Trisoralen (Trisoralen)

TRISORALEN™ ICN Trioxsalen Melanizing Agent

Action And Clinical Pharmacology: Trioxsalen is a synthetic melanizing agent structurally and pharmacologically related to methoxsalen. The normal pigmentation of the skin is due to melanin, which is produced in the cytoplasm of the melanocytes located in the basal layers of the epidermis at its junction with the dermis. Melanin is formed by the oxidation of tyrosine to DOPA (dihydroxyphenylalanine) with tyrosinase as catalyst. This enzymatic reaction, however, must be activated by radiant energy in the form of ultraviolet (UV) light, preferably between 2 900 and 3 800 angstroms (black light).

The exact mechanism of the action of psoralens in the process of melanogenesis is not known. One group of investigators feels that the psoralens have a specific effect on the epidermis or, more specifically, on the melanocytes. Another group feels that the primary response to the psoralens is an inflammatory one and that the process of melanogenesis is secondary.

Indications And Clinical Uses: Taken approximately 2 hours before measured periods of exposure to UV light, trioxsalen facilitates:

Repigmentation of idiopathic vitiligo: Repigmentation, not equally reversible in every patient, will vary in completeness, time of onset, and duration. The rate of completeness of pigmentation with respect to locations of lesions, occurs more rapidly on fleshy regions, such as the face, abdomen, and buttocks, and less rapidly over bony areas such as the dorsum of the hands and feet. Repigmentation may begin after a few weeks; however, significant results may take as long as 6 to 9 months, and repigmentation, at the optimum level, may, in some cases, require maintenance dosage to retain the new pigment. If follicular repigmentation is not apparent after 3 months of daily treatment, treatment should be discontinued as a failure.

Increasing tolerance to sunlight: In blond persons and those with fair complexions who suffer painful reactions when exposed to sunlight, trioxsalen aids in increasing resistance to solar damage. Certain persons who are allergic to sunlight or exhibit sun sensitivity may be benefited by trioxsalen’s protective action.

In albinism, trioxsalen will increase the tolerance of the skin to sunlight, although no pigment is formed. This protective action seems to be related to the thickening of the horny layer and retention of melanin which produces a thickened, melanized stratum corneum and formation of a stratum lucidum.

Contra-Indications: Diseases associated with photosensitivity such as porphyria, acute lupus erythematosus or leukoderma of infectious origin. Safety for use in children 12 years and under has not been established. Do not use photosensitizing preparations, internal or external, concomitantly with trioxsalen.

Precautions: Trioxsalen is a potent drug. Dosage and exposure time should not be increased. Overdosage and/or overexposure may result in serious burning and blistering. When used to increase tolerance to sunlight, the total trioxsalen dosage should not exceed 28 tablets (140 mg), taken in daily single 10 mg doses on a continuous or interrupted regimen. To prevent harmful effects, the patient must be carefully instructed to adhere to the prescribed dosage schedule and procedure.

Pregnancy: Safe use in human pregnancy has not been established, although animal reproduction studies (mice, rats) demonstrated no teratogenic effect. Therefore, use trioxsalen during pregnancy only when the probable benefits outweigh the possible risks.

Although there are no clinical reports or tests to verify that more severe reactions may result from the concomitant ingestion of food containing furocoumarin while on trioxsalen therapy, the patient should be warned that eating limes, figs, parsley, parsnips, mustard, carrots and celery, might be dangerous. Use trioxsalen with caution in patients with defective coagulation or in patients receiving anticoagulants.

Sunglasses should be worn during exposure and the lips protected with a light-screening lipstick. Initiate sunlamp exposure according to the sunlamp manufacturer’s directions.

Adverse Reactions: Severe burns can result from excessive sunlight or sunlamp UV exposure. Occasionally, gastric discomfort may occur, which can be minimized by taking the medication with milk or after a meal. Some patients who cannot tolerate 10 mg will tolerate 5 mg. This dosage produces the same therapeutic effect but more slowly. In a small percentage of cases, abnormal liver function tests have been reported, as measured by increased thymol turbidity (Thymol Turbidity Test); by increased BSP retention; or by elevated values following the Ceph-Floc test (Cephalin-Cholesterol Flocculation Test).

Symptoms And Treatment Of Overdose: Symptoms and Treatment: If an overdose of trioxsalen or UV light has been taken, encourage emesis. Keep the individual in a darkened room for 8 hours or until cutaneous reactions subside. The treatment for severe reactions resulting from overdosage or overexposure should follow accepted procedures for treatment of severe burns.

Dosage And Administration: Adults and children over 12 years: Vitiligo: 10 mg 2 to 4 hours before measured periods of UV exposure or fluorescent black light. See suggested sun exposure guide.

To ensure tolerance to sunlight: 10 mg daily 2 hours before measured periods of exposure to sun or UV irradiation. Not to be continued for longer than 14 days. The dosage should not be increased, as severe burning may occur. See suggested sun exposure guide.

Subsequent Exposure: Gradually increase exposure based on erythema and tenderness.

Supplied: Each white, round, sugar-coated tablet, printed ICN on one side and 303 on the other side contains: trioxsalen USP 5 mg. Nonmedicinal ingredients: lactose, magnesium stearate, starch, sucrose and talc. Bottles of 100.

TRISORALEN™ ICN Trioxsalen Melanizing Agent