver via cytochrome P450 enzymes (mainly CYP3A4).
• Half-life: Approximately 0.5 to 2 hours.
• Excretion: Primarily excreted in urine as inactive metabolites; minor fecal excretion.
• Onset of Action: Therapeutic effects may take several weeks.

• Pregnancy: Category C (US FDA)
• Animal studies show fetal harm. Human data is limited. Use only if benefits clearly outweigh risks.
• Lactation:
• Unknown if excreted in breast milk. Due to potential photosensitization, breastfeeding should be avoided for 24 hours after administration.
• Recommendation: Avoid during pregnancy and breastfeeding unless absolutely necessary.

• Primary Class: Photosensitizing agent
• Subclass: Psoralen derivative (used in PUVA therapy)

• Known hypersensitivity to methoxsalen or other psoralens
• History of light-sensitive disorders (e.g., lupus erythematosus, porphyria, albinism)
• Current or previous melanoma or invasive skin cancer
• Aphakia (due to risk of retinal damage)
• Severe hepatic impairment
• Pregnancy and breastfeeding
• Children under 12 years of age

• Skin Cancer Risk: Increased risk of squamous cell carcinoma and melanoma with prolonged PUVA therapy.
• Ocular Risk: Risk of cataract formation; protective UVA eyewear required for 24 hours after administration.
• Photosensitivity: Strict sun avoidance for at least 8 hours post-administration.
• Hepatic Monitoring: Use cautiously in hepatic impairment; methoxsalen metabolism may be impaired.
• Clinical Monitoring: Regular dermatologic and ophthalmologic exams are recommended during long-term therapy.
• Delayed Response: Pigmentation may take weeks; do not discontinue prematurely without evaluation.

Common Adverse Effects:

• Dermatologic: Erythema, itching, burning, dryness, blistering, hyperpigmentation
• Gastrointestinal: Nausea, vomiting, anorexia
• Neurological: Dizziness, headache
• Ocular: Photophobia, blurred vision

Serious Adverse Effects:

• Skin aging, actinic keratoses
• Nonmelanoma skin cancers (with prolonged use)
• Melanoma (long-term risk)
• Cataracts (especially in aphakic patients)
• Hepatotoxicity (rare)

Onset: Most adverse effects occur within 24–72 hours of UVA exposure; long-term effects (e.g., carcinogenesis) may appear years later.

• Photosensitizing drugs (e.g., tetracyclines, sulfonamides, fluoroquinolones): Increased phototoxic risk
• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): May increase methoxsalen plasma levels and toxicity
• CYP3A4 inducers (e.g., rifampin, phenytoin): May reduce therapeutic efficacy
• Alcohol: May exacerbate hepatotoxicity
• Anticoagulants: Use cautiously due to potential liver effects affecting coagulation factors

• FDA Update: Methoxsalen in extracorporeal photopheresis remains approved for CTCL and GVHD under strict institutional protocols.
• AAD Guidelines (2023): Recommend lowest effective cumulative UVA dose to minimize long-term cancer risk.
• EMA Safety Notice: Emphasizes mandatory use of UVA-protective eyewear and routine skin cancer screening in long-term users.

• Oral Capsules:
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from light and moisture
• Keep tightly closed in original container
• Topical Solution:
• Store at 2°C to 8°C (refrigerator); do not freeze
• Protect from direct light
• Use under medical supervision
• Injectable (for ECP):
• Store at 2°C to 8°C
• Protect from light
• Discard unused portion after use
• Handling Precautions:
• Wear gloves during handling
• Avoid direct exposure to light and skin contact
• Patients must avoid sunlight exposure after administration