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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
Methoxsalen soft gelatin capsules (Oxsoralen-Ultra®) may be confused with methoxsalen hard gelatin capsules (8-MOP®, Oxsoralen®); bioavailability and photosensitization onset differ between the two products.
Pronunciation
(meth OKS a len)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Oral: Symptomatic control of severe, recalcitrant disabling psoriasis; repigmentation of idiopathic vitiligo; palliative treatment of skin manifestations of cutaneous T-cell lymphoma (CTCL)
Topical: Repigmentation of idiopathic vitiligo
Extracorporeal: Palliative treatment of skin manifestations of CTCL
Pregnancy Risk Factor
C/D (Uvadex®)
Pregnancy Considerations
Fetal toxicity has been observed in animal studies, however, there are no adequate and well-controlled studies in pregnant women. Use during pregnancy is not recommended. Women of childbearing potential should be advised to avoid pregnancy.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to methoxsalen (psoralens) or any component of the formulation; diseases associated with photosensitivity (eg, albinism, lupus erythematosus, porphyria [cutanea tarda, erythropoietic and variegate], xeroderma pigmentosum); invasive squamous cell cancer; aphakia; melanoma or history of melanoma; children <12 years of age (Oxsoralen® lotion)
Warnings/Precautions
Boxed warnings:
• Experienced physician: See “Other warnings/precautions” below.
• Product interchange: See “Dosage form specific issues” below.
Concerns related to adverse effects:
• Burns: Serious burns may occur from ultraviolet radiation or sunlight (even if exposed through glass) if recommended dose and/or exposure schedule is not maintained.
• Cataracts: Methoxsalen concentrates in the lens; eyes should be shielded from direct and indirect sunlight for 24 hours to prevent possible formation of cataracts.
• Photosensitivity: Avoid sun (including sun lamp) exposure for 8 hours after methoxsalen ingestion. Protective clothing, eyewear, and sunscreen (do not apply sunscreen to psoriatic areas) should be used for 24 hours after combined methoxsalen/UVA therapy. Do not use in sunburned patients until they have fully recovered; pre-existing sunburn may obscure evaluation of response; advise patients to avoid sunbathing for 24 hours prior to treatment and for 48 hours after treatment. Use extreme caution in patients who have significant exposure to the sun through their occupation.
• Skin cancer: Therapy may lead to increased risk of skin cancer (basal cell, melanoma and squamous cell); this risk may be increased with fair skin or prior exposure to prolonged tar and UVB treatment, ionizing radiation, or arsenic.
Disease-related concerns:
• Basal cell carcinoma: Use with caution in patients with multiple basal cell carcinomas or a history of basal cell carcinoma; observe closely.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease (may not be able to tolerate the heat stress or prolonged standing related to UVA treatment conditions).
• CTCL: Appropriate use: For use only if inadequate response to other forms of therapy. Used in conjunction with long wave radiation of white blood cells using the UVAR® photopheresis system.
• Hepatic impairment: Methoxsalen undergoes hepatic metabolism; use with caution in patients with hepatic impairment.
• Psoriasis: Appropriate use: For use only if inadequate response to other therapies when the diagnosis is biopsy proven. Administer only in conjunction with scheduled controlled doses of long wave ultraviolet (UVA) radiation (combination referred to as PUVA).
• Vitiligo: Appropriate use: Used in conjunction with controlled doses of long wave ultraviolet radiation or sunlight. Lotion should only be applied under direct supervision of prescriber and should not be dispensed to the patient.
Concurrent drug therapy issues:
• Photosensitizing agents: Use caution with other (systemic or topical) photosensitizing drugs (eg, thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides, anthralin, coal tar preparations).
Special populations:
• Elderly: Use with caution in the elderly.
• Pediatrics: Safety and efficacy have not been established in children for CTCL or psoriasis and <12 years of age for vitiligo. The long-term effects of treatment (including potential cataract formation, skin cancer development, and premature skin aging) are unknown in children.
Dosage form specific issues:
• Product interchange: [U.S. Boxed Warning]: Soft-gelatin capsule (Oxsoralen-Ultra®) and hard-gelatin capsule (8-MOP®, Oxsoralen®) are not interchangeable; retitration is required if the formulation is changed. Oxsoralen-Ultra® has a greater bioavailability and shorter onset of photosensitization.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced physician with special competence in the diagnosis and treatment of dermatologic diseases.
Adverse Reactions
Frequency not always defined.
Cardiovascular: Edema, hypotension
Central nervous system: Depression, dizziness, headache, insomnia, malaise, nervousness, vertigo
Dermatologic: Pruritus (10%), blistering (painful), bullae formation, burning, erythema, folliculitis, freckling, hypopigmentation, miliaria, peeling of skin, premature aging, rash, skin cancer, tenderness (cutaneous), urticaria, vesiculation
Gastrointestinal: Nausea (10%), gastrointestinal disturbance
Neuromuscular & skeletal: Loss of muscle coordination, leg cramps
Ocular: Cataract
Miscellaneous: Herpes simplex, infection
Metabolism/Transport Effects
Substrate of CYP2A6 (minor); Inhibits CYP1A2 (strong), 2A6 (strong), 2C9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak), 3A4 (weak)
Drug Interactions
Bendamustine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Bendamustine. Concentrations of the active metabolites of bendamustine may be decreased. Risk C: Monitor therapy
CYP1A2 Substrates: CYP1A2 Inhibitors (Strong) may decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP2A6 Substrates: CYP2A6 Inhibitors (Strong) may decrease the metabolism of CYP2A6 Substrates. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: Methoxsalen serum concentrations may be increased if taken with food.
Mechanism of Action
Bonds covalently to pyrimidine bases in DNA, inhibits the synthesis of DNA, and suppresses cell division. The augmented sunburn reaction involves excitation of the methoxsalen molecule by radiation in the long-wave ultraviolet light (UVA), resulting in transference of energy to the methoxsalen molecule producing an excited state (“triplet electronic state”). The molecule, in this “triplet state,” then reacts with cutaneous DNA.
Pharmacodynamics/Kinetics
Protein binding: Reversibly bound to albumin
Metabolism: Hepatic; forms metabolites
Bioavailability: Bioavailability increased with soft-gelatin capsules (Oxsoralen-Ultra®) compared to hard-gelatin capsules (8-MOP®, Oxsoralen®); exposure using Uvadex® with the UVAR® photopheresis system is ~200 times less than with oral methoxsalen administration
Time to peak, serum:
Hard-gelatin capsules (8-MOP®, Oxsoralen®): 1.5-6 hours (peak photosensitivity: ~4 hours)
Soft-gelatin capsules (Oxsoralen-Ultra®): 0.5-4 hours (peak photosensitivity: 1.5-2 hours)
Half-life elimination: ~2 hours
Excretion: Urine (~95% as metabolites)
Dosage
Note: Refer to treatment protocols for UVA exposure guidelines.
Children >12 years and Adults: Vitiligo: Topical (Oxsoralen®): Lotion is applied prior to UVA light exposure, usually no more than once weekly
Adults:
Psoriasis: Oral:
Initial: 10-70 mg 1.5-2 hours (Oxsoralen-Ultra®) or 2 hours (8-MOP®) before exposure to UVA light; dose may be repeated 2-3 times per week, based on UVA exposure; doses must be given at least 48 hours apart. Dosage is based upon patient's body weight and skin type:
<30 kg: 10 mg
30-50 kg: 20 mg
51-65 kg: 30 mg
66-80 kg: 40 mg
81-90 kg: 50 mg
91-115 kg: 60 mg
>115 kg: 70 mg
Note: Dosage may be increased (one time) by 10 mg after 15th treatment if minimal or no response.
Maintenance: When 95% psoriasis clearing achieved, may begin 1 treatment every week for at least 2 treatments; followed by 1 treatment every 2 weeks for at least 2 treatments; then every 3 weeks for at least 2 treatments then as needed to maintain response while minimizing UVA exposure.
Vitiligo:
Oral (8-MOP®): 20 mg 2-4 hours before exposure to UVA light; dose may be repeated based on erythema and tenderness of skin; do not give on 2 consecutive days
CTCL: Extracorporeal (Uvadex®): 200 mcg injected into the photoactivation bag during the collection cycle using the UVAR® photopheresis system (consult user's guide). Treatment schedule: Two consecutive days every 4 weeks for a minimum of 7 treatment cycles, may accelerate to two consecutive days every 2 weeks if skin score worsens (eg, increases from baseline) after assessment during the fourth treatment cycle. If skin score improves by 25% after 4 consecutive weeks of accelerated therapy, may resume regular treatment schedule. Maximum: 20 accelerated therapy cycles.
Administration: Oral
To reduce nausea, oral drug can be administered with food or milk or in 2 divided doses 30 minutes apart.
Administration: Topical
Hands and fingers of person applying the lotion should be protected to prevent possible photosensitization and/or burns.
Monitoring Parameters
CBC with differential (baseline and every 6-12 months), liver and renal function tests (baseline and every 6-12 months), antinuclear antibodies (baseline and every 6-12 months); ophthalmic exam (pretreatment and yearly)
Dietary Considerations
To reduce nausea, oral drug can be administered with food or milk or in 2 divided doses 30 minutes apart. Avoid furocoumarin-containing foods (limes, figs, parsley, celery, cloves, lemon, mustard, carrots).
Patient Education
Do not take any new medication during therapy unless approved by prescriber. This medication is used in conjunction with specific ultraviolet treatment. Take as directed, with food or milk to reduce nausea. Consult prescriber for specific dietary instructions. Avoid use of any other skin treatments unless approved by prescriber. Control exposure to direct sunlight as per prescriber's instructions. If sunlight cannot be avoided, use sunblock (consult prescriber for specific SPF level); wear protective clothing and wraparound protective eyewear. Consult prescriber immediately if burning, blistering, or skin irritation occur. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause nervousness, dizziness, or depression
Mental Health: Effects on Psychiatric Treatment
Concurrent use with psychotropics may produce additive photosensitivity
Nursing: Physical Assessment/Monitoring
Note: This drug is administered in conjunction with ultraviolet light or ultraviolet radiation therapy. Teach patient proper use, side effects/appropriate interventions (eg, sunlight precautions), and adverse reactions to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule:
8-MOP®: 10 mg [hard-gelatin capsule]
Oxsoralen-Ultra®: 10 mg [soft-gelatin capsule]
Lotion:
Oxsoralen®: 1% (30 mL) [contains alcohol 71%]
Solution, for extracorporeal administration:
Uvadex®: 20 mcg/mL (10 mL) [not for injection]
Pricing: U.S. (www.drugstore.com)
Capsules (8-Mop)
10 mg (50): $1665.62
Capsules (Oxsoralen Ultra)
10 mg (30): $979.72
References
Stern RS, “Psoralen and Ultraviolet a Light Therapy for Psoriasis,” N Engl J Med, 2007, 357(7):682-90.
Stern RS, Nichols KT and Vateva LH, “Malignant Melanoma in Patients Treated for Psoriasis With Methoxsalen (Psoralen) and Ultraviolet A Radiation (PUVA). The PUVA Follow-Up Study,” N Engl J Med, 1997, 336(15):1041-5.
International Brand Names
Lexi-Comp.com
Last full review/revision December 2009
Content last modified December 2009
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