      Document 0048
 DOCN  DRG0048
 UNIQUE IDENTIFIER        DRG-0199
 NAME OF SUBSTANCE        Capreomycin sulfate [USAN 1996]
 REGISTRY NUMBER          1405-37-4
 STANDARD CHEMICAL NAME   Capreomycin sulfate [USAN 1996]
 SYNONYMS                 Capastat Sulfate [USAN 1996]
 SYNONYMS                 Caprocin [USAN 1996]
 SYNONYMS                 Capostatin [Merck Index 1989]
 SYNONYMS                 Ogostal [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 238
 SECONDARY SOURCE ID      34977 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Active against strains of
                          Mycobacterium tuberculosis found in humans.
                          Not absorbed in significant quantities from
                          the gastrointestinal tract and must be
                          administered parenterally. In previous
                          studies using 1 g capreomycin (IM), peak
                          serum concentrations were achieved 1 to 2
                          hours after administration, and average peak
                          levels reached were 28 and 32 mcg/ml,
                          respectively. In normal volunteers, 52
                          percent of the drug was excreted in the urine
                          within 12 hours. Frequent cross-resistance
                          occurs between capreomycin and viomycin. No
                          cross-resistance has been observed between
                          capreomycin and isoniazid, aminosalicylic
                          acid, cycloserine, streptomycin, ethionamide,
                          or ethambutol. [PDR 1995] [AHFS Drug
                          Information 1995]
 DISEASES STUDIED/TREATED Used as second-line therapy in combination
                          with other antituberculosis drugs for
                          pulmonary tuberculosis [PDR 1995]
 CLASSIFICATION CODE      Antibacterial [USAN 1996]Antibacterial agent
                          [USAN 1993]
 SUBSTANCE INTERACTIONS   Since there is some evidence that nephrotoxic
                          and/or ototoxic effects may be additive, the
                          concurrent or sequential use of capreomycin
                          and other nephrotoxic and/or ototoxic drugs
                          including aminoglycosides, colistin,
                          polymyxin B, and vancomycin should be
                          avoided. [AHFS Drug Information 1995]
 ADVERSE EFFECTS          Adverse effects include nephrotoxicty,
                          electrolyte disturbances resembling Bartter's
                          syndrome, ototoxcicity, abnormal liver
                          function tests, leukocytosis and leukopenia,
                          pain and induration at injection site,
                          excessive bleeding at injection site, sterile
                          abscesses, urticaria, and maculopapular skin
                          rashes. [PDR 1995]
 CONTRAINDICATIONS        Should be used with extreme caution in
                          patients with renal insufficiency or auditory
                          impairment. Contraindicated in patients who
                          are hypersensitive to capreomycin. Safe use
                          in children has not been established. Should
                          be used in pregnant women only if the
                          potential benefits outweigh the potential
                          risk to the fetus. [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Cyclic peptide antibiotic
                          similar to viomycin; produced by Streptomyces
                          capreolus; complex of four microbiologically
                          active components which have been
                          characterized in part [Merck Index 1989] [PDR
                          1995]DRUG DESCRIPTION: The 4-amino derivative
                          of a group of hydroxybenzoic acids.
                          Bacteriostatic agent. [MeSH; NIAID ACTG 238]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C25H44N14O8.2H2SO4 [Merck
                          Index 1989]MOLECULAR FORMULA: C7H7NO3 [USAN
                          1993]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water [PDR
                          1995]MOLECULAR WEIGHT: 153.14 [USAN 1993]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Almost colorless in
                          complete solution [PDR 1995]MELTING POINT:
                          150-151 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMP: C54.90%, H4.61%, N9.15%,
                          O31.34% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water, alcohol, dilute
                          nitric acid, dilute sodium hydroxide.
                          Slightly soluble in ether. Practically
                          insoluble in benzene. [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: Unstable in a moist environment
                          and will discolor [NIAID ACTG 238]
 CHEMICAL/PHYSICAL DATA   pKa: 3.25 [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 10 ml vials. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intramuscular. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: May be stored as reconstituted
                          solution for 48 hr at room temperature and
                          for up to 14 days under refrigeration. [PDR
                          1995]
 MANUFACTURERS            Eli Lilly and Company
 REFERENCES               Thiara AS, Cundliffe E. Analysis of two
                          capreomycin-resistance determinants from
                          Streptomyces capreolus and characterization
                          of the action of their products. Gene 1995
                          Dec 29;167(1-2):121-6.
 REFERENCES               Le Conte P, Le Gallou F, Potel G, Struillou
                          L, Baron D, Drugeon HB. Pharmacokinetics,
                          toxicity, and efficacy of liposomal
                          capreomycin in disseminated Mycobacterium
                          avium beige mouse model. Antimicrob Agents
                          Chemother; VOL 38,ISS 12,1994,P2695-701.
 REFERENCES               Wank H, Rogers J, Davies J, Schroeder R.
                          Peptide antibiotics of the tuberactinomycin
                          family as inhibitors of group I intron RNA
                          splicing. J Mol Biol; VOL 236,ISS
                          4,1994,P1001-10.
 REFERENCES               Nolan CM, Sandblom RE, Thummel KE, Slattery
                          JT, Nelson SD. Hepatotoxicity associated with
                          acetaminophen usage in patients receiving
                          multiple drug therapy for tuberculosis.
                          Chest; VOL 105,ISS 2,1994,P408-11.
 REFERENCES               Salfinger M, Gross W, Kornblum J, Laszlo A,
                          Pfyffer G, Roberts G, Siddiqi S. Radiometric
                          susceptibility testing of Mycobacterium
                          tuberculosis against second-line drugs. Abstr
                          Gen Meet Am Soc Microbiol. 1994;94:197
                          (abstract no. U-138).
 REFERENCES               Weltman AC, Rose DN. Tuberculosis
                          susceptibility patterns, predictors of
                          multidrug resistance, and implications for
                          initial therapeutic regimens at a New York
                          City hospital. Arch Intern Med. 1994 Oct
                          10;154(19):2161-7.
 REFERENCES               Peloquin CA. Pharmacology of the
                          antimycobacterial drugs. Med Clin North Am.
                          1993 Nov;77(6):1253-62.
 REFERENCES               Cowling P, Glover S, Reeves DS. Mycobacterium
                          malmoense type II bacteraemia contributing to
                          death in a patient with AIDS. Int J STD AIDS.
                          1992 Nov-Dec;3(6):445-6.
 REFERENCES               Heifets L, Lindholm-Levy P. Comparison of
                          bactericidal activities of streptomycin,
                          amikacin, kanamycin, and capreomycin against
                          Mycobacterium avium and M. tuberculosis.
                          Antimicrob Agents Chemother. 1989
                          Aug;33(8):1298-301.
 ENTRY MONTH              9403
 LAST REVISION DATE       960417
 

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