Usage
Methoxsalen is prescribed for the treatment of severe psoriasis, vitiligo, and cutaneous T-cell lymphoma (CTCL) when used in conjunction with ultraviolet A (UVA) light (PUVA therapy). It belongs to the pharmacological classification of psoralens, which are photosensitizing agents. Methoxsalen works by increasing the skin’s sensitivity to UVA light, facilitating the effects of phototherapy in these conditions.
Alternate Names
Methoxsalen is also known as 8-methoxypsoralen (8-MOP). Brand names include Oxsoralen-Ultra, Uvadex, and 8-MOP.
How It Works
Pharmacodynamics: Methoxsalen intercalates with DNA and, upon exposure to UVA light, forms cross-links with pyrimidine bases. This process inhibits DNA synthesis and cell proliferation, suppressing the overactive immune response in psoriasis and promoting melanocyte (pigment-producing cell) proliferation in vitiligo. In CTCL, PUVA and extracorporeal photochemotherapy (photopheresis) are thought to induce apoptosis in malignant T-cells and potentially activate an immune response against them.
Pharmacokinetics:
- Absorption: Oral methoxsalen is well-absorbed, reaching peak plasma concentrations within 1 to 2 hours. Food can enhance absorption.
- Metabolism: Methoxsalen is metabolized in the liver, primarily by CYP3A4.
- Elimination: Primarily eliminated through renal excretion (urine), with a small portion excreted in feces. Approximately 95% of an oral dose is eliminated within 24 hours.
Dosage
Standard Dosage
Adults:
- Psoriasis (oral): Initially, 0.4 to 0.6 mg/kg with food 1.5 to 2 hours before UVA exposure, two to three times per week, with at least 48 hours between treatments. The dose may be increased by 10 mg after 15 treatments if there is minimal response, but this increased dosage should not be exceeded.
- Vitiligo (oral): 20 mg with food 2 to 4 hours before UVA exposure, two to three times per week, with at least 48 hours between treatments.
- CTCL (extracorporeal photochemotherapy): Dose calculated based on treatment volume (Treatment volume x 0.017 ml of Methoxsalen), administered into the photoactivation bag of the UVAR photopheresis system. Treatments are typically given on two consecutive days every 4 weeks.
- Vitiligo (topical): Apply 1% lotion to affected areas 2 hours before UVA exposure, or as prescribed.
Children:
Dosing in children under 12 must be determined by a physician. The safety and efficacy have not been established in this age group for all indications.
Special Cases:
- Elderly Patients: Dose selection should be cautious, starting at the lower end of the dosing range.
- Patients with Renal Impairment: No specific guidelines are available, but caution is advised due to renal elimination.
- Patients with Hepatic Dysfunction: No specific guidelines are available, but caution is advised due to hepatic metabolism. Liver function tests should be monitored.
- Patients with Comorbid Conditions: Caution should be exercised in patients with cardiovascular disease or other conditions that could be exacerbated by PUVA therapy’s potential side effects.
Clinical Use Cases Dosage adjustments and UVA exposure times are condition specific and must be tailored to the patient based on skin type and response to therapy. Clinical use is always in conjunction with UVA irradiation and should be managed by physicians experienced in photochemotherapy.
Dosage Adjustments
Dosage adjustments may be necessary based on individual patient response, renal or hepatic function, and other patient-specific factors.
Side Effects
Common Side Effects:
Nausea, itching, skin redness, nervousness, insomnia, headache, dizziness.
Rare but Serious Side Effects:
Severe sunburn, blistering, skin peeling, skin cancer, cataracts, premature skin aging, eye damage (blurred vision, cataracts), mental/mood changes (depression), peripheral edema.
Long-Term Effects:
Premature skin aging, increased risk of skin cancer.
Adverse Drug Reactions (ADR):
Severe burns, allergic reactions, phototoxicity.
Contraindications
Hypersensitivity to methoxsalen, aphakia, history of melanoma or squamous cell carcinoma, photosensitivity diseases (e.g., lupus, porphyria, xeroderma pigmentosum). Relative contraindications include history of basal cell carcinoma, arsenic therapy, or radiation therapy.
Drug Interactions
Methoxsalen interacts with numerous medications, including certain antibiotics, antifungals, antihypertensives, hormonal contraceptives, and some psychiatric medications. It can also interact with alcohol, grapefruit juice, and other photosensitizing substances. Refer to a drug interaction database for a complete list.
Pregnancy and Breastfeeding
Methoxsalen is classified as FDA Pregnancy Category D, indicating potential fetal risk. It is contraindicated during pregnancy. It is unknown if methoxsalen passes into breast milk, but breastfeeding is not recommended due to potential neonatal photosensitivity.
Drug Profile Summary
- Mechanism of Action: Photosensitizing agent that inhibits DNA synthesis and cell proliferation upon UVA activation.
- Side Effects: Nausea, itching, skin redness, severe sunburn, skin cancer risk, eye damage.
- Contraindications: Hypersensitivity, aphakia, history of skin cancer, photosensitivity disorders.
- Drug Interactions: Numerous drug interactions; consult a database for specifics.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; breastfeeding not recommended.
- Dosage: Varies by condition and patient; see detailed dosage section.
- Monitoring Parameters: Liver function tests, skin reactions, eye exams.
Popular Combinations
Methoxsalen is typically used in combination with UVA light. Other combinations are not commonly utilized.
Precautions
Pre-screening for contraindications is crucial. Patients should be educated about strict sun avoidance and protective measures during and after treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Methoxsalen?
A: The dosage varies depending on the condition, patient age and weight, and administration route. Please refer to the detailed dosage section.
Q2: What are the most serious side effects of Methoxsalen?
A: Severe burns, skin cancer, cataracts, and premature skin aging are potential serious side effects.
Q3: Can Methoxsalen be used during pregnancy?
A: No, Methoxsalen is contraindicated during pregnancy due to potential fetal harm.
Q4: How does Methoxsalen work in vitiligo?
A: Methoxsalen increases the skin’s sensitivity to UVA light, which stimulates melanocyte proliferation and repigmentation of the skin.
Q5: What precautions should patients take while on Methoxsalen?
A: Strict sun protection, including UVA-blocking sunglasses and protective clothing, is essential during and after treatment.
Q6: What are the common drug interactions with Methoxsalen?
A: Methoxsalen interacts with numerous medications. Please refer to a drug interaction database for a complete list.
Q7: What is the difference between oral and topical Methoxsalen?
A: Oral Methoxsalen is used for psoriasis, vitiligo, and CTCL, while topical Methoxsalen is primarily used for localized vitiligo.
A: It is injected into the photoactivation bag of the UVAR photopheresis system, not directly into the patient.
Q9: How long does it take to see results with Methoxsalen?
A: Response times vary. Substantial repigmentation in vitiligo may take 6 to 9 months. Improvement in psoriasis and CTCL also varies depending on the severity of the condition and individual patient response.
