Oxsoralen-Ultra

Methoxsalen is a naturally occurring substance that is reactive to light. It works by enhancing the body's sensitivity to ultraviolet light A (UVA).

Methoxsalen is used in combination with UVA light therapy to treat severe psoriasis. Methoxsalen is usually given after other psoriasis medicines have been tried without success.

Methoxsalen can cause harmful effects on your vision and on your skin (premature aging or skin cancer). This medicine is used only for severe psoriasis that has not improved with other treatments. You must remain under the care of a doctor while taking methoxsalen.

Methoxsalen may also be used for purposes not listed in this medication guide.

You should not use methoxsalen if you have a condition that makes you more sensitive to light (lupus, porphyria, albinism, and others), or if you have a history of skin cancer or damage to the lenses of your eyes due to surgery, injury, or genetic condition.

Methoxsalen can cause harmful effects on your vision and on your skin (premature aging or skin cancer). This medicine is used only for severe psoriasis that has not improved with other treatments. You must remain under the care of a doctor while taking methoxsalen.

If your doctor changes your brand, strength, or type of methoxsalen, your dosage needs and UVA light therapy schedule may change. Oxsoralen-Ultra and 8-Mop are not equivalent medicines and may not have the same dose or schedule. Ask your pharmacist if you have any questions about the new kind of methoxsalen you receive at the pharmacy.

You should not use this medicine if you are allergic to methoxsalen or similar "psoralen" medicines, or if you have:

• a history of skin cancer;
• lupus, porphyria, albinism, or other conditions that make you more sensitive to light; or
• damage to the lenses of your eyes caused by surgery, injury, or genetic condition.

Before your UVA treatment: Do not expose your skin to sunlight for at least 24 hours before you take methoxsalen. Avoid applying sunscreen to areas of psoriasis that will be treated with UVA therapy.

You may need to have your eyes examined before you start taking methoxsalen.

To make sure methoxsalen is safe for you, tell your doctor if you have:

• heart disease;
• liver disease;
• a skin pigment disorder;
• a history of cataracts;
• a history of basal cell carcinoma;
• if you are extremely sensitive to sunlight;
• if you have ever received radiation or x-ray therapy, or used arsenic trioxide (Trisenox); or
• if you have recently gained or lost weight.

FDA pregnancy category C. It is not known whether methoxsalen will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether methoxsalen passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Avoid exposure to sunlight or artificial UV rays other than your scheduled light therapy treatments.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with methoxsalen. Methoxsalen can make your skin even more sensitive to sunlight if you also use certain other medicines, especially:

• griseofulvin;
• nalidixic acid;
• an antibiotic (such as ciprofloxacin (Cipro), doxycycline, levofloxacin (Levaquin), minocycline, ofloxacin, tetracycline), and others;
• a bacteriostatic soap;
• coal tar applied to the skin or scalp (Neutrogena T/Gel, Psoriasin, Tegrin Medicated, and others);
• a diuretic or "water pill";
• medicine to treat mental illness (such as chlorpromazine, fluphenazine, prochlorperazine, thioridazine, and others);
• a staining dye such as methylene blue, toluene blue, rose bengal, or methyl orange; or
• a sulfa drug (Bactrim, SMX-TMP or SMZ-TMP, and others).

This list is not complete. Other drugs may interact with methoxsalen, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You will take methoxsalen a certain number of hours before you are scheduled to receive UVA treatment. The soft gelatin capsule (Oxsoralen-Ultra) is more easily absorbed in the body than the hard gelatin capsule (8-Mop). The timing of your dose will depend on which type of capsule you are taking.

You may also need to keep taking methoxsalen after your UVA treatment, either for a short time or as needed. Follow your doctor's dosing instructions very carefully.

Take this medicine with low-fat food or milk if it upsets your stomach.

If your doctor changes your brand, strength, or type of methoxsalen, your dosage needs and UVA light therapy schedule may change. Oxsoralen-Ultra and 8-Mop are not equivalent medicines and may not have the same dose or schedule. Ask your pharmacist if you have any questions about the new kind of methoxsalen you receive at the pharmacy.

Methoxsalen will make your skin more sensitive to sunlight and sunburn may result, which could interfere with your psoriasis treatment.

For at least 8 hours after you take methoxsalen:

• Avoid exposure to sunlight or tanning beds.
• Even sunlight shining through clouds or through a glass window can expose you to harmful UV rays.
• Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors or near a window.
• Do not apply sunscreen to areas of active psoriasis that will be treated with UVA therapy.

For 24 to 48 hours after you receive UVA treatment:

• You must protect your skin and eyes from natural sunlight (even sun shining through a window).
• Wear sunglasses for at least 24 hours after treatment.
• For utmost protection, wear a pair of wraparound UVA-absorbing sunglasses, even while you are indoors near a window.
• Do not expose your skin to sunlight or tanning beds for at least 48 hours. Wear protective clothing including a hat and gloves. Use a sunscreen with a minimum SPF of 30, and apply it to all uncovered skin areas exposed to light.

You may develop cataracts if you do not properly protect your eyes after you are treated with methoxsalen and UVA treatment.

Follow your doctor's instructions about applying topical psoriasis medications or any moisturizing lotions after your methoxsalen and UVA treatment.

While taking methoxsalen, check your skin regularly for signs of skin cancer, such as a small growth or nodule, a scaly or crusted lesion, a brownish spot or speckles, or a change in the size, color, or feel of a mole. After receiving UVA treatments, you may need to check your skin for signs of cancer throughout the rest of your life.

Store at room temperature away from moisture, heat, and light.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. You will be extremely sensitive to light after an overdose.

Call your doctor for instructions if you miss your dose or forget to take the medicine within the proper amount of time before your scheduled UVA treatment. You may need to reschedule your light therapy appointment if you have not taken methoxsalen at the correct time.

Methoxsalen belongs to the group of medicines called psoralens. It is used along with ultraviolet light (found in sunlight and some special lamps) in a treatment called PUVA to treat vitiligo, a disease in which skin color is lost, and psoriasis, a skin condition associated with red and scaly patches.

Methoxsalen is also used with ultraviolet light in the treatment of white blood cells. This treatment is called photopheresis and is used to treat the skin problems associated with mycosis fungoides, which is a type of lymphoma.

Methoxsalen may also be used for other conditions as determined by your doctor.

This medicine is available only with your doctor's prescription.

This section provides information on the proper use of a number of products that contain methoxsalen. It may not be specific to Oxsoralen-Ultra. Please read with care.

Eating certain foods while you are taking methoxsalen may increase your skin's sensitivity to sunlight. To help prevent this, avoid eating limes, figs, parsley, parsnips, mustard, carrots, and celery while you are being treated with this medicine.

Methoxsalen usually comes with patient directions. Read them carefully before using this medicine.

This medicine may take 6 to 8 weeks to really help your condition. Do not increase the amount of methoxsalen you are taking or spend extra time in the sunlight or under an ultraviolet lamp. This will not make the medicine act any more quickly and may result in a serious burn.

If this medicine upsets your stomach:

• Patients taking the hard gelatin capsules may take them with food or milk.
• Patients taking the soft gelatin capsules may take them with low-fat food or low-fat milk.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (hard gelatin capsule):
  • For treating mycosis fungoides and psoriasis:
    • Adults and children 12 years of age and over—Dose is based on body weight and must be determined by your doctor. However, the usual dose is 0.6 mg per kilogram (kg) (0.27 mg per pound) of body weight taken two hours before UVA exposure. This treatment (methoxsalen and UVA) is given two or three times a week with the treatment spaced at least forty-eight hours apart.
    • Children up to 12 years of age—Dose must be determined by your doctor.
  • For vitiligo:
    • Adults and children 12 years of age and over—20 milligrams (mg) per day taken two to four hours before ultraviolet light A (UVA) exposure. This treatment (methoxsalen and UVA) is given two or three times a week with the treatment spaced at least forty-eight hours apart.
    • Children up to 12 years of age—Dose must be determined by your doctor.
• For oral dosage form (soft gelatin capsule):
  • For psoriasis:
    • Adults and children 12 years of age and over—Dose is based on body weight and must be determined by your doctor. The usual dose is 0.4 mg per kg (0.18 mg per pound) of body weight taken one and one-half to two hours before UVA exposure. This treatment (methoxsalen and UVA) is given two or three times a week, with the treatment spaced at least forty-eight hours apart.
    • Children up to 12 years of age—Dose must be determined by your doctor.

Missed Dose

Call your doctor or pharmacist for instructions.

If you are late in taking, or miss taking, a dose of this medicine, notify your doctor so your light treatment can be rescheduled. Remember that exposure to sunlight or ultraviolet light must take place a certain number of hours after you take the medicine or it will not work. For patients taking the hard gelatin capsules, this is 2 to 4 hours. For patients taking the soft gelatin capsules, this is 1½ to 2 hours. If you have any questions about this, check with your doctor.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Oxsoralen-Ultra (methoxsalen capsules, USP) contains 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:

Oxsoralen-Ultra is 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.

A. GENERAL - APPLICABLE TO 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

   1. 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 of patient well-being and comfort.

   2. Patients must avoid sun exposure, even through window glass or cloud cover, for at least 8 hours after methoxsalen ingestion. If sun exposure cannot 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

   1. 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.

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

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

4. AFTER COMBINED METHOXSALEN/UVA THERAPY

   1. UVA-absorbing wrap-around sunglasses should be worn during daylight for 24 hours after combined methoxsalen/UVA therapy.

   2. Patients should not sunbathe for 48 hours after therapy. Erythema and/or burning due to photochemotherapy and sunburn due to sun exposure are additive.

B. INFORMATION FOR PATIENTS:

See accompanying Patient Package Insert.

C. LABORATORY TESTS:

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

2. Patients should have routine laboratory tests prior to the start of therapy and at regular periods thereafter if patients are on extended treatments.

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 with reproductive capacity 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, either methoxsalen ingestion or nursing should be discontinued.

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.

I. GERIATRIC USE:

Clinical studies with Oxsoralen-Ultra capsules did not include sufficient numbers of subjects aged 65 and over to determine whether elderly subjects responded differently from younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

In the event of methoxsalen overdosage, induce emesis and keep the patient in a darkened room for at least 24 hours. Emesis is most beneficial within the first 2 to 3 hours after ingestion of methoxsalen, since maximum blood levels are reached by this time.

Applies to methoxsalen: oral capsule, oral capsule liquid filled

Other dosage forms:

• injection injectable, injection solution

Along with its needed effects, methoxsalen (the active ingredient contained in Oxsoralen-Ultra) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking methoxsalen:

• Blistering and peeling of skin
• reddened, sore skin
• swelling (especially of feet or lower legs)

Some side effects of methoxsalen may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Itching of skin
• nausea

• Dizziness
• headache
• mental depression
• nervousness
• trouble in sleeping

Treatment with this medicine usually causes a slight reddening of your skin 24 to 48 hours after the treatment. This is an expected effect and is no cause for concern. However, check with your doctor right away if your skin becomes sore and red or blistered.

There is an increased risk of developing skin cancer after use of methoxsalen. You should check your body regularly and show your doctor any skin sores that do not heal, new skin growths, and skin growths that have changed in the way they look or feel.

Premature aging of the skin may occur as a result of prolonged methoxsalen therapy. This effect is permanent and is similar to what happens when a person sunbathes for long periods of time.

Applies to methoxsalen: compounding powder, injectable solution, oral capsule

Dermatologic

Dermatologic side effects have included mild to serious skin burns, premature aging of the skin, pruritus, inflammation, erythema, rash (nonspecific), edema, extension of psoriasis, cutaneous tenderness, hypopigmentation, keratosis, folliculitis, dermal vessel damage, longer duration of epidermal and dermal abnormalities, miliaria, urticaria, vesiculation formation, and bullae formation. Postmarketing dermatologic side effects have included rash.[Ref]

Cardiovascular

Cardiovascular side effects are mostly associated with methoxsalen (the active ingredient contained in Oxsoralen-Ultra) sterile solution and have included arrhythmia and serious (nonspecific) cardiovascular adverse experiences. Hypotension and dizziness have been associated with the sterile solution and the oral administration of methoxsalen.[Ref]

Immunologic

Immunologic side effects associated with the sterile solution have included infections (nonspecific) and hickman catheter infections. Immunologic side effect with oral administration of methoxsalen (the active ingredient contained in Oxsoralen-Ultra) has been herpes simplex.[Ref]

Oncologic

Oncologic side effects have included cutaneous squamous cell cancers, malignant melanoma, and basal cell carcinoma.[Ref]

Psychiatric

Psychiatric side effects have included depression.[Ref]

Gastrointestinal

Gastrointestinal side effects have included unspecified gastrointestinal disturbances. Postmarketing gastrointestinal side effects have included nausea and dysgeusia.[Ref]

General

General side effects have included malaise and headache. Postmarketing general side effects have included pyrexia.[Ref]

Ocular

Ocular side effects have included cataracts.[Ref]

Hypersensitivity

Hypersensitivity side effects have included postmarketing reports of allergic reaction.[Ref]

Some side effects of Oxsoralen-Ultra may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.