Data from FDA - Curated by Toby Galbraith - Last updated 11 January 2017

Licensing authority

FDA (Food and Drug Administration, USA)

Indication(s)

III. INDICATIONS AND USAGE 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.

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Advisory information

contraindications

IV. 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.

Special warnings and precautions

VI. PRECAUTIONS A. GENERAL - APPLICABLE TO BOTH VITILIGO AND PSORIASIS TREATMENT: 1.

BEFORE METHOXSALEN INGESTION Patients must not sunbathe during the 24 hours prior to methoxsalen ingestion and UV exposure.

The presence of a sunburn may prevent an accurate evaluation of the patient 's response to photochemotherapy.

2.

AFTER METHOXSALEN INGESTION a. UVA-absorbing wrap-around sunglasses should be worn during daylight for 24 hours after methoxsalen ingestion.

The protective eyewear must be designed to prevent entry of stray radiation to the eyes, including that which may enter from the sides of the eyewear.

The protective eyewear is used to prevent the irreversible binding of methoxsalen to the proteins and DNA components of the lens.

Cataracts form when enough of the binding occurs.

Visual discrimination should be permitted by the eyewear for patient well-being and comfort.

b. Patients must avoid sun exposure, even through window glass or cloud cover, for at least 8 hours after methoxsalen ingestion.

If sun exposure can not be avoided, the patient should wear protective devices such as a hat and gloves, and/or apply sunscreens which contain ingredients that filter out UVA radiation (e.g., sunscreens containing benzophenone and/or PABA esters which exhibit a sun protective factor equal to or greater than 15).

These chemical sunscreens should be applied to all areas that might be exposed to the sun (including lips).

Sunscreens should not be applied to areas affected by psoriasis until after the patient has been treated in the UVA chamber.

3.

DURING PUVA THERAPY a. Total UVA-absorbing/blocking goggles mechanically designed to give maximal ocular protection must be worn.

Failure to do so may increase the risk of cataract formation.

A reliable radiometer can be used to verify elimination of UVA transmission through the goggles.

b. Abdominal skin, breasts, genitalia, and other sensitive areas should be protected for approximately 1/3 of the initial exposure time until tanning occurs.

c. Unless affected by disease, male genitalia should be shielded.

4.

AFTER COMBINED METHOXSALEN/UVA THERAPY a. UVA-absorbing wrap-around sunglasses should be worn during the daylight for 24 hours after combined methoxsalen/UVA therapy.

b. Patients should not sunbathe for 48 hours after therapy.

Erythema and/or burning due to photochemotherapy and sunburn due to sun exposure are additive.

5.

VITILIGO THERAPY a.

The dosage of methoxsalen should not be increased above 0.6 mg/kg since overdosage may result in serious burning of the skin.

b. Eye and skin sun protection as described in the Precautions - General section should be observed.

B. INFORMATION FOR PATIENTS: See accompanying Patient Package Insert.

C. LABORATORY TESTS: 1.

Patients should have an ophthalmologic examination prior to the start of therapy, and thence yearly.

2.

Patients should have the following tests prior to the start of therapy and should be retested 6-12 months subsequently.

Additional tests at more extended time periods should be conducted as clinically indicated.

a. Complete Blood Count (Hemoglobin or Hematocrit; White Blood Count - if abnormal, a differential count).

b. Anti-nuclear Antibodies.

c. Liver Function Tests.

d. Renal Function Tests (Creatinine or Blood Urea Nitrogen).

D. DRUG INTERACTIONS: See Warnings Section.

E. CARCINOGENESIS: See Warnings Section.

F. PREGNANCY: Pregnancy Category 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.

G. 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.

H. PEDIATRIC USE: Safety in children has not been established.

Potential hazards of long-term therapy include the possibilities of carcinogenicity and cataractogenicity as described in the Warnings Section as well as the probability of actinic degeneration which is also described in the Warnings Section.

Adverse reactions

VII. ADVERSE REACTIONS 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.

Any 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.

Usage information

Dosing and administration

IX. DRUG DOSAGE & ADMINISTRATION 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: Basic Skin Color Light Medium Dark Initial Exposure 15 min. 20 min. 25 min.

Second Exposure 20 min. 25 min. 30 min.

Third Exposure 25 min. 30 min. 35 min.

Fourth Exposure 30 min. 35 min. 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.

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: Patient 's Weight Dose (kg) (lbs) (mg) <30 <66 10 30-50 66-110 20 51-65 112-143 30 66-80 146-176 40 81-90 179-198 50 91-115 201-254 60 >115 >254 70

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.

Pregnancy and lactation
G. 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.

Interactions

D. DRUG INTERACTIONS: See Warnings Section.

More information

Category Value
Authorisation number NDA009048
Agency product number U4VJ29L7BQ
Orphan designation No
Product NDC 0187-0651
Date Last Revised 01-09-2013
Type HUMAN PRESCRIPTION DRUG
RXCUI 207073
Storage and handling Store at 25°C (77°F); excursions permitted to 15°C- 30°C (59°F- 86°F).
Marketing authorisation holder Valeant Pharmaceuticals North America LLC
Warnings

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.