      Document 0133
 DOCN  DRG0133
 UNIQUE IDENTIFIER        DRG-0114
 NAME OF SUBSTANCE        Ranitidine hydrochloride [USAN 1996]
 REGISTRY NUMBER          66357-59-3
 STANDARD CHEMICAL NAME   N(2-(((5-((dimethylamino)methyl)-2-furanyl)me-
                          thyl)thio)
                          ethyl)-N'-methyl-2-nitro-1,1-ethenediamine,
                          hydrochloride [USAN 1996]
 SYNONYMS                 Zantac [USAN 1996]
 SYNONYMS                 Azantac [Merck Index 1989]
 SYNONYMS                 Melfax [Merck Index 1989]
 SYNONYMS                 Noctone [Merck Index 1989]
 SYNONYMS                 Raniben [Merck Index 1989]
 SYNONYMS                 Ranidil [Merck Index 1989]
 SYNONYMS                 Raniplex [Merck Index 1989]
 SYNONYMS                 Sostril [Merck Index 1989]
 SYNONYMS                 Taural [Merck Index 1989]
 SYNONYMS                 Terposen [Merck Index 1989]
 SYNONYMS                 Trigger [Merck Index 1989]
 SYNONYMS                 Ulcex [Merck Index 1989]
 SYNONYMS                 Ultidine [Merck Index 1989]
 SYNONYMS                 Zantic [Merck Index 1989]
 SYNONYMS                 Zantidon [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 136
 PROTOCOL ID NUMBERS      FDA 135A
 SECONDARY SOURCE ID      AH 19065 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Competitive, reversible
                          inhibitor of the action of histamine at the
                          histamine H2-receptors, including receptors
                          on the gastric cells. In one study ranitidine
                          was shown to improve spontaneous and in vitro
                          interleukin-2 and interferon-alpha-stimulated
                          natural killer cell activity. Furthermore
                          T-cell blastogenesis to phytohemagglutinin
                          stimulation and soluble interleukin-2
                          receptors in serum increased. However, both
                          of these reported results were only a slight
                          improvement from the control group. [PDR
                          1995] [J Acquir Immune Defic Syndr 1991;4(6)]
 DISEASES STUDIED/TREATED Enhancement of immune function in HIV
                          infection / enhancement of drug effects
                          [Antimicro Agents Chemother 1992 Oct;36(10)]
                          [AmFAR Tx Dir 1995;7(4)]
 CLASSIFICATION CODE      Histamine (H2) receptor antagonist [USAN
                          1996]
 CLASSIFICATION CODE      Immunomodulator [J Acquir Immune Defic Syndr
                          1991;4(6)]
 OTHER MAJOR USES         Short-term treatment of active duodenal
                          ulcer; maintenance therapy for duodenal
                          ulcers; pathological hypersecretory
                          conditions; short-term treatment of active,
                          benign gastric ulcer; treatment of
                          gastroesophageal reflux disease (GERD) [PDR
                          1995]
 SUBSTANCE INTERACTIONS   May enhance absorption of didanosine (ddI).
                          Administration of didanosine 2 hours after
                          ranitidine will result in a minor increase in
                          the bioavailability of didanosine. Ranitidine
                          absorption may be decreased by antacids and
                          propantheline bromide. Smoking decreases the
                          efficacy of the drug. Increased or decreased
                          prothrombin times have been reported when
                          ranitidine was administered with coumarin
                          anticoagulants. Theophylline plasma clearance
                          has been decreased by concomitant ranitidine.
                          [Antimicro Agents Chemother 1992 Oct; 36(10)]
                          [Int Conf AIDS Jun 20-23;6(3):(abstract no.
                          S.B. 470)] [AHFS Drug Information 1995]
 ADVERSE EFFECTS          Adverse effects may include headache,
                          sometimes severe. Other reactions rarely
                          reported include CNS effects such as malaise,
                          dizziness, agitation and confusion. Cardiac
                          arrhythmias, constipation, diarrhea, nausea
                          and vomiting, arthralgias, myalgias and rash
                          have also been reported. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with known
                          sensitivity to drug. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A histamine H2-receptor
                          antagonist [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORM: C13H22N4O3S.HCl [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 350.87 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 133-134 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C49.66%, H7.05%,
                          N17.82%, O15.27%, S10.20% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: Ranitidine injection is stable for
                          up to 48 hours at room temperature when added
                          to or diluted with most IV solutions [AHFS
                          Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Pharmacy IV admixtures prepared
                          from the bulk package should be used within
                          24 hours [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Freely soluble in water and
                          acetic acid, soluble in methanol, sparingly
                          soluble in ethanol, practically insoluble in
                          chloroform [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: pKa 8.2 and 2.7 [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to pale yellow,
                          granular powder with a slightly bitter taste
                          and sulfur-like odor [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: The injectable solution
                          is a clear, colorless to yellow liquid [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: IV injection, oral
                          ingestion. [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Capsules and tablets (150 mg and
                          300 mg), syrup (75 mg/5 ml), granules (150
                          mg), injections (0.5 mg/ml and 25 mg/ml),
                          infusion packs and bulk pharmacy package.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store single dose vials and bulk
                          pharmacy packages between 2-4 C. Store
                          flexible plastic containers between 2-25 C.
                          Protect all injectable solutions from light.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store capsules between 2-25 C, store
                          tablets between 15-30 C, store granules
                          between 2-30 C and store syrup between 4-25 C
                          and protect from light [PDR 1995]
 MANUFACTURERS            Glaxo Wellcome
 REFERENCES               Smith KC. Ranitidine useful in the management
                          of psoriasis in a patient with acquired
                          immunodeficiency syndrome [letter]. Int J
                          Dermatol. 1994 Mar;33(3):220-1.
 REFERENCES               Knupp CA, Graziano FM, Dixon RM, Barbhaiya
                          RH. Pharmacokinetic-interaction study of
                          didanosine and ranitidine in patients
                          seropositive for human immunodeficiency
                          virus. Antimicrob Agents Chemother. 1992
                          Oct;36(10):2075-9.
 REFERENCES               Hartman NR, Yarchoan R, Pluda JM, Thomas RV,
                          Wyvill KM, Flora KP, Broder S, Johns DG.
                          Pharmacokinetics of 2',3'-dideoxyinosine in
                          patients with severe human immunodeficiency
                          infection. II. The effects of different oral
                          formulations and the presence of other
                          medications. Clin Pharmacol Ther. 1991
                          Sep;50(3):278-85.
 REFERENCES               Neilson HJ, Svenningsen A, Moesgaard F,
                          Georgsen J, Pedersen C, Mathiesen L,
                          Dickmeiss E, Nielsen JO, Kehlet H. Ranitidine
                          improves certain cellular immune responses in
                          asymptomatic HIV-infected individuals. J
                          Acquir Immune Defic Syndr. 1991;4(6):577-84.
 REFERENCES               Hartman NR, Yarchoan R, Thomas RV, Pluda JM,
                          Marczyk KS, Broder S, Johns DG. Effect of
                          different oral preparations and presence of
                          other medications on the pharmacokinetics of
                          2',3'-dideoxyinosine. Int Conf AIDS. 1990 Jun
                          20-23;6(3):203 (abstract no. S.B.470).
 ENTRY MONTH              9105
 LAST REVISION DATE       960612
 

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