      Document 0190
 DOCN  DRG0190
 UNIQUE IDENTIFIER        DRG-0057
 NAME OF SUBSTANCE        Oxazepam [USAN 1996]
 REGISTRY NUMBER          604-75-1
 STANDARD CHEMICAL NAME   7-Chloro-1,3-
                          dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazep-
                          in-2-one [USAN 1996]
 SYNONYMS                 Abboxampam [Merck Index 1989]
 SYNONYMS                 Adumbran [Merck Index 1989]
 SYNONYMS                 Aplakil [Merck Index 1989]
 SYNONYMS                 Azutranguil [Merck Index 1989]
 SYNONYMS                 Bonare [Merck Index 1989]
 SYNONYMS                 Durazepam [Merck Index 1989]
 SYNONYMS                 Enidrel [Merck Index 1989]
 SYNONYMS                 Hilong [Merck Index 1989]
 SYNONYMS                 Isodin [Merck Index 1989]
 SYNONYMS                 Lederpam [Merck Index 1989]
 SYNONYMS                 Limbial [Merck Index 1989]
 SYNONYMS                 Nesontil [Merck Index 1989]
 SYNONYMS                 Noctazepam [Merck Index 1989]
 SYNONYMS                 Oxanid [Merck Index 1989]
 SYNONYMS                 Oxa-Puren [Merck Index 1989]
 SYNONYMS                 Praxiten [Merck Index 1989]
 SYNONYMS                 Propax [Merck Index 1989]
 SYNONYMS                 Quilibrex [Merck Index 1989]
 SYNONYMS                 Rondar [Merck Index 1989]
 SYNONYMS                 Serax [PDR 1993]
 SYNONYMS                 Serenal [Merck Index 1989]
 SYNONYMS                 Serenid [Merck Index 1989]
 SYNONYMS                 Serepax [Merck Index 1989]
 SYNONYMS                 Seresta [Merck Index 1989]
 SYNONYMS                 Sigacalm [Merck Index 1989]
 SYNONYMS                 Sobril [Merck Index 1989]
 SYNONYMS                 Tazepam [Merck Index 1989]
 SYNONYMS                 Uskan [Merck Index 1989]
 SYNONYMS                 Zaxopam [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 124
 SECONDARY SOURCE ID      Wy-3498 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: The exact sites and mode of
                          actions of the benzodiazepines have not been
                          fully elucidated; effects appear to be
                          mediated through the inhibitory
                          neurotransmitter gamma-aminobutyric acid
                          (GABA). The drugs appear to act at the
                          limbic, thalamic and hypothalamic levels of
                          the CNS producing anxiolytic, sedative,
                          hypnotic, skeletal muscle relaxant, and
                          anticonvulsive effects. They are capable of
                          producing all levels of CNS depression - from
                          mild sedation to hyponosis to coma. Capsule,
                          tablet and suspension of oxazepam (single 30
                          mg dose) were equivalent in extent of
                          absorption and produced plasma levels of 450
                          ng/ml 3 hours after dosing. The mean
                          elimination half-life was approx. 8.2 hours.
                          The single major inactive metabolite in man,
                          a glucuronide, was excreted in the urine. The
                          acute oral Ld50 in mice was 5000 mg/kg. [PDR
                          1995]
 DISEASES STUDIED/TREATED AIDS-related anxiety [NIAID ACTG 124]
 CLASSIFICATION CODE      Anxiolytic [Merck Index 1989]
 CLASSIFICATION CODE      Minor tranquilizer [USAN 1996]
 OTHER MAJOR USES         Indicated for adjunctive management of
                          anxiety associated with mental depression and
                          relief of acute alcohol withdrawal symptoms
                          [PDR 1995]
 SUBSTANCE INTERACTIONS   Additive CNS depression may occur when
                          benzodiazepines are given with other CNS
                          depressants, including other antidepressants
                          and alcohol. Concurrent administration of
                          benzodiazepines with disulfiram may result in
                          some inhibition of metabolism of the former.
                          Benzodiazepines should be given with caution
                          to patients on levodopa. There have been
                          reports of impaired motor functions in
                          patients on benzodiazepines and tricyclic
                          antidepressants. Antacids such as calcium or
                          magnesium hydroxides may decrease the rate of
                          GI absorption of some benzodiazepines.
                          Limited evidence suggests that some
                          benzodiazepines may reduce renal excretion of
                          digoxin resulting in increased plasma
                          half-life and possible toxicity of the
                          digoxin. [AHFS Drug Information 1995]
 ADVERSE EFFECTS          The necessity for discontinuation of therapy
                          due to undesirable effects has been rare.
                          Transient mild drowsiness is commonly seen in
                          the first few days of therapy. If it
                          persists, the dosage should be reduced. In
                          few instances, dizziness, vertigo, headache,
                          and rarely syncope have occurred either alone
                          or together with drowsiness. Mild paradoxical
                          reactions, i.e., excitment, stimulation of
                          affect, have been reported in psychiatric
                          patients; these reactions may be secondary to
                          relief of anxiety and usually appear in the
                          first 2 weeks of therapy. Rare reactions:
                          skin rashes, nausea, lethargy, edema, slurred
                          speech, tremors, altered libido, leukopenia,
                          hepatic dysfunction including jaundice, and
                          ataxia. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with history of
                          previous hypersensitivity reaction to
                          oxazepam or in patients with psychoses. As
                          with other central nervous system (CNS)
                          acting drugs, patients should be cautioned
                          against driving automobiles or operating
                          dangerous machinery until it is known that
                          they do not become drowsy or dizzy on
                          oxazepam therapy. Patients should be warned
                          that the effects of alcohol or other
                          CNS-depressant drugs may be additive to those
                          of oxzepam, possibly requiring adjustment of
                          dosage or elimination of such agents. Not
                          advised in pregnant women. An increased risk
                          of congenital malformations associated with
                          the use of minor tranquilizers during the
                          first trimester of pregnancy has been
                          suggested. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The first of a new series
                          of chemical compounds called the
                          3-hydroxybenzodiazepinones [PDR 1995]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C62.83%; H3.87%;
                          Cl12.37%; N9.77%; O11.16% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C15H11C1N2O2 [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 286.74 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 205 - 206 C. Soluble in
                          alcohol, chloroform, dioxane. Practically
                          insoluble in water [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Creamy white or pale
                          yellow powder [AHFS Drug Information 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Capsules and tablets. Controlled
                          substance in the U.S. [AHFS Drug Information
                          1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Usual adult dose for antianxiety
                          is 10 to 15 mg 3 or 4 times a day; as a
                          sedative-hypnotic and for alchohol withdrawal
                          the dose is 15-30 mg 3 or 4 times a day.
                          [AHSF Drug Information 1995
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Strengths available are 10 mg,
                          15 mg, and 30 mg. [AHFS Drug Information
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral administration of
                          capsules or tablets. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE INSTRUCTION: Store below 40 C (104
                          F), preferably between 15-30 C (59-86 F), in
                          a well-closed container. [AHFS Drug
                          Information 1995]
 MANUFACTURERS            Wyeth-Ayerst
 REFERENCES               Storm G, Oosterhuis B, Sollie FA, Visscher
                          HW, Sommer W, Beitinger H, Jonkman JH. Lack
                          of pharmacokinetic interaction between
                          vinpocetine and oxazepam. Br J Clin
                          Pharmacol. 1994 Aug;38(2):143-6.
 REFERENCES               Mole L, Israelski D, Bubp J, O'Hanley P,
                          Merigan T, Blaschke T. Pharmacokinetics of
                          zidovudine alone and in combination with
                          oxazepam in the HIV infected patient. J
                          Acquir Immune Defic Syndr. 1993 Jan;
                          6(1):56-60.
 REFERENCES               Landon JF, Sher KJ, Shah JH. Effects of
                          oxazepam on anxiety: implications for Fowles'
                          psychophysiological interpretation of Gray's
                          model. Psychopharmacology (Berl).
                          1993;113(1):137-43.
 REFERENCES               Stuppaeck CH, Pycha R, Miller C, Whitworth
                          AB, Oberbauer H, Fleischhacker WW.
                          Carbamazepine versus oxazepam in the
                          treatment of alcohol withdrawal: a
                          double-blind study. Alcohol Alcohol. 1992
                          Mar:27(2):153-8.
 REFERENCES               Herz LR, Volicer L, Ross V, Rheaume Y. A
                          single-case-study method for treating
                          resistiveness in patients with Alzheimers's
                          disease. Hosp Community Psychiatry. 1992
                          Jul;43(7):720-4.
 REFERENCES               Herz LR, Volicer L, Ross V, Rheaume Y.
                          Pharmacotherapy of agitation in dementia
                          [letter; comment]. Am J Psychiatry. 1992
                          Dec;149(12):1757-8.
 REFERENCES               Sheikh JI. Anxiety disorders and their
                          treatment. Clin Geriatr Med. 1992
                          May;8(2):411-26.
 REFERENCES               Rimon R, Kultalahti ER, Kalli A, Koskinen T,
                          Lepola U, Naarala M, Tick E. Alprazolam and
                          oxazepam in the treatment of anxious
                          out-patients with depressive symptoms: a
                          double-blind multicenter study.
                          Pharmacopsychiatry. 1991 May;24(3):81-4.
 REFERENCES               Ansseau M, Papart P, Gerard MA, von Frenckell
                          R, Franck G. Controlled comparison of
                          buspirone and oxazepam in generalized
                          anxiety. Neuropsychobiology.
                          1990-91;24(2):74-8.
 REFERENCES               Strand M, Hetta J, Rosen A, Sorensen S,
                          Malmstrom R, Fabian C, Marits K, Vetterskog
                          K, Liljestrand AG, Hegen C. A double-blind,
                          controlled trial in primary care patients
                          with generalized anxiety: a comparison
                          between buspirone and oxazepam. J Clin
                          Psychiatry. 1990 Sep;51 Suppl:40-5.
 ENTRY MONTH              9006
 LAST REVISION DATE       951128
 

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