Methoxsalen

Description

DESCRIPTION Methoxsalen is a naturally occurring photoactive substance found in the seeds of the Ammi majus (Umbelliferae) plant. It belongs to a group of compounds known as psoralens or furocoumarins. The chemical name of methoxsalen is 9-methoxy-7H-furo[3,2-g][1]-benzopyran-7-one; it has the following structure: Each mL of UVADEX ® (methoxsalen, 8-methoxypsoralen) Sterile Solution contains methoxsalen 20 mcg, propylene glycol 50 mg, sodium chloride 8 mg, sodium acetate 1.75 mg, ethanol 40.550 mg, glacial acetic acid 1.260 mg, and Water for Injection q.s. to 1.0 mL. Glacial acetic acid and sodium hydroxide are used to adjust the pH of the solution if necessary. UVADEX ® is a clear, colorless to pale yellow liquid. UVADEX ® is used in combination with the THERAKOS ® CELLEX ® Photopheresis System to extracorporeally treat leukocyte enriched buffy coat. Chemical Structure

What Is Methoxsalen Used For?

INDICATIONS AND USAGE 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 and Administration

DRUG DOSAGE AND ADMINISTRATION Each UVADEX ® treatment involves collection of leukocytes, photoactivation, and reinfusion of photoactivated cells. UVADEX ® (methoxsalen) Sterile Solution is supplied in 10 mL vials containing 200 mcg of methoxsalen (concentration of 20 mcg/mL). The THERAKOS ® CELLEX ® Photopheresis System Operator's Manual should be consulted before using this product. UVADEX ® should not be diluted. The contents of the vial should be injected into the THERAKOS ® CELLEX ® Photopheresis System immediately after being drawn up into a syringe. Do not inject directly into patients. The UVADEX ® vial is for single use only. Any UVADEX ® that is not used during a procedure should be immediately discarded. UVADEX ® can adsorb onto PVC and plastics, therefore only THERAKOS ® CELLEX ® photopheresis procedural kits supplied for use with the instrument should be used to administer this medicinal product. Once UVADEX ® is drawn into a plastic syringe it should be immediately injected into the photoactivation bag. UVADEX ® exposed to a plastic syringe for more than one hour should be discarded. During treatment with the THERAKOS ® CELLEX ® Photopheresis System, the dosage of UVADEX ® for each treatment will be calculated according to the treatment volume. The prescribed amount of UVADEX ® should be injected into the recirculation bag prior to the Photoactivation Phase using the formula: TREATMENT VOLUME × 0.017 = mL of UVADEX ® for each treatment Example: Treatment volume of 240 mL × 0.017 = 4.1 mL of UVADEX ® Frequency/Schedule of Treatment Normal Treatment Schedule Treatment is given on two consecutive days every four weeks for a minimum of seven treatment cycles (six months). Accelerated Treatment Schedule If the assessment of the patient during the fourth treatment cycle (approximately three months) reveals an increased skin score from the baseline score, the frequency of treatment may be increased to two consecutive treatments every two weeks. If a 25% improvement in the skin score is attained after four consecutive weeks, the regular treatment schedule may resume. Patients who are maintained in the accelerated treatment schedule may receive a maximum of 20 cycles. There is no clinical evidence to show that treatment with UVADEX ® beyond six months or using a different schedule provides additional benefit. In study CTCL 3, 15 of the 17 responses were seen within six months of treatment and only two patients responded to treatment after six months.

Side Effects (Adverse Reactions)

ADVERSE REACTIONS 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.

Drug Interactions

Drug Interactions See Warnings Section.

Contraindications

CONTRAINDICATIONS 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.

Pregnancy and Breastfeeding

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.

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.

Overdosage

OVERDOSAGE In the event of overdosage, the patient should be kept in a darkened room for at least 24 hours.

How Supplied

HOW SUPPLIED UVADEX ® (methoxsalen) Sterile Solution 20 mcg/mL in 10 mL amber glass vials (NDC 64067-216-01), and cartons of 12 vials (NDC 64067-216-01). One vial of 10 mL contains 200 micrograms methoxsalen. The drug product must be stored between 59°F (15°C) and 86°F (30°C)