III. INDICATIONS AND USAGE
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.
Photochemotherapy (methoxsalen with long wave ultraviolet radiation) is indicated for the repigmentation of idiopathic vitiligo.
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.
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:
Additional drug dosage directions are as follows:
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.
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.
Dosage Increase: Dosage may be increased by 10 mg. after the fifteenth treatment under the conditions outlined in section XI.B.4.b.
X. UVA RADIATION SOURCE SPECIFICATIONS & INFORMATION
A. IRRADIANCE UNIFORMITY: (For photopheresis, refer to the UVAR* System Operator’s Manual.)
The following specifications should be met with the window of the detector held in a vertical plane:
Vertical variation: For readings taken at any point along the vertical center axis of the chamber (to within 15 cm from the top and bottom), the lowest reading should not be less than 70 percent of the highest reading.
Horizontal variation: Throughout any specific horizontal plane, the lowest reading must be at least 80 percent of the highest reading, excluding the peripheral 3 cm of the patient treatment space.
B. PATIENT SAFETY FEATURES:
The following safety features should be present: (1) Protection from electrical hazard: All units should be grounded and conform to applicable electrical codes. The patient or operator should not be able to touch any live electrical parts. There should be ground fault protection. (2) Protective shielding of lamps: The patient should not be able to come in contact with the bare lamps. In the event of lamp breakage, the patient should not be exposed to broken lamp components. (3) Hand rails and hand holds: Appropriate supports should be available to the patient. (4) Patient viewing window: A window which blocks UV should be provided for viewing the patient during treatment. (5) Door and latches: Patients should be able to open the door from the inside with only slight pressure to the door. (6) Non-skid floor: The floor should be of a non-skid nature. (7) Thermoregulation: Sufficient air flow should be provided for patient safety and comfort, limiting temperature within the UVA radiator cabinet to approximately less than 100°F. (8) Timer: The irradiator should be equipped with an automatic timer which terminates the exposure at the conclusion of a pre-set time interval. (9) Patient alarm device: An alarm device within the UVA irradiator chamber should be accessible to the patient for emergency activation. (10) Danger label: The unit should have a label prominently displayed which reads as follows:
DANGER – Ultraviolet Radiation – Follow your physician’s instructions – Failure to use protective eyewear may result in eye injury.
C. UVA EXPOSURE DOSIMETRY MEASUREMENTS:
The maximum radiant exposure or irradiance (within ±15 percent) of UVA (320-400 nm) delivered to the patient should be determined by using an appropriate radiometer calibrated to be read in Joules/cm2 or mW/cm2. In the absence of a standard measuring technique approved by the National Bureau of Standards, the system should use a detector corrected to a cosine spatial response. The use and recalibration frequency of such a radiometer for a specific UVA irradiator chamber should be specified by the manufacturer because the UVA dose (exposure) is determined by the design of the irradiator, the number of lamps, and the age of the lamps. If irradiance is measured, the radiometer reading in mW/cm2 is used to calculate the exposure time in minutes to deliver the required UVA dose in Joules/cm2 to a patient in the UVA irradiator cabinet. The equation is:
|Exposure Time||Desired UVA Dose (J/cm2)|
|in minutes||0.06 x Irradiance (mW/cm2)|
Overexposure due to human error should be minimized by using an accurate automatic timing device, which is set by the operator and controlled by energizing and de-energizing the UVA irradiator lamp. The timing device calibration interval should be specified by the manufacturer. Safety systems should be included to minimize the possibility of delivering a UVA exposure which exceeds the prescribed dose, in the event the timer or radiometer should malfunction.
D. UVA SPECTRAL OUTPUT DISTRIBUTION:
The spectral distributions of the lamps should meet the following specifications:
|Wavelength Band (Nanometers)||Output1|
|1As a percentage of total irradiance between 320 and 400 nanometers.|
|310 to 320||1 to 3|
|320 to 330||4 to 8|
|330 to 340||11 to 17|
|340 to 350||18 to 25|
|350 to 360||19 to 28|
|360 to 370||15 to 23|
|370 to 380||8 to 12|
|380 to 390||3 to 7|
|390 to 400||1 to 3|
XII. HOW SUPPLIED:
8-MOP Capsules, each containing 10 mg of methoxsalen (8-methoxypsoralen) are available in pink-colored hard gelatin capsules in amber glass bottles of 50 (NDC 0187-0651-42), with ICN imprinted on the cap of the capsule and 600 imprinted on the body of the capsule.
Store at 25°C (77°F); excursions permitted to 15°C- 30°C (59°F- 86°F).
Pathak, M.A., Kramer, D.M., Fitzpatrick, T.B.: Photobiology and Photochemistry of Furocoumarins (Psoralens), SUNLIGHT AND MAN: Normal and Abnormal Photobiologic Responses. Edited by M.A. Pathak, L.C. Harbor, M. Seiji et al. University of Tokyo Press. 1974, pp. 335-368.
Artuc, M., Stuettgen, G., Schalla, W., Schaefer, H., and Gazith, J.: Reversible binding of 5- and 8-methoxypsoralen to human serum proteins (albumin) and to epidermis in vitro: Brit. J. Dermat. 101, pp. 669-677 (1979).
Mandula, B.B., Pathak, M.A., Nakayama, Y., and Davidson, S.J.: Induction of mixed-function oxidases in mouse liver by psoralens., Ibid, 99, pp. 687-692 (1978).
Pathak, M.A., Fitzpatrick, T.B., Parrish, J.A.: PSORIASIS, Proceedings of the Second International Symposium. Edited by E.M. Farber, A.J. Cox, Yorke Medical Books, pp. 262-265 (1977).
Dall’ Acqua, F., Marciani, S., Ciavatta, L, Rodighiero, G.: Formation of interstrand cross-linkings in the photoreactions between furocoumarins and DNA; Z Naturforsch (B), 26, pp. 561-569 (1971).
Cole, R.S.: Light-induced cross-linkings of DNA in the presence of a furocoumarin (psoralen), Biochem. Biophys. Acta, 217, pp. 30-39 (1970).
Musajo, L., Rodighiero, G., Caporale, G., Dall’ Acqua, F., Marciani, S., Bordin, F., Baccichetti, F., Bevilacqua, R.: Photoreactions between Skin-Photosensitizing Furocoumarins and Nucleic Acids, SUNLIGHT AND MAN; Normal and Abnormal Photobiologic Responses. Edited by M.A. Pathak, L.C. Harber, M. Seiji et al. University of Tokyo Press, pp. 369-387 (1974).
Dall’ Acqua, F., Vedaldi, D., Bordin, F., and Rodighiero, G.: New studies in the interaction between 8-methoxypsoralen and DNA in vitro; J. Investigative Dermat., 73, pp. 191-197 (1979).
Yoshikawa, K., Mori, N., Sakakibara, S., Mizuno, N., Song, P.: Photo-Conjugation of 8-methoxypsoralen with Proteins; Photochem. & Photobiol. 29, pp. 1127-1133 (1979).
Ortonne, J. P., MacDonald, D.M., Micoud, A., Thivolet, J.: PUVA-induced repigmentation of vitiligo: a histochemical (split-DOPA) and ultra-structural study: Brit. J. of Dermat., 101, pp. 1-12 (1979).
Hakim, R.E., Griffin, A.C., Knox, J.M.: Erythema and tumor formation in methoxsalen treated mice exposed to fluorescent light; Arch. Dermatol. 82, pp. 572-577 (1960).
Pathak, M.A., Daniels, F., Hopkins, C.E., Fitzpatrick, T.B.: Ultraviolet carcinogenesis in albino and pigmented mice receiving furocoumarins: psoralens and 8-methoxypsoralen, Nature 183, pp. 728-730 (1959).
Stern, R.S., Thibodeau, L.A., Kleinerman, R.A., Parrish, J.A., Fitzpatrick, T.B., and 22 Participating Investigators: Risk of Cutaneous Carcinoma in Patients Treated with Oral Methoxsalen Photochemotherapy for Psoriasis: NEJM, 300. No. 15, pp. 809-813 (1979).
Stern, R.S., Parrish, J.A., Zierler, S.: Skin Carcinoma in Patients with Psoriasis Treated with Topical Tar and Artificial Ultraviolet Radiation. Lancet, 1, pp. 732-735 (1980).
Roenigk, Jr., H.H., and 12 Cooperating Investigators: Skin Cancer in the PUVA-48 Cooperative Study of Psoriasis. Program for Forty-First Annual Meeting for The Society of Investigative Dermatology, Inc., Sheraton Washington Hotel, Washington, D.C., May 12, 13, and 14, 1980. Abstracts JID, 74, No. 4, p. 250 (April, 1980).
Stern et al., Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-up Study. New England Journal of Medicine, 336:1041-1045, (April 10, 1997).
Mosher, D.B., Pathak, M.A., Harris, T.J., Fitzpatrick, T.B.: Development of Cutaneous Lesions in Vitiligo During Long-Term PUVA Therapy. Program for Forty-First Annual Meeting for The Society for Investigative Dermatology, Inc., Sheraton Washington Hotel, Washington, D.C., May 12, 13, and 14, 1980. Abstracts JID, 74, No. 4, p. 259 (April, 1980).
Cloud, T.M., Hakim, R., Griffin, A.C.: Photosensitization of the eye with methoxsalen. I. Acute effects; Arch. Ophthalmol. 64, pp. 346-352 (1960).
Cloud, T.M., Hakim, R., Griffin, A.C.: Photosensitization of the eye with methoxsalen. II. Chronic effects, Ibid, 66, pp. 689-694 (1961).
Freeman, R.G., Troll, D.: Photosensitization of the eye by 8-methoxypsoralen, JID, 53, pp. 449-453 (1969).
Lerman, S., Megaw, J., Willis, I.: Potential ocular complications from PUVA therapy and their prevention; J. Invest. Dermtat., 74, pp. 197-199 (1980).
2579-03 EL Manufactured by Sun Pharmaceuticals Industries, Inc.
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Manufactured for Valeant Pharmaceuticals North America
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