      Document 0197
 DOCN  DRG0197
 UNIQUE IDENTIFIER        DRG-0050
 NAME OF SUBSTANCE        Methylprednisolone [USAN 1996]
 REGISTRY NUMBER          83-43-2
 RELATED REGISTRY NUMBER  86401-95-8
 RELATED REGISTRY NUMBER  53-36-1
 RELATED REGISTRY NUMBER  2921-57-5
 RELATED REGISTRY NUMBER  5015-36-1
 RELATED REGISTRY NUMBER  22252-38-6
 RELATED REGISTRY NUMBER  2375-03-3
 RELATED REGISTRY NUMBER  2921-57-5
 RELATED REGISTRY NUMBER  90350-40-6
 STANDARD CHEMICAL NAME   11,17,21-Trihydroxy-6-methyl-pregna-1,4-diene-
                          -3,20-dione [USAN 1996]
 SYNONYMS                 1-Dehydro-6-alpha-methyl-hydroxycortisone
                          [Merck Index 1989]
 SYNONYMS                 Delta-1-6-alpha-methylhydrocortisone [Merck
                          Index 1989]
 SYNONYMS                 6-Alpha-methyl-11-beta, 17-alpha,
                          21-triol-1,4-pregnadiene-3,20-dione [Merck
                          Index 1989]
 SYNONYMS                 Artisone-Wyeth [Merck Index 1989]
 SYNONYMS                 Medrate [Merck Index 1989]
 SYNONYMS                 Medrone [Merck Index 1989]
 SYNONYMS                 Metastab [Merck Index 1989]
 SYNONYMS                 Metrisone [Merck Index 1989]
 SYNONYMS                 Promacortine [Merck Index 1989]
 SYNONYMS                 Suprametil [Merck Index 1989]
 SYNONYMS                 Urbason [Merck Index 1989]
 SYNONYMS                 Medrol (Upjohn) [USAN 1996]
 SYNONYMS                 Depo-Medrol (Acetate) [USAN 1996]
 SYNONYMS                 Methylone (Acetate) [USP DI 1989]
 SYNONYMS                 Solu-Medrol (sodium succinate) [USAN 1996]
 PROTOCOL ID NUMBERS      NIAID ACTG 030
 PROTOCOL ID NUMBERS      NIAID ACTG 170
 SECONDARY SOURCE ID      Code 810 487 207
 SECONDARY SOURCE ID      NSC-19987 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: May cause profound and varied
                          metabolic effects, modifying the body's
                          immune responses to diverse stimuli.
                          Increases salt, calcium, and water retention
                          and decreases potassium excretion.
                          Anti-inflammatory actions include inhibition
                          of accumulation of inflammatory cells
                          (including macrophages and leukocytes) at
                          inflammation sites, and inhibition of
                          phagocytosis, lysosomal enzyme release, and
                          synthesis and/or release of several chemical
                          mediators; immunosuppressant actions may
                          involve prevention/suppression of
                          cell-mediated (delayed hypersensitivity)
                          immune reactions and more specific actions
                          affecting immune response; immunosuppressant
                          actions may also contribute significantly to
                          the anti-inflammatory effect. Oral dose is
                          rapidly and almost completely absorbed from
                          gastrointestinal tract (intramuscular dose of
                          acetate form is slowly but completely
                          absorbed); biotransformation is primarily
                          hepatic; elimination is primarily by renal
                          excretion of inactive metabolites. Oral dose
                          of methylprednisolone has a peak effect of
                          1-2 hours and a duration of action of
                          1.25-1.5 days; intramuscular injection of the
                          acetate form has an onset of action of 6-48
                          hours, a peak effect of 4-8 days, and a
                          duration of action of 1-4 weeks. Intravenous
                          doses (sodium succinate) have a rapid onset
                          of action. [PDR 1995; USP DI 1995]
 DISEASES STUDIED/TREATED Use in high-dose corticosteroid therapy in
                          AIDS patients with Pneumocystis carinii
                          pneumonia (PCP) treated with Pentamidine or
                          Trimethoprim-Sulfamethoxazole [AHFS Drug
                          Information 1995]
 CLASSIFICATION CODE      Anti-inflammatory [PDR 1995]
 CLASSIFICATION CODE      Immunosuppressant [USP DI 1995]
 OTHER MAJOR USES         Adrenocortical function abnormalities;
                          various disorders (allergic; collagen;
                          dermatologic; gastrointestinal;  hematologic;
                          ophthalmic; oral; respiratory; rheumatic);
                          hepatic disease; carcoidosis; nonrheumatic
                          inflammation; neoplastic disease; nephrotic
                          syndrome; neurologic disease [PDR 1995]
 SUBSTANCE INTERACTIONS   May cause neurological complications and lack
                          of antibody response if smallpox vaccine or
                          other immunization vaccines are used while
                          being treated with this drug.  Troleandomycin
                          may decrease metabolism of
                          methylprednisolone; may exhibit interactions
                          with a variety of drugs similar to those
                          reported for other adrenocorticoids having
                          systemic glucocorticoid effects. Concurrent
                          use of cyclosporine can result in inhibition
                          of the metabolism of both drugs. Convulsions
                          have also been reported with concurrent
                          cyclosporine use. Hepatic enzyme inducers may
                          increase the clearance of methylprednisolone
                          and may require an increased dose of the
                          steroid. Aspirin clearance may be increased,
                          decreasing salicylate levels. The activity of
                          anticoagulants has been both decreased and
                          increased by concomitant methylprednisolone.
                          [PDR 1995; USP DI 1995]
 ADVERSE EFFECTS          May cause fluid and electrolyte disturbances
                          and a wide variety of adverse
                          musculoskeletal, gastrointestinal,
                          neurological, endocrine, opthalmic, or
                          metabolic effects.  The 24 mg tablet contains
                          FD&C Yellow No. 5 (tartrazine), which may
                          cause allergic-type reactions, including
                          bronchial asthma, in certain individuals,
                          frequently in patients who also have aspirin
                          hypersensitivity. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated for patients with systemic
                          fungal infections. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Glucocorticoid;
                          adrenocorticoid [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C22H30O5 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 374.48 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C70.56%,
                          H8.08%, O21.36% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 228-237 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Sparingly soluble in alcohol,
                          dioxane, and methanol; slightly soluble in
                          acetone and chloroform; very slightly soluble
                          in ether; practically insoluble in water [PDR
                          1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Practically white,
                          odorless, crystalline powder [PDR 1993]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets containing 2, 4, 8, 16,
                          24, or 32 mg of drug. [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Sterile methylprednisolone
                          acetate suspensions, 20 mg, 40 mg or 80 mg/ml
                          and rectal enema, 40 mg. [PDR 1995; USP DI
                          1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Intravenous and intramuscular
                          sodium succinate injections, 40 mg, 125 mg,
                          500 mg, 1 g, and 2 g vials. [PDR 1995; USP DI
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral, intramuscular,
                          intra-articular, intralesional, soft-tissue
                          injection, or topical application. [USP DI
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Rectal enema application.
                          [USP DI 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous administration.
                          [USP DI 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at controlled room temperature
                          of 15-30 C (59-86 F). Use reconstituted
                          methylprednisolone sodium succinate within 48
                          hours. [USP DI 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Do not use if the solution is cloudy
                          or contains a precipitate. [USP DI 1995]
 MANUFACTURERS            Upjohn
 MANUFACTURERS            Schering-Plough
 REFERENCES               Walmsley S, Levinton C, Brunton J, Muradali
                          D, Rappaport D, Bast M, Spence D, Salit I. A
                          multicenter randomized double-blind
                          placebo-controlled trial of adjunctive
                          corticosteroids in the treatment of
                          Pneumocystis carinii pneumonia complicating
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                          Acquir Immyne Defic Syndr Hum Retrovirol.
                          1995 Apr 1;8(4):348-57.
 REFERENCES               Galli E, Chini L, Moschese V, Paone F,
                          Menichelli A, Fraioli G, Rossi P.
                          Methylprednisolone bolus: a novel therapy for
                          severe atopic dermatitis. Acta Paediatr. 1994
                          Mar;83(3):315-7.
 REFERENCES               Bentsen KD, Nielsen TL, Eaftinck Schattenkerk
                          JK, Jensen BN, Lundgren JD. Serum type III
                          procollagen peptide in patients with
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                          Dis. 1993 Dec;148(6 Pt 1):1558-62.
 REFERENCES               Nielsen TL, Eeftinck Schattenkerk JK, Jensen
                          BN. [Corticosteroid treatment of patients
                          with AIDS and severe Pneumocystis carinii
                          pneumonia. A European multicenter study.
                          Danish-Dutch AIDS Study Group]. Ugeskr
                          Laeger. 1993 Jul 26;155(30):2343-7.
 REFERENCES               Elli A, Rivolta R, Di Palo FQ, Parenti M,
                          Vergallo G, Palazzi P, Zafiropulu S, Abelli
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 REFERENCES               LaRocco A Jr, Amundson DE, Wallace MR, Malone
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 REFERENCES               Staikowsky F, Lafon B, Guidet B, Parrot A,
                          Mayaud C, Offenstadt G. Prognosis of acute
                          respiratory failure (ARF) requiring
                          mechanical ventilation (MV) in AIDS-related
                          Pneumocystis carinii pneumonia (PCP). Int
                          Conf AIDS. 1991 Jun 16-21;7(2):235 (abstract
                          no. W.B.2213).
 REFERENCES               Negri C, Saracco A, Tambussi G, Ruggieri A,
                          Lazzarin A. [Respiratiory complications in 44
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 REFERENCES               Gagnon S, Boota AM, Fischl MA, Baier H,
                          Kirksey OW, La Voie L. Corticosteroids as
                          adjunctive therapy for severe Pneumocystis
                          carinii pneumonia in the acquired
                          immunodeficiency syndrome. A double-blind,
                          placebo-controllled trial. N Engl J Med. 1990
                          Nov 22;323(21):1444-50.
 REFERENCES               Hollak CE, Kersten MJ, van der Lelie J, Lange
                          JM. Thrombocytopenic purpura as first
                          manifestation of human immunodeficiency virus
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 ENTRY MONTH              8906
 LAST REVISION DATE       960311
 

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