Version May 2024
Capsule: Only physicians who have special competence in the diagnosis and treatment of psoriasis 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 (photopheresis): Only physicians who have special competence in the diagnosis and treatment of cutaneous T-cell lymphoma and have special training and experience in the THERAKOS CELLEX photopheresis system should use methoxsalen. Consult the CELLEX Operator's Manual before using this product.
Methoxsalen soft gelatin capsules: This new dosage form of methoxsalen exhibits 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.
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 THERAKOS CELLEX photopheresis system (consult user's guide).
Treatment schedule: Two consecutive days every 4 weeks for a minimum of 7 treatment cycles (6 months), may accelerate to 2 consecutive days every 2 weeks if skin score worsens (eg, increases from baseline) after assessment during the fourth treatment cycle (~3 months). 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.
Psoriasis: Oral (soft gelatin capsule):
Initial: 0.4 mg/kg administered with food 75 to 90 minutes before exposure to UVA light; dose may be repeated 2 to 3 times per week until psoriasis is clear or almost clear; minimum interval between each session is 48 hours (Ref). Note: Round dosage to the nearest 10 mg capsule. Refer to treatment protocols for UVA exposure guidelines.
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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in manufacturer's labeling.
There are no dosage adjustments provided in manufacturer's labeling; use with caution.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse drug reactions may be reported with concomitant UVA light therapy.
>10%: Dermatologic: Hyperkeratosis (depigmented vitiliginous areas: 12%, including actinic keratosis, keratotic papules, lichenoid porokeratotic-like papules, and non-scaling dome-shaped papules)
1% to 10%:
Dermatologic: Pruritus (10%, can be severe)
Gastrointestinal: Nausea (10%)
Frequency not defined:
Dermatologic: Burning sensation of skin, dermatological disorder (premature aging), erythema of skin, malignant melanoma, skin photosensitivity, squamous cell carcinoma of skin
Ophthalmic: Cataract
Postmarketing:
Cardiovascular: Edema, hypotension
Dermatologic: Bulla, exacerbation of psoriasis, folliculitis, hypopigmentation, miliaria, skin rash, skin tenderness, skin vesicle, urticaria
Gastrointestinal: Dysgeusia, gastrointestinal distress
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Infection: Herpes simplex infection
Nervous system: Depression, dizziness, headache, insomnia, malaise, nervousness
Neuromuscular & skeletal: Lower limb cramp
Miscellaneous: Fever
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 (oral only); aphakia; melanoma or history of melanoma (oral only).
Additional contraindications for extracorporeal photopheresis: Contraindications to the photopheresis procedure; history of heparin-induced thrombocytopenia or low hematocrit, pregnancy (Knobler 2020).
Additional contraindications for Canadian labeling (Uvadex) ( not in US labeling): Severe cardiac disease; severe anemia; WBC >25,000/mm3; previous splenectomy and coagulation disorders; basal cell cancer; coexisting melanoma; squamous cell carcinoma.
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. Avoid direct and indirect sunlight for 24 hours after treatment.
• 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.
• Thromboembolic events: Have been reported, including pulmonary embolism and deep vein thrombosis in patients with graft-versus-host disease (methoxsalen is not FDA-approved for treatment of graft-versus-host disease).
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).
• Hepatic impairment: Methoxsalen undergoes hepatic metabolism; use with caution in patients with hepatic impairment.
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:
• Methoxsalen soft gelatin capsules: This new dosage form of methoxsalen exhibits significantly greater bioavailability and earlier onset of photosensitization compared to previous methoxsalen dosage forms (hard gelatin capsules).
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 THERAKOS 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).
• Experienced physician: Should be administered under the supervision of an experienced physician with special competence in the diagnosis and treatment of psoriasis (oral) or cutaneous T-cell lymphoma (injection [photopheresis]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Oxsoralen Ultra: 10 mg [DSC] [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, Extracorporeal:
Uvadex: 20 mcg/mL (10 mL) [contains alcohol, usp, propylene glycol]
May be product dependent
Capsules (Methoxsalen Rapid Oral)
10 mg (per each): $83.45
Solution (Uvadex Extracorporeal)
20 mcg/mL (per mL): $75.72
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection:
Uvadex: 20 mcg/mL (10ml) [contains ALCOHOL, USP, PROPYLENE GLYCOL]
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 photopheresis system immediately after being drawn up into a syringe. Refer to institution-specific protocols.
Oral: Symptomatic control of severe, recalcitrant disabling psoriasis in conjunction with UVA radiation referred to as PUVA (psoralen [eg, methoxsalen] plus UVA photochemotherapy).
Extracorporeal photopheresis: Palliative treatment of skin manifestations of cutaneous T-cell lymphoma (eg, Sezary Syndrome, mycosis fungoides) that is unresponsive to other forms of treatment.
Substrate of CYP2A6 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (moderate), CYP2A6 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agomelatine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Agomelatine. Risk C: Monitor therapy
Alosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Alosetron. Management: Avoid concomitant use of alosetron and moderate CYP1A2 inhibitors whenever possible. If combined use is necessary, monitor for increased alosetron effects/toxicities. Risk D: Consider therapy modification
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Anagrelide: CYP1A2 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Anagrelide. CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Anagrelide. Risk C: Monitor therapy
Bendamustine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bendamustine. Management: Consider alternatives to moderate CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Risk D: Consider therapy modification
Bromazepam: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bromazepam. Risk C: Monitor therapy
Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
DULoxetine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of DULoxetine. Risk C: Monitor therapy
Fezolinetant: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Melatonin: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Melatonin. Risk C: Monitor therapy
Methylene Blue: May enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
OLANZapine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of OLANZapine. Risk C: Monitor therapy
Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy
Photosensitizing Agents: May enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and moderate CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 1,602 mg per day (534 mg three times daily) and monitor for increased pirfenidone toxicities. Risk D: Consider therapy modification
Pomalidomide: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pomalidomide. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Propranolol: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Risk C: Monitor therapy
Ramelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramelteon. Risk C: Monitor therapy
Ramosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramosetron. Risk C: Monitor therapy
Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking moderate CYP1A2 inhibitors. Risk D: Consider therapy modification
ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy
ROPivacaine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPivacaine. Risk C: Monitor therapy
Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Tasimelteon. Risk C: Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, monitor for increased theophylline serum concentrations and toxicities when combined. Theophylline dose reductions will likely be required. Risk D: Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of TiZANidine. Management: If combined use cannot be avoided, initiate tizanidine in adults at 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
Methoxsalen serum concentrations may be increased if taken with food. Nausea can occur upon administration. Management: Capsules should be taken with food or milk. Avoid furocoumarin-containing foods (limes, figs, parsley, celery, cloves, lemon, mustard, carrots).
Women of childbearing potential should be advised to avoid pregnancy.
Adverse events were observed in animal reproduction studies.
It is not known if methoxsalen (systemic) is excreted in breast milk. The manufacturer recommends that caution be exercised when administering methoxsalen (systemic) to nursing women.
To reduce nausea, capsules should be taken with food or milk. Avoid furocoumarin-containing foods (limes, figs, parsley, celery, cloves, lemon, mustard, carrots).
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
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.
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); exposure using Uvadex is ~200 times less than with oral methoxsalen administration
Time to peak, serum:
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
Excretion: Urine (~95% as metabolites)
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