      Document 0147
 DOCN  DRG0147
 UNIQUE IDENTIFIER        DRG-0100
 NAME OF SUBSTANCE        Acetylcysteine [USAN 1996]
 REGISTRY NUMBER          616-91-1
 STANDARD CHEMICAL NAME   N-Actetyl-L-cysteine [USAN 1996]
 SYNONYMS                 NAC [Merck Index 1989]
 SYNONYMS                 Mucomyst [USAN 1996]
 SYNONYMS                 Respaire [USAN 1990]
 SYNONYMS                 Airbron [Merck Index 1989]
 SYNONYMS                 Broncholysin [Merck Index 1989]
 SYNONYMS                 Brunac [Merck Indes 1989]
 SYNONYMS                 Fabrol [Merck Index 1989]
 SYNONYMS                 Fluatox [Merck Index 1989]
 SYNONYMS                 Fluimucil [Merck Index 1989]
 SYNONYMS                 Fluimucetin [Merck Index 1989]
 SYNONYMS                 Fluprowit [Merck Index 1989]
 SYNONYMS                 Inspir [Merck Index 1989]
 SYNONYMS                 Mucocedyl [Merck Index 1989]
 SYNONYMS                 Mucolator [Merck Index 1989]
 SYNONYMS                 Mucolyticum [Merck Index 1989]
 SYNONYMS                 Muco Sanigen [Merck Index 1989]
 SYNONYMS                 Mucosolvin [Merck Index 1989]
 SYNONYMS                 Mucosil [PDR 1995]
 SYNONYMS                 Mucret [Merck Index 1989]
 SYNONYMS                 Neo-Fluimucil [Merck Index 1989]
 SYNONYMS                 Parvolex [Merck Index 1989]
 SYNONYMS                 Tixair [Merck Index 1989]
 SYNONYMS                 L-alpha-acetamido-beta-mercaptopropionic acid
                          [Merck Index 1989]
 SYNONYMS                 N-acetyl-3-mercaptoalanine [Merck Index 1989]
 SYNONYMS                 Mucosol [USP DI 1991]
 PROTOCOL ID NUMBERS      NIAID 91 I-68
 SECONDARY SOURCE ID      5052 [USAN 1996]
 SECONDARY SOURCE ID      NSC-111180 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Acetylcysteine is
                          deacetylated by the liver to cysteine and
                          subsequently metabolized. Recent studies have
                          demonstrated that human immunodeficiency
                          virus (HIV)-infected individuals have lower
                          levels of serum acid-soluble thiols, lower
                          levels of intracellular glutathione (GSH) in
                          peripheral blood mononuclear cells (PBMCs),
                          and that asymptomatic HIV-seropositive
                          individuals have dramatically reduced GSH
                          levels in lung epithelial lining fluid and in
                          blood plasma. These findings have been
                          related to the regulation of HIV replication
                          by demonstration that increased intracellular
                          thiol levels block the stimulation of HIV by
                          phorbol 12-myristate 13-acetate (PMA) and
                          tumor necrosis factor alpha (TNF-alpha).
                          TNF-alpha exerts some of its toxic effects by
                          stimulating production of reactive oxidative
                          intermediated (ROIs). PMA, which mimics
                          lymphokine activities, also stimulated ROI
                          production. Intracellular GSH protects cells
                          by scavenging ROIs; however, the
                          oxidant-buffering capacity of cellular GSH
                          can be overcome by excessive stimulation with
                          TNF-alpha. Thus drugs, like aceytlcysteine,
                          that replenish intracellular GSH may protect
                          against the toxic effects of TNF-alpha and
                          other agents that cause oxidative damage. The
                          latest findings show NAC not only increases
                          glutathione levels and suppresses HIV
                          replication (presumably via suppression of
                          the activation of transcription factor
                          NF-kappa B), but also is an effective
                          enhancer of T cell function and a remarkable
                          enhancer of growth. [Int Immunol 1993
                          Jan;5(1)] [AHFS Drug Information 1995] [Proc
                          Natl Acad Sci USA 1990 Roederer, et al,
                          87(6)]
 DISEASES STUDIED/TREATED Primary HIV infection [Pharmacology
                          1993;46(2)]
 CLASSIFICATION CODE      Antiretroviral [Int Conf AIDS 1992 Jul
                          19-24;8(2): (abstract no PoB 3013)]
 CLASSIFICATION CODE      Mucolytic [USAN 1996]
 OTHER MAJOR USES         Treatment of acetaminophen overdose to
                          protect against hepatotoxicity [USP DI 1995]
                          [AHFS Drug Information 1995]  Treatment of
                          various lung diseases requiring mucolysis
                          [USP DI 1995] [AHFS Drug Information 1995]
 SUBSTANCE INTERACTIONS   Interacts with activated charcoal. [USP DI
                          1991]
 ADVERSE EFFECTS          Appears to have a wide margin of safety.
                          Adverse effects may include stomatitis,
                          nausea (disagreeable odor may contribute),
                          vomiting, drowsiness, clamminess, rhinorrhea,
                          generalized urticaria, fever and chills,
                          elevations in liver function test results,
                          dermal eruptions, irritation of the tracheal
                          and bronchial tracts and hemoptysis, chest
                          tightness, bronchoconstriction, increased
                          airway obstruction, shortness of breath,
                          wheezing. [AHFS Drug Information 1995] [USP
                          DI 1995]
 CONTRAINDICATIONS        Monitor use closely in asthmatic patients, in
                          geriatric or debilitated patients with severe
                          respiratory insufficiency, in those with
                          conditions predisposing to gastric hemorrhage
                          including esophageal varices, peptic
                          ulceration and in nursing mothers. Use only
                          when clearly needed in pregnant women.
                          Contraindicated in patients hypersensitive to
                          the drug. [USP DI 1995] [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: N-acetyl derivative of the
                          naturally occurring amino acid L-cysteine
                          [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C5H9NO3S [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 163.20 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 109-110 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C36.79%, H5.56%,
                          N8.58%, O29.41%, S19.65% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Freely soluble in water and
                          alcohol [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Reducing agent which is
                          incompatible with oxidizing agents [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Solutions of acetylcysteine become
                          discolored and liberate hydrogen sulfide upon
                          contact with rubber and some metals
                          (particularly iron, nickel, copper), and/or
                          when subject to autoclaving [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: No reaction with glass, plastic,
                          aluminum, anodized aluminum, chromed metal,
                          tantalum, sterling sliver or stainless steel
                          [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Presence of light purple color in
                          solutions does not affect potency, but best
                          to use nonreactive material when
                          administering by nebulization [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: A white, crystalline
                          powder with a slight acetic ordor;
                          commercially available as aqueous solutions
                          of the sodium salt, prepared with the aid of
                          hydrogen sulfide [AHFS Drug Information 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 10 or 20 percent solution; or
                          10-20 percent solution diluted. [AHFS Drug
                          Information 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral (nebulization, direct
                          application, intratracheal instillation) and
                          intravenous. [USP DI 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Unopened vials should be stored at
                          15-30 C in tight containers. [USP DI 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Opened vials should be stored in a
                          refrigerator and discarded after 96 hours.
                          [USP DI 1995]
 MANUFACTURERS            Zambon
 REFERENCES               Clotet B, Gomez M, Ruiz L, Sirera G, Romeu J.
                          Lack of short-term efficacy of
                          N-acetyl-L-cysteine in human immunodeficiency
                          virus-positive patients with CD4 cell counts
                          < 250/mm3 [letter]. J Acquir Immune Defic Hum
                          Retrovirol. 1995 May 1;9(1):98-9.
 REFERENCES               Witschi A, Junker E, Schranz C, Speck RF,
                          Lauterburg BH. Supplementation of
                          N-acetylcysteine fails to increase
                          glutathione in lymphocytes and plasma of
                          patients with AIDS. AIDS Res Hum
                          Retroviruses. 1995 Jan;11(1):141-3.
 REFERENCES               Feregrino-Goyos M, Eid Lidt G, Gallegos Perez
                          H, Alvarado DR, Mino LD. AZT monotherapy
                          compared to AZT+DDC combined antiviral
                          therapy and AZT+DDC+NAC (100 patients each
                          group). Int Conf AIDS. 1994 Aug
                          7-12;10(1):208 (abstract no. PB0260).
 REFERENCES               Focaccia R, Cattapan A, Conceicao O, Buainain
                          R, Salaroli A, Focaccia MT. Response to
                          N-acetyl-L-cysteine on the CD4-CD8 system.
                          Int Conf AIDS. 1994 Aug 7-12;10(1):222
                          (abstract no. PB0319).
 REFERENCES               Droge W. Cysteine and glutathione deficiency
                          in AIDS patients: a rationale for the
                          treatment with N-acetyl-cysteine.
                          Pharmacology. 1993;46(2):61-5.
 REFERENCES               Clotat B, Gomez M, Romeu J, Sirera G, Condom
                          MJ, Costa J, Raventos A, Pont M. Effects on
                          surrogate markers of intravenous (i.v.)
                          N-acetyl-cysteine (NAC) in AIDS patients. Int
                          Conf AIDS. 1992 Jul 19-24;8(2):B89 (abstract
                          no PoB 3013).
 REFERENCES               Walker RE, Lane HC, Boenning CM, Polis MA,
                          Kovacs JA, Falloon J, Davey RT, Sussman H,
                          Gabel L, Correa-Coronas R, et al. The safety,
                          pharmacokinetics, and antiviral activity of
                          N-acetylcysteine in HIV-infected individuals.
                          Int Conf AIDS. 1992 Jul 19-24;8(1):Mo8
                          (abstract no. MoB 0022).
 REFERENCES               de Quay B, Malinverni R, Lauterburg BH.
                          Glutathione depletion in HIV-infected
                          patients: role of cysteine deficiency and
                          effect of oral N-acetylcysteine. AIDS. 1992
                          Aug;6(8):815-9.
 REFERENCES               Corso DM, Minor JR. Acetylcysteine in HIV
                          infection. Am J Hosp Pharm. 1992
                          Jan;49(1):175-6.
 REFERENCES               Roederer M, Ela SW, Staal FJ, Herzenberg LA,
                          Herzenberg LA. N-acetylcysteine: a new
                          approach to anti-HIV therapy. AIDS Res Hum
                          Retroviruses. 1992 Feb;(2):209-17.
 ENTRY MONTH              9103
 LAST REVISION DATE       951030
 

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