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Methoxsalen (Topical)


VA CLASSIFICATION
Primary: DE900
Secondary: DE802

Commonly used brand name(s): Oxsoralen Lotion; UltraMOP Lotion.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Repigmenting agent (topical)—

hair growth stimulant, alopecia areata (topical){07}

antipsoriatic (topical)—
Note: Methoxsalen is used in conjunction with ultraviolet light A (UVA). {04} This mode of treatment is known as PUVA (psoralen plus ultraviolet light A).



Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Vitiligo (treatment)—PUVA is indicated for repigmentation in the treatment of vitiligo. {03} {08} It is not effective in producing pigmentation in leukoderma of infectious origin or in albinism.

[Skin, increased tolerance to sunlight]1—PUVA has been used to increase skin tolerance to sunlight. {08}

[Psoriasis (treatment)]{08}{11}{12}—PUVA has been used in the treatment of severe psoriasis that has not responded to other therapy.

[Mycosis fungoides (treatment)]1—PUVA is used in the treatment of mycosis fungoides. {13}

[Alopecia areata (treatment)]1{07}
[Dermatoses, inflammatory (treatment)]1{07}
[Eczema (treatment)]1or{07}
[Lichen planus (treatment)]1{07}—PUVA is used in the treatment of alopecia areata, inflammatory dermatoses, eczema, and lichen planus. {01}

Unaccepted
The unsupervised use of methoxsalen to promote tanning is dangerous and should be discouraged.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Psoralen derivative.
Molecular weight—
    216.19 {05}

Mechanism of action/Effect:

Exact mechanism of erythemogenic, melanogenic, and cytotoxic response in the epidermis is unknown, but may involve increased tyrosinase activity in melanin-producing cells, as well as inhibition of DNA synthesis, cell division, and epidermal turnover. Successful pigmentation requires the presence of functioning melanocytes.

Absorption:

Extent of systemic absorption is unknown.

Biotransformation:

Activated by long-wavelength UVA in the range of 320 to 400 (maximal effect at 365) nanometers (nm).

Onset of action:

Vitiligo—Up to 6 months.

For increased sensitivity of skin to sunlight—1 hour.

Tanning—Within a few days.

Time to peak effect:

Increased sensitivity of skin to sunlight—2 hours (peak erythematous response may not occur for 2 days).

Duration of action:

Increased sensitivity of skin to sunlight—Several days.


Precautions to Consider

Carcinogenicity

Psoralens have been found to augment UVA-induced carcinogenicity in laboratory animals. {02} In addition, studies in humans treated with systemic methoxsalen plus UVA have shown an increase in the risk of squamous cell carcinoma. {02} The possibility of increased risk may exist also for topical methoxsalen and systemic trioxsalen. This risk appears to be greatest in patients with predisposing risk factors, such as fair skin {02} or a hypersensitivity to sunlight; a history of skin cancer, {02} exposure to ionizing radiation, {02} or excessive exposure to sunlight; or a history of treatment with tar and UVB (prolonged), {02} arsenicals, {02} or topical nitrogen mustard. {07}

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans.

Studies have not been done in animals.

FDA Pregnancy Category C. {03}

Breast-feeding

It is not known whether topical methoxsalen is distributed into breast milk. {03} However, problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of topical methoxsalen have not been performed in children up to 12 years of age. Safety and efficacy have not been established. {03}


Geriatrics


Appropriate studies on the relationship of age to the effects of topical methoxsalen have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication. {08}

Furocoumarin-containing foods, such as limes, figs, parsley, parsnips, mustard, carrots, and celery    (although there have been no reports of serious reactions, caution and avoidance of these foods are recommended because of the risk of additive phototoxicity)


Photosensitizing medications, other    (concurrent use of methoxsalen with other photosensitizing medications, systemic or topical, may cause additive photosensitizing effects; concurrent use with coal tar or coal tar derivatives or with trioxsalen is not recommended)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Liver function tests    (Abnormal liver function tests have been reported, but the relationship to the medication is not clear)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Albinism or
» Hydroa or
» Leukoderma of infectious origin or
» Lupus erythematosus,{03} acute or
» Polymorphic light eruptions or
» Porphyria or{03}
» Xeroderma pigmentosum{03}    (these conditions are associated with photosensitization)


Cardiovascular disease, severe    (because of the potential {09} heat stress or the prolonged standing associated with {02} each UVA treatment, patients with severe cardiovascular disease should be carefully monitored and if possible {09} not be treated in a vertical UVA chamber {02})


Infection, chronic
Sensitivity to methoxsalen
» Skin cancer, history of{03}
Sunlight allergy, or family history of    (PUVA may cause photoallergic contact dermatitis or precipitate sunlight allergy)


» Caution should be used in evaluating for treatment and subsequently treating{09} patients with a history of having taken arsenicals{03} or having received x-rays,{03} cytotoxic therapy, or coal tar and ultraviolet light B (UVB) therapy{03} because of the increased risk of skin cancer.{02}{03}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Monitoring for melanoma and other skin carcinomas    (recommended in patients receiving methoxsalen for prolonged periods, since long-term safety has not been established)




Side/Adverse Effects

Note: There is an increased risk of skin cancer with systemic methoxsalen plus UVA. {03} {07} The possibility of increased risk may exist also with topical methoxsalen. {07} This risk appears to be greatest in patients with predisposing risk factors, such as fair skin or a hypersensitivity to sunlight; a history of skin cancer, exposure to ionizing radiation, or excessive exposure to sunlight; or a history of treatment with tar and UVB (prolonged), arsenicals, or topical nitrogen mustard. {07} {08}
Premature aging of the skin may occur as a result of prolonged treatment with systemic methoxsalen plus UVA. {07} The possibility of risk may exist also with topical methoxsalen. This effect is permanent and is similar to the results of excessive exposure to sunlight. {07}

The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Symptoms of overdose or overexposure to ultraviolet light
    
Blistering and peeling of skin
    
reddened, sore skin
    
swelling, especially in feet or lower legs





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
    
Blistering and peeling of skin
    
reddened, sore skin
    
swelling, especially in feet or lower legs


Treatment of overdose


To decrease absorption:
Inducing emesis. {03} {07}



Specific treatment:
For ingestion of topical methoxsalen solution: Keeping patient in a darkened room for at least 24 hours following methoxsalen ingestion to prevent the possibility of sun exposure and subsequent burn injury. {03} {07}

For overexposure to sunlight or ultraviolet light: Keeping patient in a darkened room for at least 24 hours following ingestion of methoxsalen to prevent the possibility of further sun exposure and subsequent burn injury {07} while assessment of the extent of damage is made. {03} With topical methoxsalen, erythema may not begin for several hours following overexposure and may not peak for 2 or 3 days or longer. {03}



Supportive care:
Treating patient symptomatically for burns, depending on their extent and severity. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Methoxsalen (Topical).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to methoxsalen



Carcinogenicity—
Possibility of increased risk of squamous cell carcinoma, especially in patients with predisposing risk factors such as fair skin and those with increased sensitivity to sunlight





Use in children—Not recommended for use in children up to 12 years of age

Diet—Avoiding eating furocoumarin-containing foods (limes, figs, parsley, parsnips, mustard, carrots, celery)
Other medical problems, especially acute lupus erythematosus; albinism; hydroa; leukoderma of infectious origin; polymorphic light eruptions; porphyria; xeroderma pigmentosum; history of skin cancer; history of having taken arsenicals; history of having received x-rays, cytotoxic therapy, or coal tar and ultraviolet light B (UVB) therapy

Proper use of this medication
Using medication only under the direct supervision of the physician

» Proper dosing

Precautions while using this medication
Importance of regular visits to physician for treatments and to have progress checked

» Protecting skin from sunlight, even through window glass or on a cloudy day, for at least 12 to 48 hours following treatment; washing treated areas after light treatment

Possibility of continued skin sensitivity to sunlight because of medication; using extra precautions for at least 72 hours following each treatment; not sunbathing anytime during course of treatment {09}

» Possibility of dry skin or itching; checking with physician before treating


Side/adverse effects
There is an increased risk of developing skin cancer when treated with systemic methoxsalen. {07} The possibility of increased risk may exist also with topical methoxsalen. {07} The treated areas should be examined regularly and the physician shown skin sores that do not heal, new skin growths, and skin growths that have changed in appearance or feel. {07}

Premature aging of the skin may occur as a result of prolonged treatment with systemic methoxsalen. {07} The possibility of risk may exist also with topical methoxsalen. {07} This effect is permanent and is similar to the results of excessive exposure to sunlight. {07}

Signs of potential side effects, especially symptoms of overdose or overexposure to ultraviolet light


General Dosing Information
Topical application should be performed only by {03} or under the direct supervision of a physician familiar with the use of PUVA therapy.

Topical application causes a greater and less predictable photosensitizing response than does oral administration.

It is recommended that methoxsalen be applied only to small, well-defined lesions (less than 10 square cm) and that it be removed from the skin following exposure to sunlight or ultraviolet light. {03}

Exposure to sunlight or ultraviolet light should be carefully controlled and adjusted on an individual basis according to skin type and tolerance. Exposure time to sunlight should be reduced at high altitudes or at midday.

Because topical application results in a higher concentration of methoxsalen in the epidermis than does oral administration, the dose of UVA is generally lower with topical application.

Following topical administration of methoxsalen, the treated skin should be protected from sunlight, even through window glass {03} or on a cloudy day, for at least 12 to 48 hours {03} by protective clothing or a sun block product that has a protection factor of at least 15. {07} Furthermore, since the treated skin continues to be sensitive to sunlight for some time after treatment, the patient should avoid overexposure to sunlight for 72 hours following application of methoxsalen. {03} In addition, the patient should not sunbathe anytime during the course of treatment. {09}

Pigmentation may begin after a few weeks of treatment, but significant repigmentation may require 6 to 9 months. {03} Periodic retreatment may be necessary to retain all of the new pigment. {03} Repigmentation occurs most rapidly {03} and is more predictable on fleshy areas {03} (face, {03} abdomen, {03} buttocks {03}) and occurs more slowly {03} and is less effective on the extremities and bony areas (hands {03} and feet {03}).

Tolerance to the effects of methoxsalen may occur when pigmentation precedes erythema by a long period of time. Hyperpigmentation reduces subsequent responsiveness.

Use of psoralen derivatives to promote suntanning has resulted in serious reactions, including acute generalized dermatitis, blistering, and edema; residual edema of the legs and cutaneous damage have been reported.

Temporary withdrawal of therapy is recommended if burning or blistering of skin occurs.

Dilution to a strength of 1:1000 or 1:10,000 is sometimes necessary to avoid serious reactions.


Topical Dosage Forms

METHOXSALEN TOPICAL SOLUTION USP

Usual adult and adolescent dose
Repigmenting agent (topical)
The topical solution should be applied to a small, well-defined vitiliginous lesion, allowed to dry for one to two minutes, then reapplied. This is done two to two and one-half hours before measured periods of UVA exposure. Following exposure, the lesions should be washed with soap and water {03} and protected with an opaque sunscreen.

Sunlight—Initial exposure time should not exceed one minute and should be increased subsequently with caution.

Artificial light—Initial exposure time should not exceed one-half of the time that produces erythema after sunlight exposure, or should be based on the minimal phototoxic dose (MPD) and manufacturer's directions for the specific light source being used. The MPD can be determined by irradiating several areas of skin 2 cm in diameter; a range of light-exposure times is used and the time that produces erythema at seventy-two hours after exposure is the MPD.


Note: The manufacturer recommends once-weekly treatment; {03} however, some clinicians recommend treatment every three to five days.


Usual pediatric dose
Repigmenting agent (topical)
Children up to 12 years of age: Dosage has not been established. {03}

Children 12 years of age and over: See Usual adult and adolescent dose. {09}


Strength(s) usually available
U.S.—


1% (Rx) [Oxsoralen Lotion (alcohol 71%) (acetone){03}{10}]

Canada—


1% (Rx) [Oxsoralen Lotion{11}] [UltraMOP Lotion{06}{12}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Note: Do not dispense to the patient for use at home. {03}




Revised: 05/26/1994



References
  1. Indications Index review, 11/86.
  1. Methoxsalen hard capsule package insert (Elder—US), Rev 7/83, Rec 5/87.
  1. Methoxsalen topical package insert (Elder—US), Rev 12/85, Rec 6/88.
  1. Panel comment, 3/87.
  1. Fleeger CA, editor. USAN 1988. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1987: 337.
  1. Ultramop Lotion (Canderm Pharmacal). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 23rd ed. Ottawa: Canadian Pharmaceutical Association, 1988: 970.
  1. Panel comments, 12/86.
  1. Panel comments, 10/88.
  1. Panel comment, 7/89.
  1. Oxsoralen Lotion (ICN). In: PDR Physicians' desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data, 1994: 1051-2.
  1. Oxsoralen (ICN). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 28th ed. Ottawa: Canadian Pharmaceutical Association, 1993: 897.
  1. Ultramop Lotion (Canderm Pharmacal). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 28th ed. Ottawa: Canadian Pharmaceutical Association, 1993: 1282.
  1. Lookingbill DP, Marks JG. Principles of dermatology. Philadelphia: WB Saunders, Co., 1986: 52, 126-7.
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