      Document 0176
 DOCN  DRG0176
 UNIQUE IDENTIFIER        DRG-0071
 NAME OF SUBSTANCE        Ceftriaxone sodium [USAN 1996]
 REGISTRY NUMBER          74578-69-1
 RELATED REGISTRY NUMBER  73384-59-5
 RELATED REGISTRY NUMBER  130091-53-1
 STANDARD CHEMICAL NAME   5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxy-
                          lic acid,
                          7-(((2-amino-4-thiazolyl)(methoxyimino)acetyl-
                          )amino)8-oxo-3
                          -(((1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2-
                          ,4-triazin-3- yl)thio)methyl)-, disodium
                          salt, (6R-(6alpha,7beta(Z)))-, hydrate (2:7)
                          [USAN 1996]
 SYNONYMS                 Rocephin [PDR 1995]
 SYNONYMS                 (6R,7R)-7-2-[2-(2-amino-4-thiazolyl)glyoxylam-
                          ido]-3-[[2,5-didehydro-6-hydroxy-2-methyl-5-o-
                          xo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carb-
                          oxylic acid 7(2)-(Z)-(O-methyloxime) [Merck
                          Index 1989]
 SYNONYMS                 RoceFin [Merck Index 1989]
 PROTOCOL ID NUMBERS      FDA 019A
 PROTOCOL ID NUMBERS      NIAID ACTG 145
 SECONDARY SOURCE ID      Ro-13-9904 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Average plasma concentrations
                          of ceftriaxone following a single 30-minute
                          intravenous infusion of a 0.5, 1, or 2 g dose
                          after 30 minutes were 82, 151, and 257
                          mcg/ml, respectively (for intramuscular
                          administration of a single 0.5 or 1 g dose,
                          the concentrations were 30 and 40 mcg/ml
                          respectively). The drug was completely
                          absorbed following intramuscular
                          administration with mean maximum plasma
                          levels occurring between 2-3 hours after
                          dosing. Multiple intravenous or intramuscular
                          doses ranging from 0.5-2 g at 12-24 hour
                          intervals resulted in 15-36% accumulation of
                          the drug above single dose values. High
                          levels of the drug appear in urine, declining
                          to low levels after 24-48 hours. A total of
                          33-67% of a ceftriaxone dose was excreted in
                          urine as unchanged drug, with the remainder
                          secreted in the bile and ultimately found in
                          the feces as microbiologically inactive
                          compounds. After a 1 g intravenous dose, mean
                          levels of the drug found from 1-3 hours after
                          dosing in the gallbladder bile, common duct
                          bile, cystic duct bile, gallbladder wall, and
                          concurrent plasma were 581, 788, 898, 78.2,
                          and 62.1 mcg/ml. Over a 0.15-3 g dose range
                          in healthy adult subjects drug elimination
                          half-life ranged from 5.8-8.7 hours; apparent
                          volume of distribution from  5.78-13.51;
                          plasma clearance from 0.58-1.45/hour; and
                          renal clearance from 0.32-0.73 l/hour.
                          Ceftriaxone is reversibly bound to human
                          plasma proteins, and the binding decreased
                          from 95% bound at plasma levels of less than
                          25 mcg/ml to 85% bound at 300 mcg/ml. After
                          3-4 hours following a 50 mg/kg intravenous
                          dose, the mean peak plasma level (mcg/ml),
                          elimination half-life (hours), plasma
                          clearance (ml/hour/kg), volume of
                          distribution (ml/kg), and cerebrospinal fluid
                          level (mcg/ml) in pediatric patients with
                          bacterial meningitis were 216, 4.6, 49, 338,
                          and 5.6, respectively (following a 75 mg/kg
                          intravenous dose the respective values were
                          275, 4.3, 60, 373, and 6.4). Relative to
                          healthy adults, the pharmacokinetics of
                          ceftriaxone were only minimally altered in
                          elderly subjects and in patients with renal
                          impairment or hepatic dysfunction.
                          Ceftriaxone was not significantly removed
                          from the plasma by hemodialysis. Plasma
                          elimination rates may be markedly reduced in
                          some patients, requiring monitoring for any
                          necessary dosage adjustments. [PDR 1995]
 DISEASES STUDIED/TREATED An antibiotic under investigation as an
                          alternative to penicillin for the treatment
                          of neurosyphilis [AmFAR Tx Dir 1995;7(4)]
                          [AHFS Drug Information 1995]
 DISEASES STUDIED/TREATED Single dose chancroid therapy may be less
                          effective in HIV patients and other
                          anti-infectives should be used [AmFAR Tx Dir
                          1995;7(4)] [AHFS Drug Information 1995]
 CLASSIFICATION CODE      Antimicrobial [PDR 1993]
 OTHER MAJOR USES         Treatment of infections of the lower
                          respiratory tract, skin, bone, joints,
                          intra-abdominal region, urinary tract; used
                          in gonorrhea, meningitis and bacterial
                          septicemia [PDR 1995]
 ADVERSE EFFECTS          May cause local pain or tenderness at site of
                          injection, phlebitis, rash, pruritus, fever,
                          chills, eosinophilia, thrombocytosis,
                          leukopenia, anemia, neutropenia, lymphopenia,
                          thrombocytopenia, prothrombin time
                          prolongation, diarrhea, nausea, vomiting,
                          dysgeusia, headache, dizziness, moniliasis,
                          vaginitis, diaphoresis, flushing. Rarely
                          observed reactions include leukocytosis,
                          lymphocytosis, monocytosis, basophilia,
                          jaundice, gallbladder sludge, glycosuria,
                          hematuria, anaphylaxis, bronchospasm, serum
                          sickness, abdominal pain, colitis,
                          flatulence, dyspepsia, palpitations, and
                          epistaxis. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated for patients with known
                          allergy to the cephalosporin class of
                          antibiotics. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Semisynthetic 3rd
                          generation cephalosporin derivative [PDR
                          1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C18H16N8Na2O7S3.3.5H2O
                          [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 661.61 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C38.98%, H3.27%,
                          N20.21%, O20.20%, S17.34% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: > 155 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: The commercial product, Rocephin,
                          should not be physically mixed with or piggy
                          backed into solutions containing other
                          antimicrobial drugs or into diluent
                          solutions, other than those recommended by
                          the manufacturer [PDR 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Do not refreeze thawed solutions
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Water; approximately 40 g/100 ml;
                          sparingly soluble in methanol; very slightly
                          soluble in ethanol [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to
                          yellowish-orange crystalline powder [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Vials of powder containing 250
                          mg, 500 mg, 1 g, and 2 g of drug. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous or
                          intramuscular injection. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Sterile powder should be stored at
                          room temperature or below and protected from
                          light. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: The reconstituted IM solution
                          remains stable for varying periods of time
                          depending on the diluent and the temperature.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Room temperature solutions are
                          stable from 24 hours to 3 days. Refrigerated
                          solutions are stable from 3-10 days. [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Reconstituted IV solution stability
                          varies from 3 days at room temperature to 10
                          days at refrigerator temperatures. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Reconstituted solutions remain
                          stable for 26 weeks when stored in frozen
                          state (below -20 C). Once thawed excess
                          solution should be thrown away. [PDR 1995]
 MANUFACTURERS            Hoffmann-La Roche
 REFERENCES               Sands M, Markus A. Lues maligna, or
                          ulceronodular syphilis, in a man infected
                          with human immunodeficiency virus: case
                          report and review. Clin Infect Dis. 1995
                          Feb;20(2):387-90.
 REFERENCES               Merianos A, Gilles M, Chuah J. Ceftriaxone in
                          the treatment of chronic donovanosis in
                          central Australia. Genitourin Med 1994
                          Apr;70(2):74-9.
 REFERENCES               Adjei O. Surveillance of Neisseria gonorrhoea
                          in Kumasi, 1989-1992. Int Conf AIDS. 1994 Aug
                          7-12;10(2):292 (abstract no. PC0553).
 REFERENCES               Schutze GE, Landers S. Management of infants
                          born women with sexually transmitted
                          diseases. Am Fam Physician. 1994 Nov
                          15;50(7):1479-86.
 REFERENCES               Tyndall M, Malisa M, Plummer FA, Ombetti J,
                          Ndinya-Achola JO, Ronald AR. Ceftriaxone no
                          longer predictably cures chancroid in Kenya.
                          J Infect Dis. 1993 Feb;167(2):469-71.
 REFERENCES               Njagi E, Temmeran M, Nagelkerke N,
                          Ndinya-Achola JO, Plummer F, Meheus A. Mass
                          antimicrobial treatment in pregnancy: a
                          randomized placebo controlled trial in a
                          population with high rates of sexually
                          transnitted diseases. Int Conf AIDS. 1993 Jun
                          6-11;9(1):458 (abstract no. PO-B23-1935).
 REFERENCES               Dowell ME, Ross PG, Musher DM, Cate TR,
                          Baughn RE. Response of latent syphilis or
                          neurosyphilis to ceftriaxone therapy in
                          persons infected with human immunodeficiency
                          virus. Am J Med. 1992 Nov;93(5):481-8.
 REFERENCES               Grossi E, Bucceri A, Magnani M, Melidoni R,
                          Polvani F. HIV seropositivity and Caesarean
                          section. Int Conf AIDS. 1991 Jun
                          16-21;7(2):192 (abstract no. W.B.2043).
 REFERENCES               Bryan JP, Hira SK, Brady W, Luo N, Mwale C,
                          Mpoko G, Krieg R, Siwiwaliondo E, Reichart C,
                          Waters C, et al. Oral ciprofloxacin versus
                          ceftriaxone for the treatment of urethritis
                          from resistant Neisseria gonorrhoeae in
                          Zambia. Antimicrob Agents Chemother. 1990
                          May;34(5):819-22.
 REFERENCES               Judson FN. Gonorrhea. Med Clin North Am. 1990
                          Nov;74(6):1353-66.
 ENTRY MONTH              8911
 LAST REVISION DATE       951024
 

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