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Methoxsalen (Systemic)

Pronunciation

(meth OKS a len)

Index Terms

  • 8-Methoxypsoralen
  • 8-MOP
  • Methoxypsoralen

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

8-Mop: 10 mg [DSC]

Oxsoralen Ultra: 10 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow), methylparaben, propylparaben]

Generic: 10 mg

Solution, Injection:

Uvadex: 20 mcg/mL (10 mL) [contains alcohol, usp, propylene glycol]

Brand Names: U.S.

  • 8-Mop [DSC]
  • Oxsoralen Ultra
  • Uvadex

Pharmacologic Category

  • Psoralen

Pharmacology

Bonds covalently to pyrimidine bases in DNA, inhibits the synthesis of DNA, and suppresses cell division and epidermal turnover. 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.

Metabolism

Hepatic; forms metabolites

Excretion

Urine (~95% as metabolites)

Time to Peak

Hard-gelatin capsules (8-MOP): 1.5 to 6 hours (peak photosensitivity: ~4 hours)

Soft-gelatin capsules (Oxsoralen Ultra): 0.5 to 4 hours (peak photosensitivity: 1.5 to 2 hours)

Half-Life Elimination

~2 hours

Protein Binding

Reversibly bound to albumin

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)

Extracorporeal: Palliative treatment of skin manifestations of CTCL that is unresponsive to other forms of treatment

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 (8-MOP and Oxsoralen Ultra only); aphakia; melanoma or history of melanoma (8-MOP and Oxsoralen Ultra only); contraindications to the photopheresis procedure

Canadian labeling (Uvadex): Additional contraindications (not in U.S. labeling): Severe cardiac disease; severe anemia; WBC >25,000/mm3; previous splenectomy and coagulation disorders; basal cell cancer; coexisting melanoma; squamous cell carcinoma

Dosing: Adult

Note: Refer to treatment protocols for UVA exposure guidelines.

Psoriasis: Oral:

Initial: 10 to 70 mg 1.5 to 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 to 50 kg: 20 mg

51 to 65 kg: 30 mg

66 to 80 kg: 40 mg

81 to 90 kg: 50 mg

91 to 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 to 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

Cutaneous T-cell lymphoma (CTCL): Extracorporeal (Uvadex): Dose is determined by treatment volume; amount of Uvadex needed for each treatment may be calculated using the following equation: Treatment volume x 0.017 = mL of Uvadex needed. Inject this amount into the recirculation bag prior to the photoactivation phase using the UVAR XTS or CELLEX photopheresis system (consult user's guide).

Treatment schedule: Two consecutive days every 4 weeks for a minimum of 7 treatment cycles, may accelerate to 2 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. Patients maintained on accelerated therapy may receive a maximum of 20 accelerated therapy cycles. There is no clinical evidence to show that treatment with methoxsalen for more than 6 months or using a different schedule provides additional benefit.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling; use with caution.

Reconstitution

Solution should not be diluted. Vial contents should be injected into the photopheresis system immediately after being drawn up into a syringe. For single use only; discard unused portion immediately. Solution exposed to a plastic syringe for >1 hour should be discarded.

Administration

Oral: To reduce nausea, capsules should be administered with food or milk.

Extracorporeal: Do not inject solution directly into patients. Vial contents should be injected into the photoactivation bag of the UVAR XTS or CELLEX Photopheresis System immediately after being drawn up into a syringe. Solution can adsorb onto PVC and plastics; only UVAR XTS or CELLEX photopheresis procedural kits supplied for use with the instrument should be used to administer the product.

Dietary Considerations

To reduce nausea, capsules should be taken with food or milk. Avoid furocoumarin-containing foods (limes, figs, parsley, celery, cloves, lemon, mustard, carrots).

Storage

Capsules: Store at 25°C (77°F).

Injection: Store between 15°C and 30°C (59°F to 86°F).

Drug Interactions

Agomelatine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Agomelatine. Avoid combination

Artesunate: CYP2A6 Inhibitors may decrease serum concentrations of the active metabolite(s) of Artesunate. CYP2A6 Inhibitors may increase the serum concentration of Artesunate. Avoid combination

Bendamustine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Bendamustine. Concentrations of the active metabolites of bendamustine may be decreased. Monitor therapy

CloZAPine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Management: Reduce the dose of clozapine to one-third of the original dose when adding a strong CYP1A2 inhibitor, and monitor patient response closely. Return to the original clozapine dose when the strong CYP1A2 inhibitor is removed. Consider therapy modification

CYP1A2 Substrates: CYP1A2 Inhibitors (Strong) may decrease the metabolism of CYP1A2 Substrates. Consider therapy modification

CYP2A6 Substrates: CYP2A6 Inhibitors (Strong) may decrease the metabolism of CYP2A6 Substrates. Consider therapy modification

DULoxetine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of DULoxetine. Avoid combination

Pentoxifylline: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pentoxifylline. Monitor therapy

Pirfenidone: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pirfenidone. Management: See full monograph for specific recommendations. Canadian product labeling specifically lists the use of pirfenidone with fluvoxamine as contraindicated. Consider therapy modification

Pomalidomide: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pomalidomide. Management: Avoid when possible. Monitor toxicity closely when combined. In patients also receiving a P-gp inhibitor and strong CYP3A4 inhibitor, reduce pomalidomide dose by 50% (Canadian labeling says to reduce dose with any use of a strong CYP1A2 inhibitor). Avoid combination

Rasagiline: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking strong CYP1A2 inhibitors. Consider therapy modification

Tasimelteon: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Avoid combination

Tegafur: CYP2A6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tegafur. Specifically, CYP2A6 inhibitors may inhibit the conversion of tegafur into its active metabolite, 5-fluorouracil. Avoid combination

TiZANidine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of TiZANidine. Management: Tizanidine use with ciprofloxacin or fluvoxamine is contraindicated. If use with another strong inhibitor cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on response. Monitor closely. Avoid combination

Adverse Reactions

1% to 10%:

Dermatologic: Pruritus (10%)

Gastrointestinal: Nausea (10%)

Frequency not defined:

Cardiovascular: Edema, hypotension (due to photopheresis)

Central nervous system: Depression, dizziness, headache, insomnia, malaise, nervousness, vertigo

Dermatologic: Bulla, burning sensation of skin, dermatological disease (premature aging), ephelis, erythema, exfoliation of skin, folliculitis, hypopigmentation, miliaria, skin blister (painful), skin neoplasm, skin rash, skin tenderness, skin vesicle, urticaria

Infection: Infection (due to vascular access for photopheresis)

Ophthalmic: Cataract

ALERT: U.S. Boxed Warning

Experienced physician:

Capsule: Only health care providers who have special competence in the diagnosis and treatment of psoriasis and vitiligo (8-MOP only) and who have special training and experience in photochemotherapy should use methoxsalen with ultraviolet (UV) radiation. The use of psoralen and UV radiation therapy should be under constant supervision of such a health care provider. For the treatment of patients with psoriasis, restrict photochemotherapy to patients with severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy, and only when the diagnosis is certain. Because of the possibility of ocular damage, skin aging, and skin cancer (including melanoma), fully inform the patient of the risks inherent in this therapy.

Injection (photophoresis): Only health care providers who have special competence in the diagnosis and treatment of cutaneous T-cell lymphoma and have special training and experience in the UVAR XTS or CELLEX photopheresis system should use methoxsalen. Consult the appropriate operator's manual before using this product.

Product interchange (capsule):

Do not use Oxsoralen-Ultra (methoxsalen soft gelatin capsules) interchangeably with 8-MOP (methoxsalen hard gelatin capsules). Oxsoralen-Ultra soft gelatin capsules exhibit significantly greater bioavailability and earlier photosensitization onset time than previous methoxsalen dosage forms. Treat patients in accordance with the dosimetry specifically recommended for this product. Determine the minimum phototoxic dose and phototoxic peak time after drug administration prior to the onset of photochemotherapy with this dosage form.

8-MOP capsules may not be interchanged with Oxsoralen-Ultra capsules without retitration of the patient.

Warnings/Precautions

Concerns related to adverse effects:

• Actinic degeneration: Exposure to sunlight and/or ultraviolet radiation may result in premature aging of the skin.

• 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 after methoxsalen exposure to prevent possible formation of cataracts.

• Photosensitivity: Avoid sun (including sun lamp) exposure for 24 hours after methoxsalen ingestion or administration. 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. Canadian labeling contraindicates use in patients with basal cell cancer.

• 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). Canadian labeling contraindicates use in patients with severe cardiac disease.

• Hepatic impairment: Methoxsalen undergoes hepatic metabolism; use with caution in patients with hepatic impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Use caution with other (systemic or topical) photosensitizing drugs (eg, thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides, nalidixic acid, halogenated salicylanilides, anthralin, coal tar preparations).

Special populations:

• Pediatric: Safety and efficacy have not been established in children for cutaneous T-cell lymphoma (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) 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:

• Appropriate use: CTCL: 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 XTS or CELLEX photopheresis system.

• Appropriate use: Psoriasis: 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).

• Appropriate use: Vitiligo: Used in conjunction with controlled doses of long wave ultraviolet radiation or sunlight.

• 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.

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); signs/symptoms of skin cancer, burns, and photosensitivity

Pregnancy Risk Factor

C/D (Uvadex)

Pregnancy Considerations

Fetal toxicity has been observed in animal studies. Use during pregnancy is not recommended. Women of childbearing potential should be advised to avoid pregnancy. The Canadian labeling also recommends that male patients use effective contraception during and after photopheresis therapy.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, anxiety, or insomnia. Have patient report immediately to prescriber vision changes, severe skin irritation, sunburn, mole changes, skin growths, depression, severe dizziness, passing out, or edema (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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