Uvadex Drug Information
Generic name: METHOXSALEN
Photoactivated Radical Generator [EPC] Psoralen [EPC]
Uses of Uvadex
® (methoxsalen) Sterile Solution is indicated for extracorporeal administration with the THERAKOS ® CELLEX ® Photopheresis System in the palliative treatment of the skin manifestations of Cutaneous T-Cell Lymphoma (CTCL) that is unresponsive to other forms of treatment.
Dosage & Administration of Uvadex
| TREATMENT VOLUME × 0.017 = mL of UVADEX® for each treatment | ||
| Example: Treatment volume of 240 mL × 0.017 = 4.1 mL of UVADEX® | ||
Side Effects of Uvadex
Side effects of photopheresis (UVADEX ® used with THERAKOS ® Photopheresis Systems) were primarily related to hypotension secondary to changes in extracorporeal volume (>1%). In study CTCL 3 (UVADEX ® ), six serious cardiovascular adverse experiences were reported in five patients (5/51, 10%). Five of these six events were not related to photopheresis and did not interfere with the scheduled photopheresis treatments. One patient (1/51, 2%) with ischemic heart disease had an arrhythmia after the first day of photopheresis that was resolved the next day. Six infections were also reported in five patients.
Two of the six events were Hickman catheter infections in one patient, which did not interrupt the scheduled photopheresis. The other four infections were not related to photopheresis and did not interfere with scheduled treatments. POSTMARKETING Adverse reactions reported from postmarketing experience include nausea, dysgeusia, photosensitivity reaction, pyrexia and hypersensitivity reactions including anaphylaxis and rash.
Warnings & Cautions for Uvadex
Concomitant Therapy 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, halogenated salicylanilides (bacteriostatic soaps), sulfonamides, tetracyclines, thiazides, and certain organic staining dyes such as methylene blue, toluidine blue, rose bengal and methyl orange may be at greater risk for photosensitivity reactions with UVADEX ®. Carcinogenicity, Mutagenesis, Impairment of Fertility Oral administration of methoxsalen followed by cutaneous UVA exposure (PUVA therapy) is carcinogenic. In a prospective study of 1380 patients given PUVA therapy for psoriasis, 237 patients developed 1422 cutaneous squamous cell cancers. This observed incidence of cutaneous carcinoma is 17.6 times that expected for the general population.
Previous cutaneous exposure to tar and UVB treatment, ionizing radiation or arsenic increased the risk of developing skin carcinomas after PUVA therapy. Because the dose of methoxsalen with UVADEX ® therapy is about 200 times less than with PUVA and the skin is not exposed to high cumulative doses of UVA light, the risk of developing skin cancer following UVADEX ® therapy may be lower. Methoxsalen was carcinogenic in male rats that were given the drug by oral gavage five days per week for 103 weeks at doses of 37.5 and 75 mg/kg.
The 37.5 mg/kg dose is about 1900 times greater than a single human methoxsalen dose during extracorporeal photopheresis treatment on a body surface area basis. The neoplastic lesions in rats included adenomas and adenocarcinomas of the tubular epithelium of the kidneys, carcinoma or squamous cell carcinoma of the Zymbal gland and alveolar or bronchiolar adenomas. Topical or intraperitoneal methoxsalen is a potent photo-carcinogen in albino mice and hairless mice.
With S9 activation, methoxsalen is mutagenic in the Ames test. In the absence of S9 activation and UV light, methoxsalen is clastogenic in vitro (sister chromatid exchange and chromosome aberrations in Chinese hamster ovary cells). Methoxsalen also causes DNA damage, interstrand cross-links and errors in DNA repair. Pregnancy Methoxsalen may cause fetal harm when given to a pregnant woman.
Doses of 80 to 160 mg/kg/day given during organogenesis caused significant fetal toxicity in rats. The lowest of these doses, 80 mg/kg/day, is over 4000 times greater than a single dose of UVADEX ® on a mg/m 2 basis. Fetal toxicity was associated with significant maternal weight loss, anorexia and increased relative liver weight.
Signs of fetal toxicity included increased fetal mortality, increased resorptions, late fetal death, fewer fetuses per litter, and decreased fetal weight. Methoxsalen caused an increase in skeletal malformation and variations at doses of 80 mg/kg/day and above. There are no adequate and well-controlled studies of methoxsalen in pregnant women.
If UVADEX ® is used during pregnancy, or if the patient becomes pregnant while receiving UVADEX ®, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Photosensitivity Severe photosensitivity can occur in patients treated with UVADEX ®. Advise patients to wear UVA absorbing, wrap-around sunglasses and cover exposed skin or use a sunblock (SP 15 or higher), and avoid all exposure to sunlight for twenty-four hours following photopheresis treatment.
See Precautions section for additional information.
Drug Interactions with Uvadex
Drug Interactions See Warnings Section.
Pregnancy Safety for Uvadex
Pregnancy Methoxsalen may cause fetal harm when given to a pregnant woman. Doses of 80 to 160 mg/kg/day given during organogenesis caused significant fetal toxicity in rats. The lowest of these doses, 80 mg/kg/day, is over 4000 times greater than a single dose of UVADEX ® on a mg/m 2 basis.
Fetal toxicity was associated with significant maternal weight loss, anorexia and increased relative liver weight. Signs of fetal toxicity included increased fetal mortality, increased resorptions, late fetal death, fewer fetuses per litter, and decreased fetal weight. Methoxsalen caused an increase in skeletal malformation and variations at doses of 80 mg/kg/day and above.
There are no adequate and well-controlled studies of methoxsalen in pregnant women. If UVADEX ® is used during pregnancy, or if the patient becomes pregnant while receiving UVADEX ®, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
Pediatric Use of Uvadex
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.
Contraindications for Uvadex
® (methoxsalen) Sterile Solution is contraindicated in patients exhibiting idiosyncratic or hypersensitivity reactions to methoxsalen, other psoralen compounds or any of the excipients. Patients possessing a specific history of a light sensitive disease state should not initiate methoxsalen therapy. Diseases associated with photosensitivity include lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum and albinism.
UVADEX ® Sterile Solution is contraindicated in patients with aphakia, because of the significantly increased risk of retinal damage due to the absence of lenses. Patients should not receive UVADEX ® if they have any contraindications to the photopheresis procedure.
Overdosage Information for Uvadex
In the event of overdosage, the patient should be kept in a darkened room for at least 24 hours.
Clinical Studies of Uvadex
Three single-arm studies were performed to evaluate the effectiveness of photopheresis in the treatment of the skin manifestations of Cutaneous T-Cell Lymphoma (CTCL). In the first study (CTCL 1), 39 patients were treated with the oral formulation of methoxsalen in conjunction with the UVAR Photopheresis System. The second study (CTCL 2) was a 5-year post approval follow-up of 57 CTCL patients that was conducted to evaluate long-term safety. This study also used the oral dosage formulation of methoxsalen.
In the third study (CTCL 3), 51 patients were treated with the UVADEX ® formulation of methoxsalen in conjunction with the UVAR Photopheresis System. In study CTCL 3, 86% of the patients were Caucasian, the median age was 62 years, and the average number of prior therapies was 4.3. In study CTCL 1, prednisone up to 10 mg/day was permitted in addition to topical steroids. In CTCL 2, there was no concomitant medication restriction.
In CTCL 3, topical steroids were permitted only for the treatment of fissures on the soles of the feet and the palms of hands. All other steroids, topical or systemic, were prohibited. In all three studies, patients were initially treated on two consecutive days every four to five weeks.
If the patient did not respond after four cycles, treatment was accelerated to two consecutive days every other week. If the patient did not respond after four cycles at the accelerated schedule, the patient was treated on two consecutive days every week. If the patient still did not respond after four cycles of weekly treatments, the schedule was increased to three consecutive days every week for three cycles.
In study CTCL 3, 15 of the 17 responses were seen within six months of treatment. Only two patients responded to treatment after six months. Clinical experience does not extend beyond this treatment frequency and there is no evidence to show that treatment with UVADEX ® beyond six months or using a different schedule provided additional benefit.
Overall skin scores were used in the clinical studies of photopheresis to assess the patient's response to treatment. The patient's baseline skin score was used for comparison with subsequent scores. A 25% reduction in skin score maintained for four consecutive weeks was considered a successful response to photopheresis therapy.
Table 1 indicates the percent of successful responses within six months of beginning therapy for all patients who received at least one course of photopheresis. Only patients with patch plaque, extensive plaque and erythrodermic disease were enrolled in these studies. No patients with disease in the tumor phase were treated.
There are no data available regarding the efficacy of UVADEX ® in patients with disease in the tumor phase. Table 1: Percentage of Successful Responses Within Six Months of Beginning Therapy Study Response % Within Six Months CTCL 3 (UVADEX ® ) 17/51 CTCL 2 (oral methoxsalen) 16/57 CTCL 1 (oral methoxsalen) 21/39 Although the response rate with UVADEX ® in CTCL 3 was similar to with oral methoxsalen in CTCL 2, the possibility that UVADEX ® is inferior in efficacy to oral methoxsalen cannot be excluded due to the design and size of the clinical trials. The higher response rate with oral methoxsalen in CTCL 1 may be partly due to patients receiving more treatments (mean of 64 in CTCL 1, 31 in CTCL 2, and 20 in CTCL 3), and to the administration of systemic steroids in CTCL 1. Retrospective analyses of three clinical benefit parameters from the Body Area Severity Scores in CTCL 3 suggested a correlation between skin score response and improvement in edema, scaling and resolution of fissures.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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