Methoxsalen (oral)

Methoxsalen (oral)
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shanshan Cen, M.D. [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

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 vitiligo and who have special training and experience in photochemotherapy. 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. When methoxsalen is used in combination with photopheresis, refer to the UVAR* System Operator's Manual for specific warnings, cautions, indications, and instructions related to photopheresis. CAUTION: 8-MOP® Capsules (Methoxsalen Hard Gelatin Capsules) may not be interchanged with Oxsoralen-Ultra® Capsules (Methoxsalen Soft Gelatin Capsules) without retitration of the patient.

Overview

Methoxsalen (oral) is a naturally occurring photoactive substance that is FDA approved for the treatment of severe, recalcitrant, disabling psoriasis not adequately responsive to other forms of therapy and when the diagnosis has been supported by biopsy. It should be used with long wave ultraviolet radiation. There is a Black Box Warning for this drug as shown here. Common adverse reactions include erythema, pain of skin, pruritus, nausea, dizziness, headache, fatigue.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

A. Photochemotherapy (methoxsalen with long wave UVA radiation) is 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. Photochemotherapy is intended to be administered only in conjunction with a schedule of controlled doses of long wave ultraviolet radiation.

B. Photochemotherapy (methoxsalen with long wave ultraviolet radiation) is indicated for the repigmentation of idiopathic vitiligo.

C. Photopheresis (methoxsalen with long wave ultraviolet radiation of white blood cells) is indicated for use with the UVAR* System in the palliative treatment of the skin manifestations of cutaneous T-cell lymphoma (CTCL) in persons who have not been responsive to other forms of treatment. While this dosage form of methoxsalen has been approved for use in combination with photopheresis. Oxsoralen Ultra® Capsules have not been approved for that use.

Dosage

A. VITILIGO THERAPY 1. DRUG DOSAGE:

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

2. LIGHT EXPOSURE:

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

This image is provided by the National Library of Medicine.

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.

B. PSORIASIS THERAPY 1. DRUG DOSAGE - INITIAL THERAPY:

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

File:Methox ortal2.png

This image is provided by the National Library of Medicine.

Additional drug dosage directions are as follows:

a. Weight Change: In the event that the weight of a patient changes during treatment such that he/she falls into an adjacent weight range/dose category, no change in the dose of methoxsalen is usually required. If, in the physician's opinion, however, a weight change is sufficiently great to modify the drug dose, then an adjustment in the time of exposure to UVA should be made.

b. Dose/Week: The number of doses per week of methoxsalen capsules will be determined by the patient's schedule of UVA exposures. In no case should treatments be given more often than once every other day because the full extent of phototoxic reactions may not be evident until 48 hours after each exposure.

c. Dosage Increase: Dosage may be increased by 10 mg. after the fifteenth treatment under the conditions outlined in section XI.B.4.b.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methoxsalen (oral) in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methoxsalen (oral) in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Methoxsalen (oral) in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methoxsalen (oral) in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methoxsalen (oral) in pediatric patients.

Contraindications

A. Patients exhibiting idiosyncratic reactions to psoralen compounds.

B. Patients possessing a specific history of light sensitive disease states should not initiate methoxsalen therapy. Diseases associated with photosensitivity include lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum, and albinism.

C. Patients exhibiting melanoma or possessing a history of melanoma.

D. Patients exhibiting invasive squamous cell carcinomas.

E. 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 vitiligo and who have special training and experience in photochemotherapy. 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. When methoxsalen is used in combination with photopheresis, refer to the UVAR* System Operator's Manual for specific warnings, cautions, indications, and instructions related to photopheresis. CAUTION: 8-MOP® Capsules (Methoxsalen Hard Gelatin Capsules) may not be interchanged with Oxsoralen-Ultra® Capsules (Methoxsalen Soft Gelatin Capsules) without retitration of the patient.

A. 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.

B. CARCINOGENICITY

1. ANIMAL STUDIES

Topical or intraperitoneal methoxsalen has been reported to be a potent photocarcinogen in albino mice and hairless mice. However, methoxsalen given by the oral route to albino mice or by any route in pigmented mice is considerably less phototoxic or carcinogenic (Hakim et at. 196011; Pathak et al. 195912).

2. HUMAN STUDIES

A prospective study of 1380 patients over 5 years revealed an approximately nine-fold increase in risks of squamous cell carcinoma among PUVA treated patients (Stern et al. 197913 and Stern et al. 198014). This increase in risk appears greatest among patients who are fair skinned or had pre-PUVA exposure to 1) prolonged tar and UVB treatment, 2) ionizing radiation, or 3) arsenic.

In addition, an approximately two-fold increase in the risk of basal cell carcinoma was noted in this study. Roenigk et al. 198015 studied 690 patients for up to 4 years and found no increase in the risk of non-melanoma skin cancer. However, patients in this cohort had significantly less exposure to PUVA than in the Stern et al study. Recent analysis of new data in the Stern et al cohort (Stern et al., 199716) has shown that these patients had an elevated relative risk of contracting melanoma. The relative risk for melanoma in these patients was 2.3 (95 percent confidence interval 1.1 to 4.1). The risk is particularly higher in those patients who have received more than 250 PUVA treatments and in those whose treatment has spanned greater than 15 years earlier. Some patients developing melanoma did so even after having ceased PUVA therapy over 5 years earlier. These observations indicate the need for monitoring of PUVA patients for skin tumors throughout their lives.

In a study in Indian patients treated for 4 years for vitiligo, 12 percent developed keratoses, but not cancer, in the depigmented, vitiliginous areas (Mosher, 198017). Clinically, the keratoses were keratotic papules, actinic keratosis-like macules, nonscaling dome-shaped papules, and lichenoid porokeratotic-like papules.

C. CATARACTOGENICITY

1. ANIMAL STUDIES

Exposure to large doses of UVA causes cataracts in animals, and this effect is enhanced by the administration of methoxsalen (Cloud et al. 196018; Cloud et al. 196119; Freeman et al. 196920).

2. HUMAN STUDIES

It has been found that the concentration of methoxsalen in the lens is proportional to the serum level. If the lens is exposed to UVA during the time methoxsalen is present in the lens, photochemical action may lead to irreversible binding of methoxsalen to proteins and the DNA components of the lens (Lerman et al. 198021). However, if the lens is shielded from UVA, the methoxsalen will diffuse out of the lens in a 24 hour period21. Patients should be told emphatically to wear UVA-absorbing, wraparound sunglasses for the twenty-four (24) hour period following ingestion of methoxsalen, whether exposed to direct or indirect sunlight in the open or through a window glass.

Among patients using proper eye protection, there is no evidence for a significantly increased risk of cataracts in association with PUVA therapy.13 Thirty-five of 1380 patients have developed cataracts in the five years since their first PUVA treatment. This incidence is comparable to that expected in a population of this size and age distribution. No relationship between PUVA dose and cataract risk in this group has been noted.

D. ACTINIC DEGENERATION

Exposure to sunlight and/or ultraviolet radiation may result in "premature aging" of the skin.

E. BASAL CELL CARCINOMAS

Patients exhibiting multiple basal cell carcinomas or having a history of basal cell carcinomas should be diligently observed and treated.

F. RADIATION THERAPY

Patients having a history of previous x-ray therapy or grenz ray therapy should be diligently observed for signs of carcinoma.

G. ARSENIC THERAPY

Patients having a history of previous arsenic therapy should be diligently observed for signs of carcinoma.

H. HEPATIC DISEASES

Patients with hepatic insufficiency should be treated with caution since hepatic biotransformation is necessary for drug urinary excretion.

I. CARDIAC DISEASES

Patients with cardiac diseases or others who may be unable to tolerate prolonged standing or exposure to heat stress should not be treated in a vertical UVA chamber.

J. TOTAL DOSAGE

The total cumulative dose of UVA that can be given over long periods of time with safety has not as yet been established.

K. 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, fluoroquinolone antibiotics, halogenated salicylanilides (bacteriostatic soaps), sulfonamides, tetracyclines, thiazides, and certain organic staining dyes such as methylene blue, toluidine blue, rose bengal, and mythyl orange.

Adverse Reactions

Clinical Trials Experience

A. METHOXSALEN:

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.

B. COMBINED METHOXSALEN/UVA THERAPY:

1. PRURITUS:

This adverse reaction occurs with approximately 10% of all patients. In most cases, pruritus can be alleviated with frequent application of bland emollients or other topical agents; severe pruritus may require systemic treatment. If pruritus is unresponsive to these measures, shield pruritic areas from further UVA exposure until the condition resolves. If intractable pruritus is generalized, UVA treatment should be discontinued until the pruritus disappears.

2. ERYTHEMA:

Mild, transient erythema at 24-48 hours after PUVA therapy is an expected reaction and indicates that a therapeutic interaction between methoxsalen and UVA occurred. An area showing moderate erythema (greater than Grade 2 – See TABLE 1 for grades of erythema) should be shielded during subsequent UVA exposures until the erythema has resolved. Erythema greater than Grade 2 which appears within 24 hours after UVA treatment may signal a potentially severe burn. Erythema may become progressively worse over the next 24 hours, since the peak erythemal reaction characteristically occurs 48 hours or later after methoxsalen ingestion. The patient should be protected from further UVA exposures and sunlight, and should be monitored closely.

3. IMPORTANT DIFFERENCES BETWEEN PUVA ERYTHEMA AND SUNBURN:

PUVA-induced inflammation differs from sunburn or UVB phototherapy in several ways. The in situ depth of photochemistry is deeper within the tissue because UVA is transmitted further into the skin. The DNA lesions induced by PUVA are very different from UV-induced thymine dimers and may lead to a DNA crosslink. This DNA lesion may be more problematic to the cell because crosslinks are more lethal and psoralen-DNA photoproducts may be "new" or unfamiliar substrates for DNA repair enzymes. DNA synthesis is also suppressed longer after PUVA. The time course of delayed erythema is different with PUVA and may not involve the usual mediators seen in sunburn. PUVA-induced redness may be just beginning at 24 hours, when UVB erythema has already passed its peak. The erythema dose-response curve is also steeper for PUVA. Compared to equally erythemogenic doses of UVB, the histologic alterations induced by PUVA show more dermal vessel damage and longer duration of epidermal and dermal abnormalities.

4. OTHER ADVERSE REACTIONS:

Those reported include edema, dizziness, headache, malaise, depression, hypopigmentation, vesiculation and bullae formation, non-specific rash, herpes simplex, miliaria, urticaria, folliculitis, gastrointestinal disturbances, cutaneous tenderness, leg cramps, hypotension, and extension of psoriasis.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Methoxsalen (oral) in the drug label.

Drug Interactions

See WARNINGS Section.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C Animal reproduction studies have not been conducted with methoxsalen. It is also not known whether methoxsalen can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Methoxsalen should be given to a woman only if clearly needed.
Pregnancy Category (AUS): B2 There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Methoxsalen (oral) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Methoxsalen (oral) during labor and delivery.

Nursing Mothers

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.

Pediatric Use

Safety in children has not been established.

Geriatic Use

There is no FDA guidance on the use of Methoxsalen (oral) with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Methoxsalen (oral) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Methoxsalen (oral) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Methoxsalen (oral) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Methoxsalen (oral) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Methoxsalen (oral) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Methoxsalen (oral) in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

Monitoring

There is limited information regarding Monitoring of Methoxsalen (oral) in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Methoxsalen (oral) in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Methoxsalen (oral) in the drug label.

Pharmacology

There is limited information regarding Methoxsalen (oral) Pharmacology in the drug label.

Mechanism of Action

Structure

File:Methoxsalen (oral)01.png

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Methoxsalen (oral) in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Methoxsalen (oral) in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Methoxsalen (oral) in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Methoxsalen (oral) in the drug label.

How Supplied

Storage

There is limited information regarding Methoxsalen (oral) Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Methoxsalen (oral) |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Methoxsalen (oral) |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Methoxsalen (oral) in the drug label.

Precautions with Alcohol

• Alcohol-Methoxsalen (oral) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• OXSORALEN-ULTRA®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.