Methoxsalen

It is indicated for the repigmentation of idiopathic vitiligo. It is also indicated for the symptomatic control of severe, recalcitrant, disabling psoriasis not adequately responsive to other forms of therapy and when the diagnosis has been supported by biopsy.

The combination treatment regimen of Psoralen (P) and UVA (Ultraviolet radiation of 320-400 nm wavelength) is commonly known as PUVA. Skin reactivity to UVA radiation is enhanced by the ingestion of Methoxsalen. The drug reaches its maximum bioavailability 1-3 hours after oral administration and may last for up to 8 hours. Methoxsalen is reversibly bound to serum albumin and is also preferentially taken up by epidermal cells. In both mice and man, Methoxsalen is rapidly metabolized. Approximately 95% of the drug is excreted as a series of metabolites in the urine within 24 hours.

The exact mechanism of action of Methoxsalen with the epidermal melanocytes and keratinocytes is not known. The best known biochemical reaction of Methoxsalen is with DNA. Methoxsalen, upon photoactivation, conjugates and forms covalent bonds with DNA (both monofunctional and bifunctional). Reactions with proteins have also been described.

Methoxsalen capsules:

Vitiligo therapy: Two Methoxsalen capsules (10 mg each) in one dose taken with milk or food two to four hours before ultraviolet light exposure.

Light exposure: The exposure time to sunlight should comply with the following guide:

• Initial exposure: Light-15 min, Medium-20 min, Dark-25 min
• Second exposure: Light-20 min, Medium-25 min, Dark-30 min
• Third exposure: Light-25 min, Medium-30 min, Dark-35 min
• Fourth exposure: Light-30 min, Medium-35 min, Dark-40 min

Subsequent exposure: Gradually increase exposure based on erythema and tenderness of the amelanotic skin. Therapy should be on alternate days and never two consecutive days.

Psoriasis therapy: The Methoxsalen capsules should be taken 2 hours before UVA exposure with some food or milk, according to the following table:

• <30 kg body weight: 10 mg
• 30-50 kg body weight: 20 mg
• 51-65 kg body weight: 30 mg
• 66-80 kg body weight: 40 mg
• 81-90 kg body weight: 50 mg
• 91-115 kg body weight: 60 mg
• >115 kg body weight: 70 mg

Methoxsalen Lotion: is applied to a well-defined area of vitiligo by the physician and the area is then exposed to a suitable credit of UVA. Initial exposure time should be conservative and not exceed that which is predicted to be one-half the minimal erythema dose. Treatment intervals should be regulated by the erythema response; generally once a week is recommended or less often depending on results. The hands and fingers of the person applying the medication should be protected by gloves or finger cots to avoid photosensitization and possible burns.

Pigmentation may begin after a few weeks but significant repigmentation may require 6 to 9 months of treatment. Periodic re-treatment may be necessary to retain all of the new pigment. Idiopathic vitiligo is reversible but not equally reversible in every patient. Treatment must be individualized. Repigmentation will vary in completeness, time of onset, and duration. Repigmentation occurs more rapidly in fleshy areas such as face, abdomen, and buttocks and less rapidly over less fleshy areas such as the dorsum of the hands or feet.

Hands and fingers of person applying the lotion should be protected to prevent possible photosensitization and/or burns.

May increase plasma concentration of drugs metabolised by CYP2A6 isoenzyme. Additive effect with other systemic or topical photosensitising agents (e.g. anthralin, coal tar, nalidixic acid).

• Patient with idiosyncratic reactions to psoralen compounds
• Patient possessing light sensitive disease including lupus erythematosus, porphyria, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum and albinism
• Patient with melanoma or possessing a history of melanoma
• Patient with invasive squamous cell carcinomas
• Patient with aphakia

The most commonly reported side effect of Methoxsalen alone is nausea, which occurs with approximately 10% of all patients. This effect may be minimized or avoided by instructing the patient to take Methoxsalen with milk or food, or to divide the dose into two portions, taken approximately one-half hour apart. Other effects include nervousness, insomnia and psychological depression.

Pregnancy Category C. Methoxsalen should be given to a woman only if clearly needed. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Methoxsalen is administered to a nursing woman.

Skin burning: Serious burns from either UVA or sunlight (even through window glass) can result if the recommended dosage of the drug and/or exposure schedules are not maintained.

Carcinogenicity: The increasing risk of carcinoma appears great among patients who are fair skinned or had pre PUVA exposure or prolong treatment with tar UVB, ionizing radiation or arsenic.

Cataractogenicity: Among patients using proper eye protection, there is no evidence for a significantly increased risk of cataracts in association with PUVA therapy.

Patients must not sunbathe during the 24 hours prior to Methoxsalen ingestion and UV exposure.

Pediatric use: Safety in children has not been established.

In the event of Methoxsalen overdosage, induce emesis and keep the patient in a darkened room for at least 24 hours. Emesis is beneficial only within the first 2 to 3 hours after ingestion of Methoxsalen, since maximum blood levels are reached by this time.

Methoxsalen preparation

Store at 25°C; excursions permitted to 15°C-30°C.