Methoxsalen (injection)

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Methoxsalen (injection)
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shanshan Cen, M.D. [2]

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Black Box Warning

WARNING:
See full prescribing information for complete Boxed Warning.
UVADEX® (methoxsalen) Sterile Solution should be used only by physicians who have special competence in the diagnosis and treatment of cutaneous T-cell lymphoma and who have special training and experience in the THERAKOS® UVAR XTS® or THERAKOS® CELLEX® Photopheresis System. Please consult the appropriate Operator's Manual before using this product.

Overview

Methoxsalen (injection) is a naturally occurring photoactive substance that is FDA approved for the treatment of the skin manifestations of Cutaneous T-Cell Lymphoma (CTCL) that is unresponsive to other forms of treatment. There is a Black Box Warning for this drug as shown here. Common adverse reactions include erythema, pain of skin, pruritus, nausea, dizziness, headache, fatigue.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

UVADEX® (methoxsalen) Sterile Solution is indicated for extracorporeal administration with the THERAKOS® UVAR XTS® or 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

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® UVAR XTS® or 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® UVAR XTS® or 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® UVAR XTS® or 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® UVAR XTS® or 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 Photactivation Phase using the formula:

  • TREATMENT VOLUME X 0.017 = mL of UVADEX ® for each treatment
  • Example: Treatment volume of 240 mL X 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.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methoxsalen (injection) in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methoxsalen (injection) in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Methoxsalen (injection) in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methoxsalen (injection) in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methoxsalen (injection) in pediatric patients.

Contraindications

PHOTOSENSITIVITY

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.

Warnings

WARNING:
See full prescribing information for complete Boxed Warning.
UVADEX® (methoxsalen) Sterile Solution should be used only by physicians who have special competence in the diagnosis and treatment of cutaneous T-cell lymphoma and who have special training and experience in the THERAKOS® UVAR XTS® or THERAKOS® CELLEX® Photopheresis System. Please consult the appropriate Operator's Manual before using this product.

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/m2 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.

Adverse Reactions

Clinical Trials Experience

Side effects of photopheresis (UVADEX® used with the THERAKOS® Photopheresis System) 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 Experience

An analysis of postmarketing data shows the following events occurred with an incidence of <0.01%: rash, allergic reaction, pyrexia, nausea, dysgeusia.

Drug Interactions

See WARNINGS Section.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Methoxsalen (injection) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Methoxsalen (injection) during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Methoxsalen (injection) with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Methoxsalen (injection) with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Methoxsalen (injection) with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Methoxsalen (injection) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Methoxsalen (injection) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Methoxsalen (injection) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Methoxsalen (injection) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Methoxsalen (injection) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Methoxsalen (injection) in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Methoxsalen (injection) in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Methoxsalen (injection) in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Methoxsalen (injection) in the drug label.

Pharmacology

There is limited information regarding Methoxsalen (injection) Pharmacology in the drug label.

Mechanism of Action

Structure

File:Methoxsalen (injection)01.png
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Methoxsalen (injection) in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Methoxsalen (injection) in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Methoxsalen (injection) in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Methoxsalen (injection) in the drug label.

How Supplied

Storage

There is limited information regarding Methoxsalen (injection) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Methoxsalen (injection) in the drug label.

Precautions with Alcohol

  • Alcohol-Methoxsalen (injection) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. "UVADEX- methoxsalen injection, solution".
  2. "http://www.ismp.org". External link in |title= (help)