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    Photosensitizing Agents

    BOXED WARNING

    Chemotherapy, psoriasis, radiation therapy, requires an experienced clinician

    Administration of methoxsalen sterile solution (Uvadex) requires an experienced clinician who has special competence in the diagnosis and treatment of cutaneous T-cell lymphoma and who have special training and experience in the UVAR Photopheresis System; consult the UVAR Photopheresis System operator's manual before using this product. Methoxsalen with UV radiation should be used only by clinicians with special competence in the diagnosis and treatment of psoriasis and vitiligo and special training and experience in photochemotherapy. Use of psoralen and ultraviolet radiation therapy should be under constant supervision of such a clinician. For the treatment of psoriasis, photochemotherapy should be restricted to patients with severe, recalcitrant, disabling, psoriasis that has not responded adequately to other forms of therapy and only when the diagnosis is certain. Patients with erythrodermic psoriasis should be closely monitored because pre-existing erythema may obscure observations of possible treatment-related phototoxic erythema. Because of the possibility of ocular damage, aging of the skin, and cutaneous cancers, patients should be fully informed of the inherent risks of this therapy. When methoxsalen is used in combination with photopheresis, refer to the UVAR System Operator's Manual for specific warnings, cautions, indications, and instructions related to photopheresis.

    DEA CLASS

    Rx

    DESCRIPTION

    Naturally occurring photoactive psoralen or furocoumarin; hard gelatin and soft gelatin capsules have different bioavailabilities and onset of photosensitization; do not use interchangeably; topical psoralens more potent than oral.

    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 palliative treatment of the skin manifestations of cutaneous T-cell lymphoma (CTCL) (a.k.a. mycosis fungoides) in conjunction with photopheresis with the UVAR instrument in patients who have not been responsive to other forms of treatment.
    NOTE: Methoxsalen soft gelatin capsules and hard gelatin capsules are not interchangeable. Dose adjustments may be necessary (see Pharmacokinetics and Contraindications).
    NOTE: Consult the UVAR photopheresis system operator's manual before using this product.
    Extracorporeal dosage (UVADEX)
    Adults

    During photopheresis, 200 mcg of methoxsalen is injected directly into the photoactivation bag during the first buffy coat collection cycle. At the end of 6 cycles, a total of 740 ml (240 ml buffy coat, 300 ml plasma, and 200 ml normal saline priming fluid) is collected and mixed with the 200 mcg of methoxsalen in the photoactivation bag. After photoactivation, the cells are reinfused into the patient. Photopheresis is given on 2 consecutive days every 4 weeks for a minimum of 7 treatment cycles (six months). If during the fourth cycle of treatment the patient has an increased skin score from baseline, the frequency of photopheresis may be increased to 2 consecutive treatments every 2 weeks. If a 25% improvement in the skin score is noted after 4 consecutive weeks, then the regular treatment schedule may resume. Patients who are maintained on the accelerated treatment schedule may receive a maximum of 20 cycles. There is no clinical evidence of additional treatment benefit beyond 6 months or with a different schedule.

    Oral dosage (hard gelatin capsules, 8-MOP)
    Adults

    Initially, 0.6 mg/kg PO 2 hours before collection of the plasma and buffy coat. A methoxsalen blood concentration of at least 50 ng/ml 2 hours after ingestion of the capsules is needed. If the blood concentration is < 50 ng/ml, wait 24 hours after the initial dose and then administer 0.6 mg/kg plus 10 mg PO to try to achieve the recommended blood concentration. Establish and confirm methoxsalen blood concentrations by laboratory analysis before photopheresis treatment initiation.

    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

    Give Oxsoralen-Ultra with low-fat food or milk 1.5—2 hours before measured periods of high-intensity UVA exposure.
    Give MOP with food or milk 2 hours before measured periods of high-intensity UVA exposure.

    Oral Solid Formulations

    The methoxsalen soft gelatin capsules and hard gelatin capsules are not interchangable. Soft gelatin capsules produce significantly greater bioavailability and a quicker photosensitization onset time than hard gelatin capsules. Evaluate each patient by determining the minimum phototoxic dose and phototoxic peak time after drug administration before photochemotherapy onset with Oxsoralen-Ultra.

    Injectable Administration
    Other Injectable Administration

    Extracorporeal dosage (UVADEX)
    Consult photopheresis system operator's manual prior to use.
    Do not dilute; inject contents of vial into photopheresis sytem immediately after being drawn up into a syringe.
    Do not inject directly into patients.
    Immediately discard any solution that is not used during the procedure; vial is for single use only.
    Use only supplied procedural kits as the product can adsorb onto PVC and plastics.
    Immediately inject into photoactivation bag once drawn into plastic syringe; discard any product exposed to a plastic syringe for more than one 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

    Burns

    Methoxsalen soft gelatin capsules (Oxsoralen-Ultra) should not be used interchangeably with methoxsalen hard gelatin capsules (8-MOP). The soft gelatin capsules exhibit significantly greater bioavailability and earlier photosensitization onset time than previously available dosage forms. Serious burns from either UVA or sunlight, even through window glass, can result if the recommended dosage of the drug and/or exposure schedules are exceeded. Patients should be treated in accordance with the dosimetry specifically recommended for the soft gelatin capsules. Determine the minimum phototoxic dose and phototoxic peak time after drug administration before use of long wave UVA radiation with soft gelatin capsules. If improperly used, the lotion may cause severe burns; only a physician should apply the lotion to a patient under controlled conditions for light exposure and subsequent light shielding. Never dispense methoxsalen lotion to a patient.

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

    Methoxsalen is contraindicated for use by patients with an idiosyncratic reaction to psoralen compounds or with conditions associated with skin photosensitivity disorder because the drug increases photosensitivity potential. Such conditions include systemic lupus erythematosus (SLE), porphyria cutanea tarda, erythropoietic protoporphyria (EPP), variegate porphyria, xeroderma pigmentosum, albinism, hydroa vacciniforme, leukoderma of infectious origin, and polymorphous light eruption.

    Chemotherapy, psoriasis, radiation therapy, requires an experienced clinician

    Administration of methoxsalen sterile solution (Uvadex) requires an experienced clinician who has special competence in the diagnosis and treatment of cutaneous T-cell lymphoma and who have special training and experience in the UVAR Photopheresis System; consult the UVAR Photopheresis System operator's manual before using this product. Methoxsalen with UV radiation should be used only by clinicians with special competence in the diagnosis and treatment of psoriasis and vitiligo and special training and experience in photochemotherapy. Use of psoralen and ultraviolet radiation therapy should be under constant supervision of such a clinician. For the treatment of psoriasis, photochemotherapy should be restricted to patients with severe, recalcitrant, disabling, psoriasis that has not responded adequately to other forms of therapy and only when the diagnosis is certain. Patients with erythrodermic psoriasis should be closely monitored because pre-existing erythema may obscure observations of possible treatment-related phototoxic erythema. Because of the possibility of ocular damage, aging of the skin, and cutaneous cancers, patients should be fully informed of the inherent risks of this therapy. When methoxsalen is used in combination with photopheresis, refer to the UVAR System Operator's Manual for specific warnings, cautions, indications, and instructions related to photopheresis.

    Melanoma, skin cancer

    Methoxsalen is contraindicated in patients with a history of melanoma, current melanoma, or invasive cutaneous squamous cell carcinoma because the drug can act as a photocarcinogen. Methoxsalen can potentiate the incidence of skin cancer or premature aging of the skin. Patients with basal cell carcinoma or a history of this condition should be observed carefully during treatment with PUVA. In addition, fair skinned patients and those with a history of arsenic treatment, radiation therapy, cytotoxic chemotherapy treatment, or prolonged tar and ultraviolet light B (UVB) therapy are at an increased risk for developing skin cancer. Patients receiving PUVA have an increased risk for the development of skin cancers, including melanoma, squamous cell skin cancer, and basal cell skin cancer. The risk is particularly high for patients who have received > 250 PUVA treatments and in those whose treatment has spanned > 15 years. Some patients developed melanoma over 5 years after completing PUVA therapy. Patients who have received PUVA therapy should be monitored throughout their lives for the development of cutaneous malignancies.

    Hepatic disease

    Patients with hepatic disease or insufficiency should be treated cautiously with methoxsalen since hepatic biotransformation is necessary for renal drug elimination. Use caution in patients with hepatic impairment undergoing photopheresis with methoxsalen. Although systemic exposure to methoxsalen is low and it is unlikely that patients with severe hepatic impairment will be at greater risk than patients with normal hepatic function, the potential benefits of photopheresis treatment should be weighed against any possible risk.

    Aphakia

    Methoxsalen is contraindicated for use by patients with aphakia (lack of lenses) because of an increased risk of retinal damage.

    Pregnancy

    Methoxsalen injection is classified as FDA pregnancy risk category D; oral and topical methoxsalen are classified as FDA pregnancy risk category C. There are no adequate human studies on the potential adverse effects in the fetus. Doses of methoxsalen injection much higher than those used in humans on a body surface area basis caused significant fetal toxicity, including increased fetal mortality, increased resorptions, and decreased fetal weight. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while taking methoxsalen.

    Breast-feeding

    According to the manufacturer of methoxsalen injection, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of methoxsalen to the mother.The systemic absorption after topical use of methoxsalen is unknown; the manufacturer recommends caution if topical or oral methoxsalen is administered during breast-feeding. It is unknown if methoxsalen is distributed into breast milk. This drug should be used during breast-feeding only when clearly needed.

    Sunlight (UV) exposure

    Sunlight (UV) exposure even through window glass can result in serious burns following therapy with methoxsalen. If improperly used, methoxsalen lotion may cause severe burns; only a physician should apply the lotion to a patient under controlled conditions for light exposure and subsequent light shielding. Never dispense methoxsalen lotion to a patient. Patients should avoid sun exposure, even through window glass or cloud cover, for at least 8 hours after taking methoxsalen. If sun exposure cannot be avoided, patients should wear protective devices such as a hat and gloves and apply sunscreens that filter out UVA radiation (at least SPF 15). These sunscreens should be applied to all areas that might be exposed to sunlight, including lips. Sunscreens should not be applied to areas affected by psoriasis until after the patient has been treated in a UVA chamber. UVA-absorbing wrap-around sunglasses should be worn during daylight hours for 24 hours after combined methoxsalen/UVA therapy. Patients should not sunbathe 24 hours before and 48 hours after methoxsalen and UV therapy. The presence of a sunburn may prevent an accurate evaluation of the patient's response to photochemotherapy. The photosensitizing effects of methoxsalen lotion are greater than the oral capsules; counsel patients to keep treated areas protected. Also, methoxsalen soft gelatin capsules exhibit significantly greater bioavailability and earlier photosensitization onset time than previous methoxsalen dosage forms. Patients should be treated in accordance with the dosimetry specifically recommended for methoxsalen soft gelatin capsules. Determine the minimum phototoxic dose and phototoxic peak time after drug administration before use of long wave UVA radiation with methoxsalen soft gelatin capsules. Methoxsalen soft gelatin capsules (Oxsoralen-Ultra) should not be used interchangeably with methoxsalen hard gelatin capsules (8-MOP).

    Cataracts

    Because of the cataractogenic potential of psoralens and PUVA therapy, extreme caution should be exercised when using PUVA therapy in patients with cataracts. Animal studies have shown that cataracts develop without eye protection. Studies in humans have not shown an increased risk for cataract formation when the appropriate eye protection is used. UVA-absorbing wrap-around sunglasses should be worn during in daylight for 24 hours after combined methoxsalen/UVA therapy. Patients should have an ophthalmologic exam prior to start of therapy and then yearly.

    Cardiac disease

    If possible, patients with severe cardiac disease should not be treated in a vertical PUVA chamber, during combined methoxsalen/UVA therapy, due to the potential for heat stress or the consequences of prolonged standing.

    Children

    The safety of methoxsalen therapy in children has not been established, and the lotion is contraindicated for use by children because neither the safety nor efficacy of treatment have been established. Potential hazards of long-term PUVA therapy include the possibilities of carcinogenicity and cataract formation as well as actinic degeneration (premature aging of the skin).

    ADVERSE REACTIONS

    Moderate

    hypotension / Rapid / 1.0
    bullous rash / Early / Incidence not known
    cataracts / Delayed / Incidence not known
    secondary malignancy / 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 (unspecified) / 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.
    Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
    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.
    Sipuleucel-T: (Major) Concomitant use of sipuleucel-T and antineoplastic agents should be avoided. Concurrent administration of antineoplastic agents with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving antineoplastic agents may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of antineoplastic agents prior to initiating therapy with sipuleucel-T.
    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 injection is classified as FDA pregnancy risk category D; oral and topical methoxsalen are classified as FDA pregnancy risk category C. There are no adequate human studies on the potential adverse effects in the fetus. Doses of methoxsalen injection much higher than those used in humans on a body surface area basis caused significant fetal toxicity, including increased fetal mortality, increased resorptions, and decreased fetal weight. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while taking methoxsalen.

    According to the manufacturer of methoxsalen injection, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of methoxsalen to the mother.The systemic absorption after topical use of methoxsalen is unknown; the manufacturer recommends caution if topical or oral methoxsalen is administered during breast-feeding. It is unknown if methoxsalen is distributed into breast milk. This drug should be used during breast-feeding only when clearly needed.

    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.