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  • CLASSES

    Photosensitizing Agents

    BOXED WARNING

    Requires an experienced clinician

    Administration of methoxsalen for extracorporeal administration requires an experienced clinician who has special competence in the diagnosis and treatment of cutaneous T-cell lymphoma and who has special training and experience in the UVAR XTS or CELLEX photopheresis system; consult the operator's manual before using this product. Oral methoxsalen with UV radiation should be used only by clinicians trained in the diagnosis and treatment of psoriasis and vitiligo and who have experience in photochemotherapy.

    Melanoma, new primary malignancy, radiation therapy, skin cancer

    Oral methoxsalen is contraindicated in patients who have melanoma or a history of melanoma and in patients with invasive squamous cell carcinomas. Because pre-existing erythema may obscure observations of possible treatment-related phototoxic erythema, monitor patients with erythrodermic psoriasis closely. Methoxsalen therapy may cause a new primary malignancy such as skin cancer; monitor patients for the development of skin tumors. Additionally, patients with a history of basal cell carcinoma should be monitored closely. Previous cutaneous exposure to tar and UVB treatment, radiation therapy, or arsenic may increase the risk of developing skin carcinomas.

    DEA CLASS

    Rx

    DESCRIPTION

    Photosensitizing agent
    Used for the palliative treatment of the skin manifestations of cutaneous T-cell lymphoma in conjunction with photopheresis (as a solution for extracorporeal administration); soft gelatin capsules in conjunction with ultraviolet radiation used for the symptomatic control of psoriasis
    Patients should avoid UV or sunlight exposure during and for 24 hours after therapy

    COMMON BRAND NAMES

    8-MOP, Oxsoralen, Oxsoralen-Ultra, UVADEX

    HOW SUPPLIED

    Methoxsalen/Oxsoralen-Ultra Oral Cap: 10mg
    UVADEX Extracorporeal Sol: 1mL, 20mcg

    DOSAGE & INDICATIONS

    For the treatment of cutaneous T-cell lymphoma (CTCL).
    For the palliative treatment of the skin manifestations of CTCL unresponsive to other forms of treatment, used with the UVAR XTS or CELLEX photopheresis system.
    Extracorporeal dosage (Uvadex)
    Adults

    Calculate the dosage according to treatment volume as follows: treatment volume X 0.017 = mL of methoxsalen per treatment. Each treatment involves collection of leukocytes, photoactivation, and reinfusion of photoactivated cells; methoxsalen is injected into the recirculation bag prior to the photoactivation phase. Treatment is given on 2 consecutive days every 4 weeks for at least 7 treatment cycles (approximately 6 months). In patients who have an increased skin score (from baseline) at the fourth treatment assessment (at approximately 3 months), an accelerated treatment schedule may be administered consisting of 2 consecutive treatments every 2 weeks for a maximum of 20 cycles. Resume the regular treatment schedule if there is a 25% improvement in the skin score after 4 consecutive weeks on the accelerated treatment schedule. There is no clinical evidence of additional treatment benefit beyond 6 months or with a different schedule.

    For the treatment of idiopathic vitiligo (in conjunction with UVA).
    NOTE: Idiopathic vitiligo is reversible but not equally reversible in every patient. Repigmentation will vary in completeness, onset time, and duration. Repigmentation occurs more rapidly in fleshy areas such as the face, abdomen, and buttocks and less rapidly over less fleshy areas such as the dorsum of the hands or feet.
    Oral dosage (hard gelatin capsules, 8-MOP)
    Adults

    20 mg PO given with food or milk, 2—4 hours prior to measured periods of sunlight or UV radiation, 2—3 times weekly. Duration of exposure to sunlight or UVA is dependent upon number of exposures and basic skin color. Therapy should be on alternate days; never give on 2 consecutive days. Severe burns may result from doses greater than 0.6 mg/kg. This dosage should not be exceeded.

    Topical dosage
    Adults and Adolescents

    Apply to a well-defined area and then expose the area to UVA. Initial exposure time should be conservative and not exceed that which is predicted to be one-half the minimal erythema dose. Determine the treatment interval by the erythema response; generally once a week treatment or less is recommended. Pigmentation may begin after a few weeks, but significant repigmentation may require 6—9 months of treatment. Periodic retreatment may be necessary to retain all of the new pigment.

    For the treatment of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy and is diagnosed by biopsy; alopecia† areata; atopic dermatitis†; eczema†; lichen planus†; and for increased tolerance of skin to sunlight†.
    NOTE: Methoxsalen soft gelatin capsules and hard gelatin capsules are not interchangeable. The mean J/cm2 for the soft gelatin capsules is substantially less than that required for the hard gelatin capsules due to pharmacokinetic differences (see Pharmacokinetics). Evaluate each patient by determining the minimum phototoxic dose and phototoxic peak time after drug administration before photochemotherapy onset with Oxsoralen-Ultra.
    NOTE: In the event that the weight of a patient changes during treatment such that he/she falls into an adjacent weight range/dose category, no change in the methoxsalen dose is usually required. If, in the physician's opinion, however, a weight change is sufficiently great to modify the drug dose, then adjust the UVA exposure time.
    NOTE: If a patient's generalized psoriasis is not responding or if the condition appears to be worsening during treatment, consider the possibility of a generalized phototoxic reaction, which may be confirmed by the improvement of the condition following temporary discontinuance of this therapy for two weeks. If no improvement occurs during treatment interruption, this patient may be considered a treatment failure.
    NOTE: The number of doses per week of methoxsalen capsules will be determined by the patient's schedule of UVA exposures. The severity and extent of the patient's erythema may be used to determine whether the next exposure should be shortened, omitted, or maintained at the previous dosage.
    NOTE: If the patient flares during maintenance treatment (i.e., develops psoriasis on more than 5% of the originally involved areas of the body), his maintenance treatment schedule may be changed to the preceding maintenance or clearing schedule. The patient may be kept on his schedule until again 95% clear. If the original maintenance treatment schedule is unable to control the psoriasis, the schedule may be changed to a more frequent regimen.
    Oral dosage (hard gelatin capsules, 8-MOP or soft gelatin capsules, Oxsoralen-Ultra)
    Adults

    Administer the appropriate dose (as follows) with food or milk 2—3 times weekly; separate doses by at least 48 hours. For patients weighing < 30 kg administer 10 mg PO; for patients weighing 30—50 kg administer 20 mg PO; for patients weighing 51—65 kg administer 30 mg PO; for patients weighing 66—80 kg administer 40 mg PO; for patients weighing 81—90 kg administer 50 mg PO; for patients weighing 91—115 kg administer 60 mg PO; and for patients weighing > 115 kg administer 70 mg PO. Give Oxsoralen-Ultra 1.5—2 hours before or 8-MOP 2 hours before measured periods of high-intensity UVA exposure. If there is no response or only a minimal response after 15 treatments, the dosage of methoxsalen may be increased by 10 mg. The one-time increase in dosage may be continued for the remainder of the treatment course but should not be exceeded. When patients have achieved 95% clearing or a Grade 4 response (95% improvement with complete flattening of plaques including borders), they may be placed on a maintenance schedule. Once a week treatment, once every 2 weeks, once every 3 weeks, and then as necessary for flares is the recommended sequence. Adherence to each maintenance sequence step for at least 2 treatments is recommended unless erythema or psoriatic flare occurs.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    For vitiligo, 0.6 mg/kg PO qod; For psoriasis, 20 mg PO qod for patients < 30 kg, 30 mg PO qod for patients 30—50 kg, 40 mg PO qod for patients 51—65 kg, 50 mg PO qod for patients 66—80 kg, 60 mg PO qod for patients 81—90 kg, 70 mg PO qod for patients 91—115 kg, and 80 mg PO qod for patients > 115 kg for either hard gelatin capsules or soft gelatin capsules; Maximum dosage limits not established for topical therapy.

    Elderly

    For vitiligo, 0.6 mg/kg PO qod; For psoriasis, 20 mg PO qod for patients < 30 kg, 30 mg PO qod for patients 30—50 kg, 40 mg PO qod for patients 51—65 kg, 50 mg PO qod for patients 66—80 kg, 60 mg PO qod for patients 81—90 kg, 70 mg PO qod for patients 91—115 kg, and 80 mg PO qod for patients > 115 kg for either hard gelatin capsules or soft gelatin capsules; Maximum dosage limits not established for topical therapy.

    Adolescents

    Maximum dosage limits not established for topical therapy; systemic treatment is not recommended.

    Children

    Not recommended.

    Infants

    Not recommended.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines are not available; however, patients should be treated with caution, as methoxsalen undergoes significant hepatic metabolism.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. Although data are lacking in patients with varying degrees of renal impairment, no reduction of dose or prolongation of the time required to use UV light protection were reported in renal transplant recipients with poor renal function who have undergone photopheresis treatment with methoxsalen.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Take methoxsalen soft gelatin capsules with food or low-fat milk approximately 2 hours prior to ultraviolet light treatment.

    Injectable Administration
    Other Injectable Administration

    Extracorporeal dosage (Uvadex)
    Methoxsalen 20 mcg/mL solution is used in combination with the Therakos UVAR XTS and CELLEX photopheresis systems; consult the photopheresis system operator's manual prior to use.
    Each methoxsalen treatment involves collection of leukocytes, photoactivation, and reinfusion of photoactivated cells.
    Do NOT directly inject methoxsalen solution into patients.
    Preparation
    Do NOT dilute methoxsalen solution.
    Draw the appropriate amount/volume of methoxsalen solution for the treatment dose into a plastic syringe; immediately inject into the photoactivation bag.
    Methoxsalen solution may adsorb onto PVC and plastics; therefore, only use photopheresis procedural kits supplied for use with the instrument.
    Discard any solution that is not used during the procedure; vial is for single use only.
    Storage in a plastic syringe: discard contents if not used within 1 hour.

    Topical Administration
    Cream/Ointment/Lotion Formulations

    Only a physician should apply the lotion to a patient. Never dispense the lotion to a patient.
    To avoid photosensitization and possible burns, use a finger cot or rubber glove when applying the lotion to a patient.
    Lotion should only be applied by a physician to a small, well-defined area of vitiligo. Preferably, application of the lotion should only be to lesions that can be protected by clothing or a sunscreen from subsequent exposure to radiant UVA; suitable covering of the application area or topical sunblock application to the application area should follow the therapeutic UVA exposure. If the lotion is applied to the hands or face, instruct the patient to keep the treated areas protected from light by use of protective clothing or sunscreening agents. The application area may be highly photosensitive for several days. A severe burn injury may occur if the application area is exposed to additional UV or sunlight.

    STORAGE

    8-MOP:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Oxsoralen:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Oxsoralen-Ultra:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    UVADEX:
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Albinism, porphyria, skin photosensitivity disorder, systemic lupus erythematosus (SLE), xeroderma pigmentosum

    Methoxsalen is contraindicated in patients who have a history of a light sensitive disease/skin photosensitivity disorder such systemic lupus erythematosus (SLE), porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum, and albinism.

    Requires an experienced clinician

    Administration of methoxsalen for extracorporeal administration requires an experienced clinician who has special competence in the diagnosis and treatment of cutaneous T-cell lymphoma and who has special training and experience in the UVAR XTS or CELLEX photopheresis system; consult the operator's manual before using this product. Oral methoxsalen with UV radiation should be used only by clinicians trained in the diagnosis and treatment of psoriasis and vitiligo and who have experience in photochemotherapy.

    Melanoma, new primary malignancy, radiation therapy, skin cancer

    Oral methoxsalen is contraindicated in patients who have melanoma or a history of melanoma and in patients with invasive squamous cell carcinomas. Because pre-existing erythema may obscure observations of possible treatment-related phototoxic erythema, monitor patients with erythrodermic psoriasis closely. Methoxsalen therapy may cause a new primary malignancy such as skin cancer; monitor patients for the development of skin tumors. Additionally, patients with a history of basal cell carcinoma should be monitored closely. Previous cutaneous exposure to tar and UVB treatment, radiation therapy, or arsenic may increase the risk of developing skin carcinomas.

    Hepatic disease

    Use oral methoxsalen with caution in patients with hepatic disease or impairment; hepatic biotransformation is necessary for urinary excretion. Before starting therapy in patients with hepatic impairment, weigh the potential benefit of methoxsalen for extracorporeal administration with photopheresis against any possible risk of hepatic toxicity from low systemic exposure to methoxsalen.

    Aphakia, cataracts, ocular disease

    Ocular toxicity including cataracts may occur with methoxsalen therapy; therefore, use it with caution in patients with ocular disease. Methoxsalen is contraindicated in patients with aphakia who have a significantly increased risk of retinal damage due to the absence of lenses. Patients receiving oral methoxsalen should have an ophthalmologic exam prior to start of therapy and then yearly thereafter.

    Burns, sunlight (UV) exposure

    Serious burns and skin aging may occur due to sunlight (UV) exposure following methoxsalen administration. Patients should avoid sunlight or UV exposure (or sunscreen with SF 15 or higher) and wear protective UVA absorbing sunglasses for 24 hours after therapy. Patients who are receiving concomitant therapy with other topical or systemic photosensitizing agents have greater risk for photosensitivity reactions with methoxsalen therapy.

    Cardiac disease, geriatric

    Use oral methoxsalen with caution in patients with cardiac disease, patients unable to tolerate prolonged standing or exposure to heat stress, and geriatric patients with a history of cataracts, kidney/or liver dysfunction, or skin cancer.

    Pregnancy

    Methoxsalen may cause fetal harm if administered during pregnancy, based on data from animal studies. Methoxsalen soft gelatin capsules are listed as FDA pregnancy category C; methoxsalen for extracorporeal administration with photopheresis is listed as FDA pregnancy category D. Females of reproductive potential should avoid pregnancy during methoxsalen therapy. If methoxsalen is used during pregnancy or if pregnancy occurs during methoxsalen therapy, the woman should be apprised of the potential hazard to the fetus. Fetal toxicities (e.g., fetal death, decreased feal weight, and skeletal malformations/variations) were observed following administration of methoxsalen (80 to 160 mg/kg/day) in pregnant rats.

    Contraception requirements, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during methoxsalen treatment. Females of reproductive potential should avoid pregnancy and use effective contraception during methoxsalen therapy.

    Breast-feeding

    It is not known if methoxsalen is secreted in human milk. Due to the risk of serious adverse reactions in nursing infants, women should discontinue breast-feeding during methoxsalen therapy.

    ADVERSE REACTIONS

    Severe

    new primary malignancy / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    thromboembolism / Delayed / Incidence not known

    Moderate

    hypotension / Rapid / 1.0
    bullous rash / Early / Incidence not known
    cataracts / Delayed / Incidence not known
    erythema / Early / Incidence not known
    depression / Delayed / Incidence not known
    edema / Delayed / Incidence not known

    Mild

    nausea / Early / 0-10.0
    pruritus / Rapid / 10.0-10.0
    infection / Delayed / 10.0-10.0
    dysgeusia / Early / 0-1.0
    fever / Early / 0-1.0
    skin hypopigmentation / Delayed / Incidence not known
    folliculitis / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    rash / Early / Incidence not known
    vesicular rash / Delayed / Incidence not known
    miliaria / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    insomnia / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    headache / Early / Incidence not known
    malaise / Early / Incidence not known
    muscle cramps / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abciximab: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Acetohexamide: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Alefacept: (Severe) Patients receiving photodynamic therapy with methoxsalen should not receive concurrent therapy with alefacept; there is the possibility of excessive immunosuppression and subsequent risks of infection and other serious side effects. In clinical efficacy trials, concurrent treatment of alefacept with these types of agents did not occur. The duration of the period following treatment with alefacept that is appropriate before starting other immunosuppressive therapy has not been evaluated.
    Aliskiren; Amlodipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound. (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Allopurinol: (Minor) Preclinical data suggests that allopurinol may decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Alpha interferons: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Alteplase, tPA: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Amlodipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Amlodipine; Atorvastatin: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Amlodipine; Benazepril: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound. (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound. (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Amlodipine; Olmesartan: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Amlodipine; Telmisartan: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Amlodipine; Valsartan: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Anagrelide: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Anticoagulants: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Antithrombin III: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Apixaban: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Argatroban: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Aspirin, ASA; Dipyridamole: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Atenolol; Chlorthalidone: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Use methoxsalen and methylene blue together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Azelastine; Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Azilsartan; Chlorthalidone: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Beclomethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Bendroflumethiazide; Nadolol: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Use methoxsalen and methylene blue together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Betamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Betrixaban: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Bivalirudin: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Budesonide; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Calcium-channel blockers: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Chlorothiazide: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Chlorpromazine: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Chlorpropamide: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Chlorthalidone: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Chlorthalidone; Clonidine: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Ciclesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Cilostazol: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Clevidipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Clopidogrel: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Cod Liver Oil: (Major) Retinoids such as vitamin A found in cod liver oil are associated with photosensitivity. Concomitant administration of photosensitizing agents with retinoids can increase the incidence or severity of photosensitization.
    Codeine; Phenylephrine; Promethazine: (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet (UV) exposure.
    Codeine; Promethazine: (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet (UV) exposure.
    Corticosteroids: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Corticotropin, ACTH: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Cortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Dabigatran: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Dalteparin: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Danaparoid: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Deflazacort: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Demeclocycline: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Desirudin: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Dexamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Dextromethorphan; Promethazine: (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet (UV) exposure.
    Diclofenac: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as diclofenac could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of diclofenac before and during photodynamic therapy may be advisable.
    Diclofenac; Misoprostol: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as diclofenac could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of diclofenac before and during photodynamic therapy may be advisable.
    Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
    Diltiazem: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Diphenhydramine; Ibuprofen: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as ibuprofen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of ibuprofen before and during photodynamic therapy may be advisable.
    Diphenhydramine; Naproxen: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as naproxen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of naproxen before and during photodynamic therapy may be advisable.
    Dipyridamole: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Doxycycline: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Edoxaban: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Enalapril; Felodipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Enoxaparin: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Eptifibatide: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Esomeprazole; Naproxen: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as naproxen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of naproxen before and during photodynamic therapy may be advisable.
    Ethotoin: (Major) Hydantoins may increase the clearance of methoxsalen. The mechanism may be due to phenytoin induction of hepatic metabolizing enzymes resulting in reduced methoxsalen serum concentrations.
    Etodolac: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as etodolac could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of etodolac before and during photodynamic therapy may be advisable.
    Famotidine; Ibuprofen: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as ibuprofen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of ibuprofen before and during photodynamic therapy may be advisable.
    Felodipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Fenoprofen: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as fenoprofen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of fenoprofen before and during photodynamic therapy may be advisable.
    Fludrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Flunisolide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluphenazine: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Flurbiprofen: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as flurbirprofen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of flurbirprofen before and during photodynamic therapy may be advisable.
    Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluticasone; Salmeterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluticasone; Umeclidinium; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluticasone; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fondaparinux: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Food: (Minor) Phototoxic dermatitis can result from contact with psoralen-containing plants/foods such as celery, fennel, limes, parsley, and parsnip. Contact exposure to such foods should be approached with care during methoxsalen treatment as in theory such exposure might increase the likelyhood of a skin reaction. Follow all directions of the manufacturer to avoid untoward methoxsalen-induced photoreactions.
    Formoterol; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Fosphenytoin: (Major) Hydantoins may increase the clearance of methoxsalen. The mechanism may be due to phenytoin induction of hepatic metabolizing enzymes resulting in reduced methoxsalen serum concentrations.
    Glimepiride: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Glimepiride; Pioglitazone: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Glimepiride; Rosiglitazone: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Glipizide: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Glipizide; Metformin: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Glyburide: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Glyburide; Metformin: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Griseofulvin: (Moderate) Use methoxsalen and griseofulvin together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Heparin: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Hydantoins: (Major) Hydantoins may increase the clearance of methoxsalen. The mechanism may be due to phenytoin induction of hepatic metabolizing enzymes resulting in reduced methoxsalen serum concentrations.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Hydrocodone; Ibuprofen: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as ibuprofen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of ibuprofen before and during photodynamic therapy may be advisable.
    Hydrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Use methoxsalen and methylene blue together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Ibuprofen: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as ibuprofen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of ibuprofen before and during photodynamic therapy may be advisable.
    Ibuprofen; Oxycodone: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as ibuprofen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of ibuprofen before and during photodynamic therapy may be advisable.
    Ibuprofen; Pseudoephedrine: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as ibuprofen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of ibuprofen before and during photodynamic therapy may be advisable.
    Indapamide: (Moderate) Indapamide may cause photosensitivity and may increase the photosensitization effects of drugs like photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Indomethacin: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as indomethacin could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of indomethacin before and during photodynamic therapy may be advisable.
    Interferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Interferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Interferon Alfa-2b; Ribavirin: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Interferon Alfacon-1: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Interferon Alfa-n3: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Isradipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Ketoprofen: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as ketoprofen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of ketoprofen before and during photodynamic therapy may be advisable.
    Ketorolac: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as ketorolac could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of ketorolac before and during photodynamic therapy may be advisable.
    Lansoprazole; Naproxen: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as naproxen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of naproxen before and during photodynamic therapy may be advisable.
    Lepirudin: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Lesinurad; Allopurinol: (Minor) Preclinical data suggests that allopurinol may decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Meclofenamate Sodium: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as meclofenamate could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of meclofenamate before and during photodynamic therapy may be advisable.
    Mefenamic Acid: (Major) Preclinical data suggest agents that inhibit prostaglandin synthesis such as mefenamic acid could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of mefenamic acid before and during photodynamic therapy may be advisable.
    Melatonin: (Major) Caution should be exercised in patients on methoxsalen therapy (5- or 8-methoxypsoralen or 5-MOP and 8-MOP), which increases melatonin levels by inhibiting its metabolism. Methoxsalen is a potent CYP1A2 inhibitor in vitro.
    Meloxicam: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as meloxicam could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Meperidine; Promethazine: (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet (UV) exposure.
    Mesoridazine: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Use methoxsalen and methylene blue together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Methotrexate: (Major) Methotrexate may increase the photosensitizing effects of photosensitizing agents used for photodynamic therapy.
    Methyclothiazide: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Methylene Blue: (Moderate) Use methoxsalen and methylene blue together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Methylprednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Metolazone: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Minocycline: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Nabumetone: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as nabumetone could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of nabumetone before and during photodynamic therapy may be advisable.
    Naproxen: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as naproxen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of naproxen before and during photodynamic therapy may be advisable.
    Naproxen; Pseudoephedrine: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as naproxen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of naproxen before and during photodynamic therapy may be advisable.
    Naproxen; Sumatriptan: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as naproxen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of naproxen before and during photodynamic therapy may be advisable.
    Nicardipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Nifedipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Nimodipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Nisoldipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Oxaprozin: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as oxaprozin could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of oxaprozin before and during photodynamic therapy may be advisable.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Peginterferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Peginterferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Pentosan: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Perindopril; Amlodipine: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Perphenazine: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Perphenazine; Amitriptyline: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Phenothiazines: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Phenylephrine; Promethazine: (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet (UV) exposure.
    Phenytoin: (Major) Hydantoins may increase the clearance of methoxsalen. The mechanism may be due to phenytoin induction of hepatic metabolizing enzymes resulting in reduced methoxsalen serum concentrations.
    Piroxicam: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as piroxicam could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of piroxicam before and during photodynamic therapy may be advisable.
    Platelet Inhibitors: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Prasugrel: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Prednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Prednisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Prochlorperazine: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Promethazine: (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet (UV) exposure.
    Reteplase, r-PA: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Retinoids: (Moderate) Use methoxsalen and retinoids together with caution; the risk of severe burns/phototoxicity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Rivaroxaban: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Rofecoxib: (Minor) Based on preclinical data, some agents that inhibit prostaglandin synthesis such as NSAIDs could decrease the efficacy of photodynamic therapy (PDT). It is not clear that all agents in these classes, including non-selective and COX-2 selective NSAID agents, would interact or if the preclinical data would hold true for human use. Furthermore, it is possible that the presence of an interaction could depend on the pathology of the underlying disease and the indication for which PDT is being used. Until further data are available in humans, consider the risk:benefit to continuing NSAID use during PDT treatments. Methoxsalen is a photosensitizing agent and concomitant administration of other photosensitizing agents may enhance the photosensitizing effects. Some NSAIDs are photosensitizing. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing on exposed skin. Follow all directions of the manufacturer to avoid untoward methoxsalen-induced photoreactions.
    St. John's Wort, Hypericum perforatum: (Major) St. John's wort has been reported to increase the phototoxicity associated with photosensitizing agents used in photodynamic therapy. Although interactions have not been reported, in theory it is possible that additive photosensitizing effects may result from the concomitant use of St. John's wort with other photosensitizing drugs.
    Streptokinase: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Sulfacetamide: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
    Sulfacetamide; Sulfur: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
    Sulfonamides: (Moderate) Use methoxsalen and sulfonamides together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Sulfonylureas: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Sulindac: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as sulindac could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of sulindac before and during photodynamic therapy may be advisable.
    Tenecteplase, TNK-tPA: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Tetracycline: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Tetracyclines: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Thiazide diuretics: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
    Thiethylperazine: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Thioridazine: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Thrombolytic Agents: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Ticagrelor: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Ticlopidine: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Tinzaparin: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Tirofiban: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Tolazamide: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Tolbutamide: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Tolmetin: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as tolmetin could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of tolmetin before and during photodynamic therapy may be advisable.
    Trandolapril; Verapamil: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Triamcinolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Trifluoperazine: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Urokinase: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Valdecoxib: (Minor) Based on preclinical data, some agents that inhibit prostaglandin synthesis such as NSAIDs could decrease the efficacy of photodynamic therapy (PDT). It is not clear that all agents in these classes, including non-selective and COX-2 selective NSAID agents, would interact or if the preclinical data would hold true for human use. Furthermore, it is possible that the presence of an interaction could depend on the pathology of the underlying disease and the indication for which PDT is being used. Until further data are available in humans, consider the risk:benefit to continuing NSAID use during PDT treatments. Methoxsalen is a photosensitizing agent and concomitant administration of other photosensitizing agents may enhance the photosensitizing effects. Some NSAIDs are photosensitizing. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing on exposed skin. Follow all directions of the manufacturer to avoid untoward methoxsalen-induced photoreactions.
    Verapamil: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Vorapaxar: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Warfarin: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Ziprasidone: (Moderate) Medications that may cause additive photosensitization when used with ziprasidone include methoxsalen. Patients should limit sunlight and ultra-violet exposure whenever possible, and use proper UV precautions to protect the skin.

    PREGNANCY AND LACTATION

    Pregnancy

    Methoxsalen may cause fetal harm if administered during pregnancy, based on data from animal studies. Methoxsalen soft gelatin capsules are listed as FDA pregnancy category C; methoxsalen for extracorporeal administration with photopheresis is listed as FDA pregnancy category D. Females of reproductive potential should avoid pregnancy during methoxsalen therapy. If methoxsalen is used during pregnancy or if pregnancy occurs during methoxsalen therapy, the woman should be apprised of the potential hazard to the fetus. Fetal toxicities (e.g., fetal death, decreased feal weight, and skeletal malformations/variations) were observed following administration of methoxsalen (80 to 160 mg/kg/day) in pregnant rats.

    It is not known if methoxsalen is secreted in human milk. Due to the risk of serious adverse reactions in nursing infants, women should discontinue breast-feeding during methoxsalen therapy.

    MECHANISM OF ACTION

    Mechanism of Action: When methoxsalen (psoralen, P) is activated by long wavelength ultraviolet radiation (UVA), it is a potent erythemogenic, melanogenic, and cytotoxic therapy. The strongest activity occurs in the UVA range of 320—400 nm. Skin reactivity to UVA (320—400 nm) radiation is markedly enhanced by the presence of methoxsalen. The exact mechanism of action of methoxsalen with epidermal melanocytes and keratinocytes is not known. The reaction of methoxsalen with DNA is better understood. Upon photoactivation, methoxsalen conjugates with DNA and forms monofunctional (binding to a single strand) and bifunctional (cross-linking of psoralen to both strands) adducts. In addition, reactions with proteins may occur. Methoxsalen also acts as a photosensitizer. Exposure to UVA in the presence of methoxsalen can lead to cell injury and inflammation. The usual manifestation of this reaction is delayed erythema, which may not be seen for several hours and peaks 48—72 hours. The inflammation is followed over several weeks by repair that is characterized by increased melanization of the epidermis and thickening of the stratum corneum.In the treatment of vitiligo, it has been suggested that melanocytes in the hair follicle are stimulated to move up the follicle and repopulate the epidermis. In the treatment of psoriasis or T-cell lymphoma, the mechanism is most often assumed to be DNA photo damage and result decrease in cell proliferation but other vascular, leukocyte, or cell regulatory mechanisms may also play a role.

    PHARMACOKINETICS

    Methoxsalen is administered orally, topically, and extracorporeally. Methoxsalen is reversibly bound to serum albumin and is also preferentially taken up by epidermal cells. Methoxsalen is almost completely metabolized in the liver. Approximately 95% of the drug is excreted as metabolites within 24 hours.

    Oral Route

    The absorption of methoxsalen from the GI tract following oral administration is variable. Administration with food or milk increases absorption. Administration should remain consistent with food intake because the observed photosensitizing effect is likely related to the serum concentration of the drug. There is wide (6—15 fold) interpatient variability in peak serum concentrations after oral doses of methoxsalen. Maximum plasma concentrations occur 1.5—3 hours after oral administration of the hard-gelatin capsules (8-MOP) and may last up to 8 hours. Peak drug concentrations of the soft-gelatin capsules (Oxsoralen-Ultra) are obtained between 0.5—4 hours (mean 1.8 hours) following administration with 8 oz of milk. The overall extent of drug absorption is approximately 2-fold higher for soft-gelatin capsules as compared to the hard-gelatin capsules. Detectable methoxsalen concentrations were observed for up to 12 hours after a dose of the soft-gelatin capsules. Photosensitivity studies demonstrate a shortened time of peak photosensitivity (1.5—2.1 hours) for soft-gelatin vs hard-gelatin capsules (3.9—4.25 hours). In addition, the mean minimal erythema dose (MED, J/cm2) for soft-gelatin capsules is substantially less than that for hard-gelatin capsules. The half-life methoxsalen is approximately 2 hours.

    Topical Route

    The extent of absorption of topical methoxsalen is not known. Peak photosensitivity following topical administration occurs within 1—2 hours and can persist for several days.

    Other Route(s)

    Extracorporeal Route
    Drug concentrations in the lens of the eye are comparable to serum concentrations. In an attempt to diminish interpatient variability and to increase exposure of white blood cells to the drug, methoxsalen sterile solution is injected directly into the buffy coat solution during photopheresis. This also results in a lower total dose of methoxsalen as compared to oral administration.