Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

PSORALENS

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Psoralens are photosensitizing agents. Methoxsalen and trioxsalen are used in combination with ultraviolet light in the treatment of various skin conditions to enhance repigmentation. Psoralens are also present in numerous plants, foods, cosmetics, and perfumes.

Specific Substances

    A) Bergamot Oil
    1) Oleum Berganottae
    2) Bergamot Essence
    3) Oil of Bergamot
    Bergaten
    1) Bergaptan
    2) Bergaptene
    3) Heraclin
    4) Majudin
    5) 4-Methoxy-7H-furo(3,2-g)(1)benzopyran-7-one
    6) 5-Methoxypsoralen
    7) 5-MOP
    8) CAS 484-20-8
    3-Carbethoxypsoralen
    1) 3-CPS
    Methoxsalen
    1) Ammoidin
    2) 7H-furo(3,2-g)(1)benzopyran-7-one
    3) 6-Hydroxy-7-methoxy-5-benzofuranacrylic
    4) acid-g-lactone
    5) 8-Methoxy(furano-3',2':6,7-coumarin)
    6) 9-Methoxy-7H-furo(3,2-g)(1)benzopyran-7-one
    7) 8-Methoxy-4',5':6,7-furocoumarin
    8) 8-Methoxypsoralen
    9) 9-Methoxypsoralen
    10) Metoxaleno
    11) 8-MOP
    12) 8-MP
    13) Xanthotoxin
    14) CAS 298-81-7
    Trioxsalen
    1) TMP
    2) 2,5,9-Trimethyl-7H-furo(3,2,g)-chromen-7-one
    3) 4,5',8-Trimethylpsoralen
    4) CAS 3902-71-4

Available Forms Sources

    A) FORMS
    1) Methoxsalen is available as 10 mg liquid-filled capsules, 10 mg oral capsules, 1% topical lotion, and 20 mcg/mL sterile solution for injection (Prod Info UVADEX(R) intravenous injection solution, 2013; Prod Info 8-MOP(R) oral capsules, 2003; Prod Info UVADEX(R) photopheresis solution, 1999).
    B) SOURCES
    1) PLANT SOURCES
    a) Psorlens are found in over 30 plants in the Rutaceae, Umbelliferae, and Compositae families, as well as synthesized commercially.
    b) 8-MOP, methoxsalen, is obtained from Ammi majus or manufactured synthetically.
    c) Bergamot oil is obtained by expression from the fresh peel of the fruit of citrus bergamia (Rutaceae). Linalyl acetate and 5-methoxypsoralen are constituents of the oil.
    d) Diseased celery plants have been shown to have over 200 times the amount of psoralen as that found in healthy plants (Ashwood-Smith et al, 1985).
    e) Although not yet shown clinically, the chance of potentiating the clinical effects of psoralen drugs with naturally occurring furocoumarins exists.
    2) FOOD SOURCES
    a) Common foods containing furocoumarin, a photosensitizing substance which can occur in some plants, include: figs, parsley, parsnips, celery, wild carrots, limes, and mustard (Grant, 1986).
    b) The most frequent exposures in the United States are from the canning of carrots, celery and Persian limes, and from bergamot oil containing perfumes and sun tanning preparations.
    3) HERBAL PRODUCTS
    a) Fructus psoraleae, the seeds of the Psoralea corylifolia (Babchi), have been used in proprietary herbal products in China. Several cases of transient acute hepatitis in adults have been reported with the use of these products (Cheung et al, 2009). Hepatotoxicity also developed in a patient after the use of Psoralea corylifolia to treat vitiligo (Quayson et al, 2015).
    C) USES
    1) Methoxsalen is used to treat psoriasis and vitiligo. It is also used as a palliative treatment of the skin manifestations of cutaneous T-Cell lymphoma (CTCL) (Prod Info UVADEX(R) intravenous injection solution, 2013; Prod Info 8-MOP(R) oral capsules, 2003; Prod Info UVADEX(R) photopheresis solution, 1999).
    2) ACCEPTABLE DAILY INTAKE
    a) An estimated acceptable daily intake established for citral, geranyl acetate, citronellol, linalol, and linalyl acetate, expressed as citral, is up to 500 micrograms/kg body weight (JEF Reynolds , 2000).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Psoralens are photosensitizing agents, used in combination with ultraviolet light (PUVA therapy) in the treatment of various skin conditions to enhance repigmentation. Methoxsalen is used to treat psoriasis and vitiligo. It is also used as a palliative treatment of the skin manifestations of cutaneous T-Cell lymphoma (CTCL). Psoralens are also present in numerous plants, foods, cosmetics, and perfumes.
    B) PHARMACOLOGY: Psoralens are photoactive furocoumarins. These substances bind to DNA when exposed to ultraviolet light to form photoproducts with pyrimidine bases. This action inhibits DNA synthesis in such conditions as psoriasis, and causes a decrease in cell proliferation.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) The toxic effects of psoralens are almost never evidenced without ultraviolet light. These are photosensitizing materials which exert their primary effect on the skin. METHOXSALEN ALONE: Nausea (10%), nervousness, insomnia, and depression. METHOXSALEN WITH UVA: Pruritus (10%), mild, transient erythema. OTHER EFFECTS: Edema, dizziness, headache, malaise, hypopigmentation, vesiculation and bullae formation, rash, urticaria, folliculitis, abdominal pain, leg cramps, hypotension, conjunctivitis, keratitis, dry eyes, and visual defects.
    E) WITH POISONING/EXPOSURE
    1) There have been some infrequent reports of adverse events reported with the ingestion of herbal products. Fructus psoraleae, the seeds of the Psoralea corylifolia (Babchi), have been used in proprietary herbal products in China. Several cases of transient acute hepatitis in adults have been reported with the use of these products. METHOXSALEN: Overdose effects are anticipated to be an extension of adverse effects following therapeutic doses.
    0.2.20) REPRODUCTIVE
    A) Studies conducted in rats revealed that birthweights were reduced in female rats after males and females were treated with psoralens. Female rats had a reduced number of implantation sites, pups, and corpora lutea when given bergapten and xanthotoxin.
    0.2.21) CARCINOGENICITY
    A) Studies have shown the patients with a history of methotrexate, ionizing radiation, or skin types I or II have an increased chance of developing cutaneous carcinomas when psoralen-UV light therapy is used.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status following significant overdose.
    C) Monitor serum electrolytes in patients with significant nausea and vomiting.
    D) Monitor liver enzymes and CBC following significant overdose.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Avoidance of ultraviolet light is the only specific therapy. Severely exposed patients should be kept in a darkened room for 8 to 48 hours (at least 24 hours for methoxsalen) depending on which psoralen is involved. Manage mild hypotension with IV fluids.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe nausea and vomiting. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. Burn therapy may include topical treatment, pain management, and fluid resuscitation as indicated.
    C) DECONTAMINATION
    1) PREHOSPITAL: Large doses of psoralens may induce spontaneous vomiting. Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    2) HOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    D) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with severe respiratory distress.
    E) ANTIDOTE
    1) None.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home. Avoidance of ultraviolet light is the only specific therapy.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    G) PITFALLS
    1) When managing a suspected overdose, the possibility of multidrug involvement should be considered.
    H) PHARMACOKINETICS
    1) METHOXSALEN: Absorption: Generally well absorbed orally (95%), except for trioxsalen which is poorly absorbed. Tmax: 1 to 4 hours after ingestion of a hard capsule formulation. Protein binding: 90% bound to serum proteins. Vd: Range, 1 to 9 L/kg. Metabolism: Methoxsalen is extensively metabolized in the liver. Excretion: Between 90% to 95% of a dose of methoxsalen is excreted in the urine as metabolites within 24 hours of administration. Elimination half-life: 1/2 to 2 hours.
    I) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause phototoxicity, hypotension, or hepatotoxicity.
    0.4.4) EYE EXPOSURE
    A) UV absorbing wrap should be used around sunglasses for 24 hours after methoxsalen ingestions. This decreases the potential for cataract formation.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) The body should be shielded from sunlight for at least 48 hours after exposure. Topically administered methoxsalen may cause severe local symptoms, if the patient is not properly protected. Topical therapy may be required to treat burn symptoms.
    2) Symptoms of urticaria may require topical steroid therapy.

Range Of Toxicity

    A) TOXICITY: Toxic doses have not been established. Nausea, vomiting, and dizziness developed in an adult after an ingestion of 850 mg of methoxsalen. METHOXSALEN: 10 to 70 mg (based on weight; approximately 0.6 mg/kg) orally 1.5 to 2 hours before UVA exposure not more often than once every 48 hours.

Clinical Effects

Summary Of Exposure

    A) USES: Psoralens are photosensitizing agents, used in combination with ultraviolet light (PUVA therapy) in the treatment of various skin conditions to enhance repigmentation. Methoxsalen is used to treat psoriasis and vitiligo. It is also used as a palliative treatment of the skin manifestations of cutaneous T-Cell lymphoma (CTCL). Psoralens are also present in numerous plants, foods, cosmetics, and perfumes.
    B) PHARMACOLOGY: Psoralens are photoactive furocoumarins. These substances bind to DNA when exposed to ultraviolet light to form photoproducts with pyrimidine bases. This action inhibits DNA synthesis in such conditions as psoriasis, and causes a decrease in cell proliferation.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) The toxic effects of psoralens are almost never evidenced without ultraviolet light. These are photosensitizing materials which exert their primary effect on the skin. METHOXSALEN ALONE: Nausea (10%), nervousness, insomnia, and depression. METHOXSALEN WITH UVA: Pruritus (10%), mild, transient erythema. OTHER EFFECTS: Edema, dizziness, headache, malaise, hypopigmentation, vesiculation and bullae formation, rash, urticaria, folliculitis, abdominal pain, leg cramps, hypotension, conjunctivitis, keratitis, dry eyes, and visual defects.
    E) WITH POISONING/EXPOSURE
    1) There have been some infrequent reports of adverse events reported with the ingestion of herbal products. Fructus psoraleae, the seeds of the Psoralea corylifolia (Babchi), have been used in proprietary herbal products in China. Several cases of transient acute hepatitis in adults have been reported with the use of these products. METHOXSALEN: Overdose effects are anticipated to be an extension of adverse effects following therapeutic doses.

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) PHOTOPHOBIA has been reported during psoralen therapy (Fenton & Wilkinson, 1983).
    2) CONJUNCTIVITIS has been reported during psoralen therapy (Fenton & Wilkinson, 1983).
    3) KERATITIS and dry eyes have been reported during psoralen therapy (Fenton & Wilkinson, 1983).
    4) VISUAL DEFECTS: These effects appeared reversible when psoralen was reduced (Wilkinson & English, 1983).
    5) CATARACTS may form due to binding with proteins and DNA in the lens. Animals studies indicate that methoxsalen may cause more pigmentary retinopathy than 5-MOP (Ashkenazy et al, 1984).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension has been reported with the use of methoxsalen and ultraviolet A (UVA) therapy (Prod Info methoxsalen oral capsules, 2015).
    B) EDEMA
    1) WITH THERAPEUTIC USE
    a) Edema has been reported with the use of methoxsalen and ultraviolet A (UVA) therapy (Prod Info methoxsalen oral capsules, 2015).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) BRONCHOSPASM
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 34-year-old with history of pollen sensitivity rhinitis and a single occurrence of asthma developed bronchial asthma on 2 occasions 4 hours after ingesting methoxsalen 30 mg (Anderson et al, 1984).
    b) A few cases of bronchoconstriction have been reported after administration of 8-methoxypsoralen (Ramsay & Marks, 1988; Wennerstein, 1987).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) DIZZINESS
    1) WITH THERAPEUTIC USE
    a) Dizziness has been reported with therapeutic use (Prod Info methoxsalen oral capsules, 2015; Wilkinson & English, 1983; Agren-Jonsson & Tegner, 1985).
    B) DEPRESSIVE DISORDER
    1) WITH THERAPEUTIC USE
    a) Depression has been reported with therapeutic use (Prod Info methoxsalen oral capsules, 2015; Wilkinson & English, 1983).
    C) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Headache has been reported with therapeutic use (Prod Info methoxsalen oral capsules, 2015; Wilkinson & English, 1983; Agren-Jonsson & Tegner, 1985).
    D) INSOMNIA
    1) WITH THERAPEUTIC USE
    a) Insomnia has been reported with use (Prod Info methoxsalen oral capsules, 2015; Wilkinson & English, 1983).
    E) FEELING NERVOUS
    1) WITH THERAPEUTIC USE
    a) Nervousness has been reported with the use of methoxsalen monotherapy (Prod Info methoxsalen oral capsules, 2015).
    F) MALAISE
    1) WITH THERAPEUTIC USE
    a) Malaise has been reported with the use of methoxsalen monotherapy (Prod Info methoxsalen oral capsules, 2015)
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SEIZURES
    a) Seizures have been reported in some animal studies (Ljunggren & Mattiasson, 1986).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) WITH THERAPEUTIC USE
    a) Nausea (10%) and abdominal pain have been reported while using psoralen therapy (Prod Info methoxsalen oral capsules, 2015; Wilkinson & English, 1983).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) ACUTE HEPATITIS
    1) WITH POISONING/EXPOSURE
    a) Fructus psoraleae, the seeds of the Psoralea corylifolia (Babchi), have been used in proprietary herbal products in China. Several cases of transient acute hepatitis in adults have been reported with the use of these products (Cheung et al, 2009). Hepatotoxicity also developed in a patient after the use of Psoralea corylifolia to treat vitiligo (Quayson et al, 2015).
    b) Three cases of acute hepatitis were reported in adults given herbal medicines containing Fructus Psoraleae, the dried seed(s) of Psoralea corylifolia. Two patients were taking two proprietary medicines (oral and parenteral formulations) for the treatment of vitiligo that were found to contain psoralen, isopsoralen and bakuchiol. The last patient was a 20-year-old woman who was given a herbal powder for the treatment of flu-like symptoms. In each case, liver enzymes gradually improved after stopping the herbal products (Cheung et al, 2009).
    B) TOXIC HEPATITIS
    1) WITH THERAPEUTIC USE
    a) Toxic hepatitis has been seen after psoralen-UV light therapy (Bjellerno et al, 1979; Pariser & Wyles, 1980).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) KIDNEY DISEASE
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 38-year-old woman developed nephrotic syndrome after ten PUVA treatments (Lam Thuon Mine et al, 1983).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) LEUKEMIA
    1) WITH THERAPEUTIC USE
    a) Effects seen while on psoralen and ultraviolet light therapy include myeloid leukemia and a mild transient inhibition of platelet aggregability and thrombocytopenia (Wilkinson & English, 1983).
    B) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) Effects seen while on psoralen and ultraviolet light therapy include myeloid leukemia and a mild transient inhibition of platelet aggregability and thrombocytopenia (Wilkinson & English, 1983).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DISCOLORATION OF SKIN
    1) WITH THERAPEUTIC USE
    a) Erythema and bizarre pigmentation have been seen (Freund, 1916). At therapeutic doses, methoxsalen will cause more dermal reactions than 5-MOP. Psoralen-ultraviolet erythema has a different onset of action from regular sunburn. Onset is generally 12 to 24 hours, with a maximum effect at 48 to 72 hours. (Wilkinson & English, 1983).
    b) Hypopigmentation has been reported with the use of methoxsalen and ultraviolet A (UVA) therapy (Prod Info methoxsalen oral capsules, 2015).
    B) PHOTOTOXICITY
    1) WITH THERAPEUTIC USE
    a) Phototoxic effects have been reported with psoralen therapy (oral and topical) and exposure to UVA (PUVA therapy) light with both acute and chronic exposure. Topical exposure to psoralens may result in a higher risk in developing phototoxicity than oral therapy (Morison, 1997).
    b) Second-degree burns from psoralen exposure differ in several ways from typical second degree burns: blisters occur superficially within the epidermis, the reaction occurs as a result of excitation between psoralen molecules and cutaneous DNA, the onset and peak reaction may be separated by several hours, and the total duration of the injury is longer (Morison, 1997).
    c) SYMPTOMS: Widespread erythema, pruritus without visible changes in the skin, friction blisters, photo-onycholysis, and dermatitis. Skin injury can progress to epidermal necrosis. Phototoxic effects can easily be misdiagnosed as an exacerbation of psoriasis (Morison, 1997).
    d) CASE SERIES: Fourteen women developed burns after using oral and/or topical psoralens and exposure to UV rays from tanning booths for the purposes of esthetic tanning. The burns ranged from superficial to deep-second degree burns and covered more than 76% of the body surface area on average. Treatment included fluid resuscitation in all cases, pain management, and topical therapy. Hospitalization averaged 11 days. None required skin grafting, although some patients developed scars and abnormal pigmentation (Braye et al, 1997).
    e) CASE REPORT: Severe burn lesions were reported in one adult following exposure to topical methoxsalen which resulted in epidermal necrosis and a permanent alteration in repigmentation (Turegun et al, 1999).
    f) CASE REPORT: A 33-year-old woman developed superficial partial thickness burns over approximately 70% of her body after taking an aromatherapy bath using 6 drops of oil of Bergamot (5 hydroxypsoralen) and 6 drops of Geranium oil in the bath water. The patient then used a sun bed for approximately 20-30 minutes 3 hours after the bath and noted no ill effects until 48 hours later when erythema and blistering developed (Cocks & Wilson, 1998).
    C) URTICARIA
    1) WITH THERAPEUTIC USE
    a) Urticaria has been reported with the use of methoxsalen and ultraviolet A (UVA) therapy (Prod Info methoxsalen oral capsules, 2015).
    b) CASE REPORT: A 46-year-old woman with a history of eczema was treated with oral methoxsalen and UV therapy and developed wheals, edema, and erythema. The patient was rechallenged with 40 mg of methoxsalen orally without UVA irradiation. Symptoms of itching and wheals developed on the face within 30 minutes progressing to generalized symptoms 3 hours postingestion. Symptoms resolved with oral and topical corticosteroid therapy. The patient reported similar, but milder symptoms after the ingestion of lime juice (a furocoumarin-containing food) (Bech-Thomsen & Wulf, 1994).
    D) ITCHING OF SKIN
    1) WITH THERAPEUTIC USE
    a) Pruritus occurs in about 10% of people on PUVA therapy (Prod Info methoxsalen oral capsules, 2015; Wilkinson & English, 1983).
    E) PHOTOSENSITIVITY
    1) WITH THERAPEUTIC USE
    a) The photodermatitis seen with these compounds is does NOT usually involve erythema and bullae which form 18 to 24 hours after sunlight exposure. It does not appear to be due to any antibody-antigen reaction, or a cell-mediated hypersensitivity (Wilkinson & English, 1983)
    1) Reactions usually involve erythema and bullae which form 18 to 24 hours after sunlight exposure (Wilkinson & English, 1983).
    2) The faded lesions may show hyperpigmentation for months. Negative effects of psoralen use includes severe skin pain, pruritus, disseminated granuloma annulare, and acneform eruptions (Wilkinson & English, 1983).
    F) DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Patients treated with PUVA have developed contact allergy that was confirmed by patch testing (Saihan, 1979).
    2) WITH POISONING/EXPOSURE
    a) Occupational dermatitis has been reported in parsley harvesters who were also exposed to the sun (Smith, 1985).
    G) KERATOSIS
    1) WITH THERAPEUTIC USE
    a) Manifestations included papules, actinic keratosis-like macules, non-scaling dome-shaped papules, and lichenoid porokeratotic like papules (Prod Info methoxsalen oral capsules, 2015).
    H) BULLOUS DERMATOSIS
    1) WITH THERAPEUTIC USE
    a) Vesiculation and bullae formation have been reported with the use of methoxsalen and ultraviolet A therapy (Prod Info methoxsalen oral capsules, 2015).
    I) ERYTHEMA
    1) WITH THERAPEUTIC USE
    a) Mild, transient erythema at 24 to 48 hours after therapy is expected (Prod Info methoxsalen oral capsules, 2015).
    b) Erythema grade 2 (moderate) or greater that appears within the first 24 hours after ultraviolet A treatment may indicate a severe burn that may progress over the next 24 hours (Prod Info methoxsalen oral capsules, 2015).
    J) NAIL FINDING
    1) WITH THERAPEUTIC USE
    a) PHOTO-ONYCHOLYSIS has been noted on more than one occasion during methoxsalen therapy (20 mg/day) in the summer months (Zala et al, 1977).
    b) NAIL PIGMENTATION: 4 of 14 Indian patients with vitiligo developed nail pigmentation after treatment with methoxsalen for 2 months (Naik & Singh, 1979).
    K) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Rash has been reported with the use of methoxsalen and ultraviolet A (UVA) therapy (Prod Info methoxsalen oral capsules, 2015).
    L) FOLLICULITIS
    1) WITH THERAPEUTIC USE
    a) Folliculitis has been reported with the use of methoxsalen and ultraviolet A (UVA) therapy (Prod Info methoxsalen oral capsules, 2015).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) CRAMP IN LOWER LIMB
    1) WITH THERAPEUTIC USE
    a) Leg cramps have been reported with the use of methoxsalen and ultraviolet A (UVA) therapy (Prod Info methoxsalen oral capsules, 2015).
    B) GOUT
    1) WITH THERAPEUTIC USE
    a) Although a series of cases have been done showing no increase in serum uric acid levels, acute gout has been reported (Burnett, 1982).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) DISORDER OF IMMUNE FUNCTION
    1) WITH THERAPEUTIC USE
    a) Various immunologic defects have been reported including decreases in lymphocyte transformation and T-cell populations (Haftek et al, 1979), Langerhans cells disappearing (Friedmann, 1981), and induction of giant Langerhans cells (Juhlin & Shelley, 1979).
    B) BRONCHOSPASM
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 34-year-old with history for pollen sensitivity rhinitis and a single occurrence of asthma developed bronchial asthma on 2 occasions 4 hours after ingesting methoxsalen 30 mg (Anderson et al, 1984).

Reproductive

    3.20.1) SUMMARY
    A) Studies conducted in rats revealed that birthweights were reduced in female rats after males and females were treated with psoralens. Female rats had a reduced number of implantation sites, pups, and corpora lutea when given bergapten and xanthotoxin.
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) Studies conducted in rats revealed that birthweights were reduced in female rats after males and females were treated with psoralens (Diawara et al, 1999). It was found that female rats had a reduced number of implantation sites, pups, and corpora lutea when given bergapten and xanthotoxin (synthetic forms of 5-methoxypsoralen and 8-methoxypsoralen, respectively).
    2) Decreased uterine weight was observed as well as a reduced circulation in estrogen levels in a dose-dependent manner. The authors suggested that enhanced oxidative metabolism and conjugation of estrogens in psoralen-treated animals may provide some evidence for the effects observed.

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) Studies have shown the patients with a history of methotrexate, ionizing radiation, or skin types I or II have an increased chance of developing cutaneous carcinomas when psoralen-UV light therapy is used.
    3.21.3) HUMAN STUDIES
    A) SKIN CARCINOMA
    1) SUMMARY
    a) Multiple basal cell carcinoma was reported in a patient who had received arsenic in the past, and a current course of psoralen therapy (Moller & Howitz, 1976). However, the idea of arsenic-PUVA promoting keratoses more than arsenic alone seems to have been disproven by Angele et al (1983).
    b) Studies have shown that patients with a history of methotrexate, ionizing radiation, or skin types I or II have an increased chance of developing cutaneous carcinomas when psoralen-UV light therapy is used (Stern et al, 1979).
    c) Although PUVA has proven to be a complete carcinogen in mice it has not been determined how it promotes cancers in humans (Bethea et al, 1999).
    2) CASE SERIES - A prospective study of 1380 patients over 5 years demonstrated a 9 times greater risk of squamous cell carcinoma in patients using PUVA (Melskin et al, 1977).
    3) CASE SERIES - A prospective cohort study of 1380 patients with psoriasis were followed for the development of cancers related to receiving high-dose oral psoralen and ultraviolet-A light (PUVA) treatment (Stern et al, 1998). The study indicated that persistent, dose-related exposure increase in the risk of squamous cell cancer related to PUVA therapy; the risk of basal cell cancer was less affected by PUVA therapy.
    a) In this study, squamous cell carcinoma resulted in increased morbidity and mortality. 9 (3.8%) of 237 patients with squamous cell carcinoma developed metastases and 22 (2.5%) of 876 male patients had invasive or in situ squamous cell carcinoma of the penis or scrotum. No metastases were reported for the diagnosis of basal cell cancer in this study. Malignant melanoma has been reported following PUVA therapy (Stern et al, 1998; Lindelof, 1999).
    b) European epidemiological surveys showed NO direct correlation between PUVA and an increase in skin cancer risk.
    c) Gibbs et al (1986) proposed that this difference in cancer risk between the US and Europe may be explained by differences in therapeutic strategy. The strategy used in the US, combination of low-dose and extended treatment times, may increase tumor risk.
    d) The European approach, individualized dose given more frequently per week over shorter periods of time, may reduce tumor risk.
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) Animal tests have shown an increased incidence of ear tumors, squamous cell carcinomas, and fibrosarcomas (O'Neal & Griffin, 1957).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status following significant overdose.
    C) Monitor serum electrolytes in patients with significant nausea and vomiting.
    D) Monitor liver enzymes and CBC following significant overdose.

Methods

    A) CHROMATOGRAPHY
    1) Psoralens may be measured using high-pressure liquid chromatography (HPLC) (Ljunggren & Mattiasson, 1986), reverse-phase HPLC is the method of choice for determining methoxsalen in body fluids (de Wolff & Thomas, 1986).
    2) Ketchum et al (1990) described a rapid and simple method for assaying 8-MOP in plasma by high performance liquid chromatography, which uses solid-phase extraction column and one reagent to simplify the sample preparation (Ketchum et al, 1990).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home. Avoidance of ultraviolet light is the only specific therapy.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status following significant overdose.
    C) Monitor serum electrolytes in patients with significant nausea and vomiting.
    D) Monitor liver enzymes and CBC following significant overdose.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Gastrointestinal decontamination is generally not necessary unless extremely large amounts have been ingested. Large doses of psoralens may induce spontaneous vomiting.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Gastrointestinal decontamination is not necessary unless extremely large amounts have been ingested. Large doses of psoralens may induce spontaneous vomiting. Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is symptomatic and supportive. Manage mild hypotension with IV fluids. Avoidance of ultraviolet light is the only specific therapy. Severely exposed patients should be kept in a darkened room for 8 to 48 hours (at least 24 hours for methoxsalen) depending on which psoralen is involved.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe nausea and vomiting. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. Burn therapy may include topical treatment, pain management, and fluid resuscitation as indicated.
    3) Polaroid-like sunglasses should be recommended for patients sensitized to UV light (Moseley et al, 1988). These glasses should be worn for several weeks when in sunlight.
    B) MONITORING OF PATIENT
    1) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    2) Monitor vital signs and mental status following significant overdose.
    3) Monitor serum electrolytes in patients with significant nausea and vomiting.
    4) Monitor liver enzymes and CBC following significant overdose.
    C) BURN
    1) Superficial to deep second degree burns have been reported in females following oral and topical psoralens and exposure to UV light (Braye et al, 1997). Treatment is symptomatic and supportive. Fluid replacement, pain management, and topical therapy may be required.
    D) URTICARIA
    1) Urticaria symptoms have been reported following oral psoralen and UV therapy (Bech-Thomsen & Wulf, 1994). Symptoms may require topical or oral steroid therapy.
    E) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

Eye Exposure

    6.8.2) TREATMENT
    A) SUPPORT
    1) UV-absorbing wrap should be used around sunglasses for 24 hours after methoxsalen ingestion. This decreases the potential for cataract formation.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.2) TREATMENT
    A) SUPPORT
    1) The body should be shielded from sunlight for at least 48 hours after exposure. Topically administered methoxsalen may cause severe local symptoms. Burn therapy may include topical treatment, pain management, and fluid resuscitation as indicated.
    B) URTICARIA
    1) Treatment should be based on the severity of the symptoms. Topical and/or oral corticosteroids may assist in resolution of urticaria.
    2) An urticarial reaction including wheals and itching was successfully treated with oral and topical steroids following oral psoralen and UV therapy (Bech-Thomsen & Wulf, 1994).
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Abstracts

Case Reports

    A) ADULT
    1) A 25-year-old women took about 85 Puvamet tablets at approximately in a suicide attempt. Eighty-five Puvamet corresponds to about 850 mg methoxsalen. In a short period of time she began to feel nauseated. She was brought to a health care facility by relatives an hour later. After admission she was kept in a dark room on a cardiac monitor continuously for 24 hours. The patient experienced nausea and vomiting until the following day. She complained of dizziness and was examined by a neurologist on the afternoon of day one. No objective neurologic findings were noted and the dizziness did not affect the patients ability to stand. All laboratory tests were normal and she was feeling well at 36 hours post-admission. Eight-MOP levels in serum was determined by high-pressure liquid chromatography at 9, 10, and 32 hours postingestion. Serum levels were reported at 606, 584, and 21 mg/mL, respectively. All other laboratory parameters tested were within normal limits the day of ingestion, one day postingestion and 2 weeks postingestion (Ljunggren & Mattiasson, 1986).

Range Of Toxicity

Summary

    A) TOXICITY: Toxic doses have not been established. Nausea, vomiting, and dizziness developed in an adult after an ingestion of 850 mg of methoxsalen. METHOXSALEN: 10 to 70 mg (based on weight; approximately 0.6 mg/kg) orally 1.5 to 2 hours before UVA exposure not more often than once every 48 hours.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) 5-Methoxypsoralen (bergapton) (5-MOP) has been used topically and orally in the photochemical treatment of psoriasis (Honigsmann et al, 1979).
    2) METHOXSALEN-
    a) PSORIASIS - Doses are based upon the patient's weight (approximately 0.6 milligram/kilogram orally), and the drug is taken 1.5 to 2 hours prior to UVA exposure with food or milk, according to the following table (kg=kilogram, lb=pound, mg=milligram) (Prod Info Oxsoralen-Ultra(R), methoxsalen, 1996).
    b) VITILIGO - For repigmentation of larger lesions (greater than 6 centimeters squared) of idiopathic vitiligo, oral therapy is indicated. The recommended oral dose is 2 capsules of METHOXSALEN/day (10 milligrams each) taken with milk or food, 2 to 4 hours prior to UVA light exposure. The exposure time should be limited to 5 minutes initially, gradually increasing to 30 minutes if required (Prod Info 8-MOP(R), methoxsalen, 1996) AMA, 1985).
    7.2.2) PEDIATRIC
    A) SPECIFIC SUBSTANCE
    1) The American Academy of Pediatrics has not approved the use of PUVA therapy in children, primarily due to the potential of carcinogenicity (Segal et al, 1978).

Minimum Lethal Exposure

    A) TOXICITY: Toxic doses have not been established. Nausea, vomiting, and dizziness developed in an adult after an ingestion of 850 mg of methoxsalen. METHOXSALEN: 10 to 70 mg (based on weight; approximately 0.6 mg/kg) orally 1.5 to 2 hours before UVA exposure not more often than once every 48 hours.

Maximum Tolerated Exposure

    A) FRUCTUS PSORALEAE
    1) CASE REPORT: Three cases of acute hepatitis were reported in adults given herbal medicines containing Fructus Psoraleae, the dried seed(s) of Psoralea corylifolia. Two patients were taking two proprietary medicines (an oral and parenteral formulation) for the treatment of vitiligo that were found to contain psoralen, isopsoralen and bakuchiol. The last patient was a 20-year-old woman who was given a herbal powder for the treatment of flu-like symptoms. In each case, liver enzymes gradually improved after stopping the herbal products (Cheung et al, 2009).
    B) METHOXSALEN
    1) CASE REPORT: A 25-year-old patient ingested the equivalent of 850 mg methoxsalen and developed nausea, vomiting and dizziness was reported. The patient was monitored closely and kept in a dark room for 24 hours. The patient was feeling well at 36 hours postingestion (Ljunggren & Mattiasson, 1986).
    2) ANIMAL STUDIES: Methoxsalen by the oral route in mice and rats: Varied between 400 and 800 mg/kg. Clinical effects consisted of hypoactivity, ataxia, prostration, muscle twitches, and seizures (Ljunggren & Mattiasson, 1986).

Physicochemical

Physical Characteristics

    A) BERGAMOT OIL: greenish or brown-yellow oil with fragrant odor and bitter aromatic taste (JEF Reynolds , 2000)
    B) METHOXSALEN: white to cream-colored, fluffy, needle-like crystals that are odorless (JEF Reynolds , 2000)
    C) TRIOXSALEN: white to off-white or grey crystalline solid that has no odor (JEF Reynolds , 2000)

Molecular Weight

    A) METHOXSALEN: 216.2 (JEF Reynolds , 2000)
    B) TRIOXSALEN: 228.2 (JEF Reynolds , 2000)

References

General Bibliography

    1) Agren-Jonsson S & Tegner E: PUVA therapy for Palmoplantar Pustulosis. Acta Derm Venereol (Stockh) 1985; 65:531-535.
    2) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    3) Anderson CD, Frodin T, & Skogh M: Unusual adverse effects of 8-methoxypsoralen: bronchial reaction during photochemotherapy (PUVA) (letter). J Am Acad Dermatol 1984; 10:298.
    4) Ashkenazy D, Friedman J, & Kashman Y: Photosensitization in duckling's induced by Pituranthos triradiatas. Vet Hum Toxicol 1984; 26:118-120.
    5) Ashwood-Smith MJ, Ceska O, & Chaudhary SK: Mechanisms of photosensitivity reactions to diseased celery. Br Med J 1985; 290:1249.
    6) Bech-Thomsen N & Wulf HC: 8-Methoxypsoralen urticaria (letter). J Am Acad Dermatol 1994; 31:1063-1064.
    7) Bethea D, Fullmer B, & Syed S: Psoralen photobiology and photochemotherapy: 50 years of science and medicine. J Dermatol Sci 1999; 19:78-88.
    8) Bjellerno M, Bruze M, & Hansson: Liver injury following administration of 8-Methoxypsoralen during PUVA therapy. Acta Dermatol 1979; 59:371-372.
    9) Braye F, Latarjet J, & Foyatier JL: Extensive burns caused by the abusive use of photosensitizing agents. J Burn Care Rehabil 1997; 18:321-325.
    10) Cheung WI, Tse ML, Ngan T, et al: Liver injury associated with the use of Fructus Psoraleae (Bol-gol-zhee or Bu-gu-zhi) and its related proprietary medicine. Clin Toxicol (Phila) 2009; 47(7):683-685.
    11) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    12) Cocks H & Wilson D: Dangers of the intake of psoralens and subsequent UV exposure producing significant burns. Burns 1998; 24:82.
    13) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    14) Diawara MM, Chavez KJ, & Hoyer PB: A novel group of ovarian toxicants: the psoralens. J Biochem Molecul Toxicol 1999; 13:195-203.
    15) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    16) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    17) Fenton DA & Wilkinson JD: Dose-related visual-field defects in patients receiving PUVA therapy (letter). Lancet 1983; 1:1106.
    18) Freund E: Uber bisher noch nicht beschriebene kunstliche. Hant Farb Dermatol Wochenschr 1916; 63:931-933.
    19) Friedmann PS: Disappearance of epidermal langerhans cells during PUVA therapy. Br J Dermatol 1981; 105:219-221.
    20) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    21) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    22) Grant WM: Toxicology of the Eye, 3rd ed, Charles C. Thomas, Springfield, IL, 1986.
    23) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    24) Haftek M, Glinski W, & Jablonski S: T-lymphocyte E resette function during photochemotherapy (PUVA). J Invest Dermatol 1979; 72:214-218.
    25) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    26) Honigsmann H, Jaschke E, & Gschnait F: 5-Methoxypsoralen (Bergapten) in photochemotherapy of psoriasis. Br J Dermatol 1979; 101:369-378.
    27) JEF Reynolds : Martindale: The Extra Pharmacopoeia (electronic version - Volume 104). The Pharmaceutical Press. London, UK (Internet Version). Edition expires 2000; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    28) Juhlin L & Shelley WB: Giant Langerhans cells induced by psoralen and ultraviolet radiation. Arch Dermatol Res 1979; 266:311-314.
    29) Ketchum CH, Robinson A, & Huang ST: Analysis of 8-Methoxypsoralen by high-performance liquid chromatography. Clin Chem 1990; 36:1956-1957.
    30) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    31) Lindelof B: Risk of melanoma with psoralen/ultraviolet A therapy for psoriasis. Do the known risks now outweigh the benefits?. Drug Safety 1999; 20:289-297.
    32) Ljunggren B & Mattiasson I: Acute methoxsalen intoxication. J Am Acad Dermatol 1986; 15:533.
    33) Melskin JW, Tanenbaum L, & Parrish F: Oral methoxsalen photochemotherapy for the treatment of psoriasis: a cooperative clinical trial. J Invest Derm 1977; 68:328.
    34) Moller R & Howitz J: Methoxsalen and multiple basal cell carcinomas (letter). Arch Dermatol 1976; 112:1613-1614.
    35) Morison WL: Subacute phototoxicity caused by treatment with oral psoralen plus UV-A (letter). Arch Dermatol 1997; 133:1609.
    36) Moseley H, Cox NH, & Mackie RM: The suitability of sunglasses used by patients following ingestion of psoralen. Br J Dermatol 1988; 118:247-253.
    37) Naik RPC & Singh G: Nail pigmentation due to oral 8-methoxypsoralen. Br J Dermatol 1979; 100:229-230.
    38) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    39) O'Neal MA & Griffin AC: The effect of oxypsoralen upon ultraviolet carcinogenesis in albino mice. Cancer Res 1957; 17:911-916.
    40) Pariser DM & Wyles R: Toxic hepatitis from oral methoxsalen photochemotherapy (PUVA). J Am Acad Dermatol 1980; 3:248-250.
    41) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    42) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    43) Product Information: 8-MOP(R) oral capsules, methoxsalen oral capsules. ICN Pharmaceuticals,Inc, Costa Mesa, CA, 2003.
    44) Product Information: 8-MOP(R), methoxsalen. ICN Pharmaceuticals Inc, Costa Mesa, CA, 1996.
    45) Product Information: Oxsoralen-Ultra(R), methoxsalen. ICN Pharmaceuticals, Costa Mesa, CA, 1996.
    46) Product Information: UVADEX(R) intravenous injection solution, methoxsalen intravenous injection solution. Therakos, Inc. (per FDA), Raritan, NJ, 2013.
    47) Product Information: UVADEX(R) photopheresis solution, methoxsalen photopheresis solution. Ben Venue Laboratories, Bedford, OH, 1999.
    48) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    49) Product Information: methoxsalen oral capsules, methoxsalen oral capsules. Actavis Pharma, Inc. (per DailyMed), Parsippany, NJ, 2015.
    50) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    51) Quayson E, Berman AJ, Regina AC, et al: Hepatotoxicity Associated with the Use of Psoralea corylifolia Used to Treat Vitiligo. Clin Toxicol (Phila) 2015; 53(7):741.
    52) Ramsay B & Marks JM: Bronchoconstriction due to 8-methoxypsoralen. Br J Dermatol 1988; 119:83-86.
    53) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    54) Saihan EM: Contact allergy to methoxsalen. Br Med J 1979; 2:20.
    55) Smith DM: Occupational photodermatitis from parsley. Practitioner 1985; 229:673-675.
    56) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    57) Stern RS, Liebman EJ, & Vakeva L: Oral psoralen and ultraviolet-A light (PUVA) treatment of psoriasis and persistent risk of nonmelanoma skin cancer. J Natl Cancer Inst 1998; 90:1278-1284.
    58) Stern RS, Thiobodeau LA, & Kleinerman RA: Risk of cutaneous carcinoma in patients treated with oral methoxsalen photochemotherapy for psoriasis. N Engl J Med 1979; 300:809-813.
    59) Tamaro M, Gastaldi S, & Carlassare F: Genotoxic activity of some water-soluble derivatives of 5-mthoxypsoralen and 8-methoxypsoralen. Carcinogenesis 1986; 7:605-609.
    60) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    61) Turegun M, Ozturk S, & Selmanpakoglu N: An unusual cause of burn injury: unsupervised use of drugs that contain psoralens. J Burn Care Rehabil 1999; 20:50-52.
    62) Vale PT: Prevention of phytophotodermatitis from celery. Contact Derm 1993; 29:108.
    63) Wennerstein G: Exacerbation of bronchial asthma during photochemotherapy with 8-methoxysoralen and UVA (PUVA). Phytodermatology 1987; 4:212-213.
    64) Wilkinson JD & English J: Psoralens. Semin Derm 1983; 2:85-100.
    65) de Wolff FA & Thomas TV: Clinical pharmacokinetics of methoxsalen and other psoralens. Clin Pharmacokinet 1986; 11:62-75.