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Black Box Warning
WARNING
See full prescribing information for complete Boxed Warning.
Methoxsalen with UV radiation should be used only by physicians who have special competence in the diagnosis and treatment of psoriasis and who have special training and experience in photochemotherapy. The use of Psoralen and ultraviolet radiation therapy should be under constant supervision of such a physician. For the treatment of patients with psoriasis, photochemotherapy should be restricted to patients with severe, recalcitrant, disabling psoriasis which is not adequately responsive to other forms of therapy, and only when the diagnosis is certain. Because of the possibilities of ocular damage, aging of the skin, and skin cancer (including melanoma), the patient should be fully informed by the physician of the risks inherent in this therapy.
Methoxsalen Capsules, USP should not be used interchangeably with regular Oxsoralen® or 8-MOP® (Methoxsalen Hard Gelatin Capsules). This new dosage form of methoxsalen exhibits significantly greater bioavailability and earlier photosensitization onset time than previous methoxsalen dosage forms. Patients should be treated in accordance with the dosimetry specifically recommended for this product. The minimum phototoxic dose (MPD) and phototoxic peak time after drug administration prior to onset of photochemotherapy with this dosage form should be determined.
Overview
Methoxsalen (topical) is an antipsoriatic that is FDA approved for the {{{indicationType}}} of vitiligo. There is a Black Box Warning for this drug as shown here. Common adverse reactions include erythema, pain of skin, pruritus, nausea, dizziness, headache, and fatigue.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Vitiligo
As a topical repigmenting agent in vitiligo in conjunction with controlled doses of ultraviolet A (320-400 nm) or sunlight.
OXSORALEN Lotion is applied to a well-defined area of vitiligo by the physician and the area is then exposed to a suitable source 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.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Methoxsalen (topical) in adult patients.
Non–Guideline-Supported Use
Mycosis fungoides
. Methoxsalen was given in doses of 0.65 milligram/kilogram orally 2 to 3 hours prior to irradiation with UVA (0.1 to 0.5 Joules/cm(2).[1]
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Methoxsalen (topical) in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Methoxsalen (topical) in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Methoxsalen (topical) in pediatric patients.
Contraindications
Patients exhibiting idiosyncratic reactions to psoralen compounds.
Patients with aphakia, because of the significantly increased risk of retinal damage due to the absence of lenses.
Warnings
WARNING
See full prescribing information for complete Boxed Warning.
Methoxsalen with UV radiation should be used only by physicians who have special competence in the diagnosis and treatment of psoriasis and who have special training and experience in photochemotherapy. The use of Psoralen and ultraviolet radiation therapy should be under constant supervision of such a physician. For the treatment of patients with psoriasis, photochemotherapy should be restricted to patients with severe, recalcitrant, disabling psoriasis which is not adequately responsive to other forms of therapy, and only when the diagnosis is certain. Because of the possibilities of ocular damage, aging of the skin, and skin cancer (including melanoma), the patient should be fully informed by the physician of the risks inherent in this therapy.
Methoxsalen Capsules, USP should not be used interchangeably with regular Oxsoralen® or 8-MOP® (Methoxsalen Hard Gelatin Capsules). This new dosage form of methoxsalen exhibits significantly greater bioavailability and earlier photosensitization onset time than previous methoxsalen dosage forms. Patients should be treated in accordance with the dosimetry specifically recommended for this product. The minimum phototoxic dose (MPD) and phototoxic peak time after drug administration prior to onset of photochemotherapy with this dosage form should be determined.
Skin Burns
Serious skin burns from either UVA or sunlight (even through window glass) can result if recommended exposure schedule is exceeded and/or protective covering or sunscreens are not used. The blistering of the skin sometimes encountered after UV exposure generally heals without complication or scarring. (Farrington Daniels, Jr., M.D., personal communication). Suitable covering of the area of application or a topical sunblock should follow the therapeutic UVA exposure.
Carcinogenicity
Animal Studies. Topical methoxsalen has been reported to be a potent photocarcinogen in certain strains of mice. (Pathak et al 1959) 5.
Human Studies. None of our clinical investigators reported skin cancer as a complication of topical treatment for vitiligo. However, it is recommended that caution be exercised when the patient is fair-skinned, has a history of prior coal tar UV treatment, or has had ionizing radiation or taken arsenical compounds. Such patients who subsequently have oral psoralen – UVA treatment (PUVA) are at increased risk for developing skin cancer.
Concomitant Therapy
Special care should be exercised in treating patients who are receiving concomitant therapy (either topically or systemically) with known photosensitizing agents such as anthralin, coal tar or coal tar derivatives, griseofulvin, phenothiazines, nalidixic acid, halogenated salicylanilides (bacteriostatic soaps), sulfonamides, tetracyclines, thiazides and certain organic staining dyes such as methylene blue, toluidine blue, rose bengal, and methyl orange.
Precautions
A. This product should be applied only in small well-defined lesions and preferably on lesions which can be protected by clothing or a sunscreen from subsequent exposure to radiant UVA. If this product is used to treat vitiligo of face or hands, be very emphatic when instructing patient to keep the treated areas protected from light by use of protective clothing or sunscreening agents. The area of application may be highly photosensitive for several days and may result in severe burn injury if exposed to additional UV or sunlight.
Adverse Reactions
Clinical Trials Experience
Systemic adverse reactions have not been reported. The most common adverse reaction is severe burns of the treated area from overexposure to UVA, including sunlight. TREATMENT MUST BE INDIVIDUALIZED. Minor blistering of the skin is not a contraindication to further treatment and generally heals without incident. Treatment would be the standard for burn therapy. Since 1953, many studies have demonstrated the safety and effectiveness of topical methoxsalen and UVA for the treatment of vitiligo when used as directed.
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Methoxsalen (topical) in the drug label.
Drug Interactions
There is limited information regarding Methoxsalen (topical) Drug Interactions in the drug label.
Animal reproduction studies have not been conducted with topical methoxsalen. It is also not known whether methoxsalen can cause fetal harm when used topically on a pregnant woman or affect reproductive capacity. It is not known to what degree, if any, topical methoxsalen is absorbed systemically. Topical methoxsalen should be used in women only when clearly indicated.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Methoxsalen (topical) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Methoxsalen (topical) during labor and delivery.
Nursing Mothers
It is not known whether topical methoxsalen is absorbed or excreted in human milk. Caution is advised when topical methoxsalen is used in a nursing mother.
Pediatric Use
Safety and effectiveness in children below the age of 12 years have not been established.
Geriatic Use
There is no FDA guidance on the use of Methoxsalen (topical) with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Methoxsalen (topical) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Methoxsalen (topical) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Methoxsalen (topical) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Methoxsalen (topical) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Methoxsalen (topical) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Methoxsalen (topical) in patients who are immunocompromised.
Administration and Monitoring
Administration
Topical
Monitoring
There is limited information regarding Monitoring of Methoxsalen (topical) in the drug label.
IV Compatibility
There is limited information regarding IV Compatibility of Methoxsalen (topical) in the drug label.
Overdosage
Acute Overdose
This does not apply to topical usage. In the unlikely event that the lotion is ingested, standard procedures for poisoning should be followed, including gastric lavage. Protection from UVA or daylight for hours or days would also be necessary. The patient should be kept in a darkened room.
Chronic Overdose
There is limited information regarding Chronic Overdose of Methoxsalen (topical) in the drug label.
The mechanisms of therapy are not known. In the treatment of psoriasis, the mechanism is most often assumed to be DNA photodamage and resulting decrease in cell proliferation but other vascular, leukocyte, or cell regulatory mechanisms may also be playing some role. Psoriasis is a hyper-proliferative disorder and other agents known to be therapeutic for psoriasis are known to inhibit DNA synthesis.
Structure
Methoxsalen Capsules, USP contain 10 mg. methoxsalen (8-methoxsalen). Methoxsalen occurs as white to pale yellow crystals and can be obtained naturally from seeds of Ammi majus and roots of Heracleum Candicans or through synthesis. Methoxsalen is practically insoluble in water, freely soluble in chloroform, soluble in boiling alcohol, in acetone, in acetic acid, in propylene glycol, and in benzene, sparingly soluble in boiling water and in ether. The chemical name of methoxsalen is 9-methoxy-7H-furo [3,2-g] [1] benzopyran-7-one; its empirical formula is C12H8O4 and the molecular weight is 216.19. The structural formula is:
Methoxsalen Capsules, USP are available as soft gelatin capsules containing the following inactive ingredients: polyethylene glycol 400, sorbital special, gelatin, glycerin, water, titanium dioxide, methyl & propylparaben, D&C yellow 10, FD&C blue 1, FD&C yellow 6.
Pharmacodynamics
There is limited information regarding Pharmacodynamics of Methoxsalen (topical) in the drug label.
Pharmacokinetics
The combination treatment regimen of psoralen (P) and ultraviolet radiation of 320-400 nm wavelength commonly referred to as UVA is known by the acronym, PUVA. Skin reactivity to UVA (320-400 nm) radiation is markedly enhanced by the ingestion of methoxsalen. In a well controlled bioavailability study, Methoxsalen Capsules, USP reached peak drug levels in the blood of test subjects between 0.5 and 4 hours (Mean = 1.8 hours) as compared to between 1.5 and 6 hours (Mean = 3.0 hours) for regular Oxsoralen when administered with 8 ounces of milk. Peak drug levels were 2 to 3 fold greater when the overall extent of drug absorption was approximately two fold greater for Methoxsalen Capsules, USP as compared to regular Oxsoralen Capsules. Detectable methoxsalen levels were observed up to 12 hours post dose. The drug half-life is approximately 2 hours. Photosensitivity studies demonstrate a shorter time of peak photosensitivity of 1.5 to 2.1 hours vs. 3.9 to 4.25 hours for regular Oxsoralen capsules. In addition, the mean minimal erythema dose (MED), J/cm2, for the Methoxsalen Capsules, USP is substantially less than that required for regular Oxsoralen Capsules.
Methoxsalen is reversibly bound to serum albumin and is also preferentially taken up by epidermal cells. At a dose which is six times larger than that used in humans, it induces mixed function oxidases in the liver of mice. 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 which leads to the formation of both monofunctional (addition to a single strand of DNA) and bifunctional (crosslinking of psoralen to both strands of DNA) adducts. Reactions with proteins have also been described.
Methoxsalen acts as a photosensitizer. Administration of the drug and subsequent exposure to UVA can lead to cell injury. Orally administered methoxsalen reaches the skin via the blood and UVA penetrates well into the skin. If sufficient cell injury occurs in the skin, an inflammatory reaction occurs. The most obvious manifestation of this reaction is delayed erythema, which may not begin for several hours and peaks at 48-72 hours. The inflammation is followed, over several days to weeks, by repair which is manifested by increased melanization of the epidermis and thickening of the stratum corneum.
Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Methoxsalen (topical) in the drug label.
Clinical Studies
There is limited information regarding Clinical Studies of Methoxsalen (topical) in the drug label.
How Supplied
Oxsoralen Lotion containing 1% methoxsalen (8-methoxypsoralen) packaged in 1 ounce (29.57 ml) amber glass bottles (NDC 0187-0402-31). Store at 25°C (77°F); excursion permitted to 15°C-30°C (59°F-86°F).
Storage
There is limited information regarding Methoxsalen (topical) Storage in the drug label.
Images
Drug Images
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