      Document 0159
 DOCN  DRG0159
 UNIQUE IDENTIFIER        DRG-0088
 NAME OF SUBSTANCE        Methoxsalen [USAN 1996]
 REGISTRY NUMBER          298-81-7
 STANDARD CHEMICAL NAME   9-Methoxy-7H-furo(3,2-g)(1)benzopyran-7-one
                          [USAN 1996]
 SYNONYMS                 8-MOP [Merck Index 1989]
 SYNONYMS                 8-MP [Merck Index 1989]
 SYNONYMS                 Meladinine [Merck Index 1989]
 SYNONYMS                 Methoxa-Dome [USAN 1996]
 SYNONYMS                 Oxsoralen Ultra [USAN 1996]
 SYNONYMS                 Psoralon-MOP [Merck Index 1989]
 SYNONYMS                 8-Methoxy-4', 5':6, 7-furocoumarin [Merck
                          Index 1989]
 SYNONYMS                 8-Methoxy(furano-3', 2':6-7-coumarin [Merck
                          Index 1989]
 SYNONYMS                 Xanthotoxin [Merck Index 1989]
 SYNONYMS                 Ammoidin [Merck Index 1989]
 SYNONYMS                 9-Methoxypsoralen [Merck Index 1989]
 SYNONYMS                 Meloxine [USAN 1996]
 SYNONYMS                 Oxsoralen Lotion [USAN 1996]
 SYNONYMS                 Uvadex [USAN 1996]
 SYNONYMS                 8-Methoxypsoralen [USAN 1996]
 PROTOCOL ID NUMBERS      FDA 049A
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Following photoactivation,
                          methoxsalen forms covalent bonds with DNA to
                          produce monofunctional (addition to a single
                          bond of DNA) and bifunctional adducts (cross
                          linking to both strands of DNA). Reactions
                          with other proteins also occur. Since the
                          half-life of the photoactivated methoxsalen
                          is in the microsecond range, tissues not
                          simultaneously exposed to both the drug and
                          ultraviolet A are spared the toxic effects of
                          the active form. Methoxsalen appears to be
                          well, but variably absorbed from the GI tract
                          following oral administration. When
                          administered orally with food, the extent of
                          absorption and peak serum concentration
                          appear to increase. The drug appears to be
                          preferentially taken up by epidermal cells;
                          distributes into the lens of the eye in
                          concentrations proportional to the serum
                          concentrations. The drug is reportedly 75-91
                          % bound to serum proteins, principally
                          albumin. About 95 % of the drug is excreted
                          in urine within 24 hours as metabolites. UVAR
                          system: Oral ingestion of methoxsalen is
                          followed by withdrawal of blood from the
                          patient. This blood is infused into the UVAR
                          system and red cells and plasma are
                          immediately returned to the patient. Before
                          the leukocyte fraction is returned to the
                          patient, it is exposed to UV radiation which
                          activates the methoxsalen. Methoxsalen
                          becomes an alkylating agent that deactivates
                          when no longer exposed to the light. The
                          treated white cells, unable to reproduce, are
                          returned to the patient. [Facts and
                          Comparisons 1995] [AHFS Drug Information
                          1995] [N Eng J Med 1987 Feb;316(6)]
 DISEASES STUDIED/TREATED AIDS-Related Complex [Dermatol Nurs Feb;5(1)]
 CLASSIFICATION CODE      Photochemotherapeutic [Drug Evaluations
                          Annual 1992]
 CLASSIFICATION CODE      Pigmentation [USAN 1996]
 OTHER MAJOR USES         Idiopathic vitiligo, psoriasis, and cutaneous
                          T-cell lymphoma [AHFS Drug Information 1995]
 SUBSTANCE INTERACTIONS   Other photosensitizing drugs (eg,
                          phenothiazines, tar) should be administered
                          with caution. High concentrations of topical
                          methoxsalen and overexposure to UVA radiation
                          can cause toxic reactions. Therefore,
                          methoxsalen must be diluted and UVA exposure
                          controlled. Food increases methoxsalen
                          absorption. [AHFS Drug Information 1995] [PDR
                          1995]
 ADVERSE EFFECTS          Toxic topical reactions: severe erythema and
                          blistering or nausea. Oral reaction: Gastric
                          discomfort occasionally follows oral
                          administration and is minimized by giving the
                          drug with milk or meals. If overdose of drug
                          occurs, patient should remain in a darkened
                          room for eight hours or until cutaneous
                          reactions subside. UVAR system: post
                          reinfusion temperature elevations. [PDR 1995]
                          [New Eng J Med 1987 Feb 5;316(6)]
 CONTRAINDICATIONS        Contraindicated in patients exhibiting
                          idiosyncratic reactions to psoralens or with
                          a history of a sensitivity reaction to the
                          drug; those with diseases associated with
                          photosensitivity; patients with aphakia
                          (absence of lenses) because of the increased
                          risk of retinal damage. Also contraindicated
                          in patients with hepatic diseases or
                          insufficiency, children 12 years of age and
                          younger. FDA pregnancy category C. [PDR 1995]
                          [AHFS Drug Information 1995] [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Methoxsalen is a naturally
                          occurring substance found in the seeds of the
                          Ammi majus (Umbelliferae) plant [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: It belongs to a group of
                          compounds known as psoralens or furocoumarins
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: It is prepared
                          synthetically for commercial use [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Methoxsalen undergoes
                          extracorporeal photoactivation by ultraviolet
                          A light [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 216.19 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C12H8O4 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Practically insoluble in water;
                          slightly soluble in alcohol and soluble in
                          propylene glycol [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Occurs as white to
                          cream-colored fluffy, odorless, needle-like
                          crystals [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C66.67%, H3.73%,
                          O29.60% [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Casules 10 mg; lotion 1%
                          (Oxsoralen; Oxsoralen-Ultra). [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Topical with area
                          subsequently exposed to UVA radiation. [AHFS
                          Drug Information 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral administration is
                          recommended for larger areas of involvement.
                          [AHFS Drug Information 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at room temperature: 15 to 30
                          C (59-86 F), protect from light. [USP DI
                          1995]
 MANUFACTURERS            Therakos
 REFERENCES               Lightfoote M, Beer JZ, Smudzka B, Gregory N.
                          Modulation of immune response and HIV antigen
                          expression in UVB-treated psoriasis patients.
                          Int Conf AIDS. 1994 Aug 7-12;10(2):184
                          (abstract no. PB0750).
 REFERENCES               Lin L, Londe H, Hanson CV, Wieshahn G, Isaacs
                          S, Cimino G, Corash L. Photochemical
                          inactivation of cell-associated human
                          immunodeficiency virus in platelet
                          concentrates. Blood. 1993 Jul 1;82(1):292-7.
 REFERENCES               Cahill C, Keyes B, Crater D, Meyer K, et al.
                          Photopheresis for ARC: a nursing perspective.
                          Dermatol Nurs. 1993 Feb;5(1):39-41.
 REFERENCES               Heald P, Rook A, Perez M, Wintroub B, et al.
                          Treatment of erythrodermic cutaneous T-cell
                          lymphoma with extracorporeal
                          photochemotherapy. J Am Acad Dermatol. 1992
                          Sep;27(3):427-33.
 REFERENCES               Fossel ET, Fletcher JG, McDonagh J, Hui KK.
                          Selective cytotoxicity of low-density
                          lipoprotein to helper T cells of cutaneous
                          T-cell lymphoma after photoperoxidation with
                          8-methoxypsoralen. J Natl Cancer Inst. 1991
                          Sep 18;83(18):1316-21.
 REFERENCES               Zmudzka BZ, Beer JZ, Olvey KM, Strickland AG,
                          Lee W, Jacobs ME. Activation of the HIV
                          promoter by radiation and drugs. Int Conf
                          AIDS. 1991 Jun 16-21;7(1):149 (abstract no.
                          M.A.1229).
 REFERENCES               Abrutyn E. Photopheresis and human
                          immunodeficiency virus (HIV) infection: the
                          Annals views preliminary reports [editorial;
                          comment]. Ann Intern Med. 1990 Aug
                          15;113(4):263-4.
 ENTRY MONTH              9007
 LAST REVISION DATE       960206
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
