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

Skin Preparation

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.

Topical- Adult use: Repigmentation of vitiliginous areas: As 1% soln (diluted to 0.1-0.01%): Apply over lesions then expose to UVA immediately after application or wait up to 2 hr. Protect the area surrounding the lesion with a sunscreen. Wash and protect lesions from light after treatment; protection may be up to ?48 hr. Treatment is usually repeated once wkly. Substantial repigmentation usually requires 6-9 mth of treatment. Psoriasis: As a 0.15% soln (diluted to 0.015%, if necessary): Apply to affected areas 15 min before UVA exposure. Alternatively, patient may take a whole body bath in methoxsalen soln for 15 min followed by immediate UVA exposure. For treating affected areas, immerse the affected areas for 15 min into 3 mg/L soln of hand and foot soaks followed by a 30-min delay before UVA exposure. Baths or soaks are given twice wkly. Geriatric use: Refer to adult dosing. Pediatric use (Children ?12 years): Vitiligo: Refer to adult dosing. Oral (Adult)- Repigmentation of vitiliginous areas: 20 mg or up to 600 mcg/kg 2-4 hr before measured periods of UVA exposure depending on the preparation, given twice wkly or on alternate days, with at least 48-hr intervals. Psoriasis: Up to approx 600 mcg/kg, given 1.5-3 hr before UVA exposure, depending on the preparation. Treatment is usually given twice wkly or increased as necessary, with at least 48-hr intervals between doses. If there is no or minimal response after the 15th PUVA treatment, dose may be increased by 10 mg and this dose used for the remainder of the treatment course.

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 l Patient possessing light sensitive disease including lupus erythematosus, porphyria, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum and albinism l Patient with melanoma or possessing a history of melanoma l Patient with invasive squamous cell carcinomas l 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.

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.

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