      Document 0240
 DOCN  DRG0240
 UNIQUE IDENTIFIER        DRG-0007
 NAME OF SUBSTANCE        Acetaminophen [USAN 1995]
 REGISTRY NUMBER          103-90-2
 STANDARD CHEMICAL NAME   N-(4-Hydroxyphenyl)acetanilide [USAN 1995]
 SYNONYMS                 Paracetamol [USAN 1995]
 SYNONYMS                 Acamol [Merck Index 1989]
 SYNONYMS                 Alpiny [Merck Index 1989]
 SYNONYMS                 Anhiba [Merck Index 1989]
 SYNONYMS                 Ben-u-ron [Merck Index 1989]
 SYNONYMS                 Bickie-mol [Merck Index 1989]
 SYNONYMS                 Dial-a-gesic [Merck Index 1989]
 SYNONYMS                 Doliprane [Merck Index 1989]
 SYNONYMS                 Temlo [Merck Index 1989]
 SYNONYMS                 Valadol [Merck Index 1989]
 SYNONYMS                 Cetadol [Merck Index 1989]
 SYNONYMS                 Acetalgin [Merck Index 1989]
 SYNONYMS                 Enelfa [Merck Index 1989]
 SYNONYMS                 Exdol [Merck Index 1989]
 SYNONYMS                 Finimal [Merck Index 1989]
 SYNONYMS                 Datril [Merck Index 1989]
 SYNONYMS                 Dirox [Merck Index 1989]
 SYNONYMS                 Nobedon [Merck Index 1989]
 SYNONYMS                 APAP [Merck Index 1989]
 SYNONYMS                 Tabalgin [Merck Index 1989]
 SYNONYMS                 Tempra [Merck Index 1989]
 SYNONYMS                 Calpol [Merck Index 1989]
 SYNONYMS                 Dymadon [Merck Index 1989]
 SYNONYMS                 Momentum [Merck Index 1989]
 SYNONYMS                 Naprinol [Merck Index 1989]
 SYNONYMS                 Panets   [Merck Index 1989]
 SYNONYMS                 Homoolan [Merck Index 1989]
 SYNONYMS                 Febrilix [Merck Index 1989]
 SYNONYMS                 Abensanil [Merck Index 1989]
 SYNONYMS                 Anaflon [Merck Index 1989]
 SYNONYMS                 Amadil [Merck Index 1983]
 SYNONYMS                 Eneril [Merck Index 1989]
 SYNONYMS                 Tralgon [Merck Index 1989]
 SYNONYMS                 Hedex [Merck Index 1989]
 SYNONYMS                 Pacemo [Merck Index 1989]
 SYNONYMS                 Panex [Merck Index 1989]
 SYNONYMS                 Panofen [Merck Index 1989]
 SYNONYMS                 Parmol [Merck Index 1989]
 SYNONYMS                 Tylenol [Merck Index 1989]
 SYNONYMS                 Panadol [Merck Index 1989]
 SYNONYMS                 Lyteca [Merck Index 1989]
 SYNONYMS                 Apamide [Merck Index 1989]
 SYNONYMS                 Tapar [Merck Index 1989]
 SYNONYMS                 Gelocatil [Merck Index 1989]
 SYNONYMS                 Korum [Merck Index 1989]
 SYNONYMS                 Paraspen [Merck Index 1989]
 SYNONYMS                 p-Hydroxyacetanilide [Merck Index 1989]
 SYNONYMS                 p-Acetamidophenol [Merck Index 1989]
 SYNONYMS                 p-Acetaminophenol [Merck Index 1989]
 SYNONYMS                 p-Acetylaminophenol [Merck Index 1989]
 SYNONYMS                 N-Acetyl-p-aminophenol [Merck Index 1989]
 SYNONYMS                 4'-Hydroxyacetanilide [Merck Index 1989]
 SYNONYMS                 Dafalgan [Merck Index 1989]
 SYNONYMS                 Disprol [Merck Index 1989]
 SYNONYMS                 Dolprone [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 032
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Not fully determined, but may
                          act (a) predominantly by inhibiting
                          prostaglandin synthesis in the central
                          nervous system or (b) to a lesser extent by
                          blocking pain-impulse generation through a
                          peripheral action; the peripheral action may
                          also be due to inhibition of prostaglandin
                          synthesis or to inhibition of synthesis or
                          actions of other substances that sensitize
                          pain receptors to mechanical or chemical
                          stimulation. Mechanism of antipyretic action
                          probably is due to the drug acting centrally
                          on the hypothalamic heat-regulating center to
                          produce peripheral vasodilation, resulting in
                          increased blood flow through the skin,
                          sweating, and heat loss; the centralization
                          probably involves inhibition of prostaglandin
                          synthesis in the hypothalamus. Oral doses of
                          the drug are rapidly and almost completely
                          absorbed; about 90-95 percent of the drug is
                          metabolized in the liver, principally via
                          conjugation with glucuronic acid, H2SO4, and
                          cysteine; an intermediate metabolite (which
                          may accumulate in overdose after the primary
                          metabolic pathways become saturated) is
                          hepatotoxic and possibly nephrotoxic. The
                          drug exhibits a half-life of 1-4 hours, which
                          does not change with renal failure but may be
                          prolonged in acute overdose, some forms of
                          hepatic disease, the elderly, and the
                          neonate, and may be somewhat shortened in
                          children. Peak plasma levels of 5-20 mcg/ml
                          from doses up to 650 mg are attained in 0.5-2
                          hours, with the peak effect attained in 1-3
                          hours and the duration of action lasting for
                          3-4 hours.  Elimination of the drug is
                          principally renal, as metabolites
                          (principally as conjugates) with about 3
                          percent of a dose excreted unchanged. [USP DI
                          1995]
 DISEASES STUDIED/TREATED Treatment of fever [USP DI 1995]
 CLASSIFICATION CODE      Analgesic [USAN 1995]
 CLASSIFICATION CODE      Antipyretic [USAN 1995]
 OTHER MAJOR USES         Treatment of fever, relief of minor aches,
                          pain, and headaches [USP DI 1995]
 SUBSTANCE INTERACTIONS   Acetaminophen may increase hepatotoxicity
                          risk when administered in chronic alcohol
                          abuse or with hepatotoxic medications or
                          hepatic enzyme inducers; the drug may
                          increase the anticoagulant effect of
                          coumarin- or indandione-derivative
                          anticoagulants; prolonged concurrent use of
                          the drug with a salicylate may increase the
                          risk of analgesic nephropathy, renal
                          papillary necrosis, end-stage renal disease,
                          and kidney and bladder cancer; prolonged
                          concurrent use with other nonsteroidal
                          anti-inflammatory analgesics may also
                          increase the risk of adverse renal effects;
                          Diflunisal may increase the plasma
                          Acetaminophen level by 50 percent, leading to
                          increased risk of Acetaminophen-induced
                          hepatotoxicity. [USP DI 1995]
 ADVERSE EFFECTS          Rare adverse events include agranulocytosis,
                          anemia, allergic dermatitis, renal colic,
                          renal failure, sterile pyruria and
                          thrombocytopenia. Overdose symptoms include
                          gastrointestinal upset, increased sweating
                          and hepatotoxicity. [USP DI 1995]
 CONTRAINDICATIONS        Should not be used by patients who have
                          demonstrated an intolerance to Acetaminophen.
                          Risk-benefit should be considered for
                          patients with alcoholism, hepatic disease,
                          viral hepatitis, or severe renal function
                          impairment. [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   DESCRIPTION: Acetamido-substituted phenol
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C8H9NO2 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 151.17 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C63.56%,
                          H6.00%, N9.27%, O21.17% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 169-170.5 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   DENSITY: 1.293 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in methanol, ethanol,
                          dimethyl-formamide, ethylene dichloride,
                          acetone, ethyl acetate [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Insoluble in petroleum ether,
                          pentane, benzene [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in 1 N NaOH [USP DI 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: UV max (ethanol): 250 nm
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White, odorless
                          crystalline powder with a slightly bitter
                          taste [PDR 1993]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Capsules, tablets, solutions and
                          suppositories. [USP DI 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral; rectal. [USP DI 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store below 40 C (104 F), preferably
                          at 15-30 C (59-86 F) in tight container and
                          protect from freezing. [USP DI 1995]
 MANUFACTURERS            Warner-Lambert Parke-Davis
 MANUFACTURERS            Lederle Laboratories
 MANUFACTURERS            Roxane Laboratories
 REFERENCES               Burger DM, Meenhorst PL, Underberg WJ, van de
                          Heijde JF, Koks CH, Beijnen JH. Short-term,
                          combined use of paracetamol and zidovudine
                          does not alter the pharmacokinetics of either
                          drug. Neth J Med. 1994 May;44(5):161-5.
 REFERENCES               Burger DM, Meenhorst PL, Koks CH, Beijnen JH.
                          Pharmacokinetics of zidovudine and
                          acetaminophen in a patient on chronic
                          acetaminophen therapy. Ann Pharmacother. 1994
                          Mar;28(3):327-30.
 REFERENCES               Gonzales M, Esteban A, Priego M, Boix V,
                          Portilla J, Perez-Mateo M. Acetaminophen (A)
                          metabolism in HIV infection. Int Conf AIDS.
                          1994 Aug 7-12;10(2):208 (abstract no.
                          PBO844).
 REFERENCES               Shriner K, Goetz MB. Severe hepatotoxicity in
                          a patient receiving both acetaminophen and
                          zidovudine. Am J Med. 1992 Jul;93(1):94-6.
 REFERENCES               Nicholas SW. Guidelines for the care of
                          children and adolescents with HIV infection.
                          Management of the HIV-positive child with
                          fever. J Pediatr. 1991 Jul;119(1 (Pt
                          2)):S21-4.
 REFERENCES               Sattler FR, Ko R, Antoniskis D, Shields M,
                          Cohen J, Nicoloff J, Leedom J, Koda R.
                          Acetaminophen does not impair clearance of
                          zidovudine. Ann Intern Med. 1991 Jun
                          1;114(11):937-40.
 REFERENCES               Steffe EM, King JH, Inciardi JF, Flynn NF,
                          Goldstein E, Tonjes TS, Benet LZ. The effect
                          of acetaminophen on zidovudine metabolism in
                          HIV-infected patients. J Acquir Immune Defic
                          Syndr. 1990;3(7):691-4.
 REFERENCES               Steffe E, Inciardi J, King J, Flynn N,
                          Goldstein E, Tanjes T. Analysis of the effect
                          of acetaminophen on zidovudine
                          pharmacokinetics in HIV infected patients.
                          Int Conf AIDS. 1989 Jun 4-9;5:560 (abstract
                          no. M.C.P.113).
 REFERENCES               Pazin GJ, Ptachcinski RJ, Sheehan M, Ho M.
                          Interactive pharmacokinetics of zidovudine
                          and acetaminophen. Int Conf AIDS. 1989 Jun
                          4-9;5:278 (abstract no. M.B.P.338).
 ENTRY MONTH              8906
 LAST REVISION DATE       960501
 

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