      Document 0059
 DOCN  DRG0059
 UNIQUE IDENTIFIER        DRG-0188
 NAME OF SUBSTANCE        Paromomycin sulfate [USAN 1996]
 REGISTRY NUMBER          1263-89-4
 STANDARD CHEMICAL NAME   D-Streptamine,
                          0-2-amino-2-deoxy-alpha-D-glucopyranosyl-(1
                          to
                          4)-O-[O-2,6-diamino-2,6-dideoxy-beta-L-idopyr-
                          anosyl-(1 to 3)-beta-D-ribofuranosyl-(1 to
                          5)]-2-deoxy-, sulfate (salt) [USAN 1996]
 SYNONYMS                 Humatin [USAN 1996]
 SYNONYMS                 Amminosidin [AmFAR Tx Dir 1993;6(4)]
 SYNONYMS                 Catenulin [Merck Index 1989]
 SYNONYMS                 Crestomycin [Merck Index 1989]
 SYNONYMS                 Estomycin [Merck Index 1989]
 SYNONYMS                 Hydroxymycin [Merck Index 1989]
 SYNONYMS                 Aminosidine Sulfate [USAN 1996]
 SYNONYMS                 Monomycin A [Merck Index 1989]
 SYNONYMS                 Neomycin E [Merck Index 1989]
 SYNONYMS                 Paucimycin [Merck Index 1989]
 SYNONYMS                 O-2,6-Diamino-2,6-dideoxy-
                          beta-L-idopyranosyl- (1 to
                          3)-O-beta-D-ribofuranosyl-(1 to 5)-O
                          -[2-amino-2-deoxy-alpha-D- glucopyranosyl- (1
                          to 4)]-2-deoxystreptamine sulfate (salt)
                          [USAN 1993]
 SYNONYMS                 Paromomycin I [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 192
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Under aerobic conditions, the
                          aminoglycosides are bactericidal, but their
                          exact mechanism of action is unknown. These
                          antibiotics must be actively transported
                          across the cytoplasmic membrane into
                          susceptible bacteria; two sequential
                          energy-dependent phases, called EDP-I and
                          EDP-II and characterized by slow and very
                          rapid rates of uptake, respectively, have
                          been observed. Based on studies done
                          primarily of streptomycin, the bacterial
                          ribosome is considered to be the principal
                          target of the aminoglycosides. It is still
                          not known why the aminoglycosides are
                          bactericidal, while other antibiotics that
                          impair protein synthesis are usually only
                          bacteriostatic. Bacterial cell death does not
                          appear to correlate with the production of
                          faulty proteins due to misreading of the
                          genetic code. The lethal effect of the
                          aminoglycosides may result from their high
                          affinity for the 30s subunit that leads to
                          essentially irreversible binding, but other
                          mechanisms may be involved. Paromomycin is
                          active against many gram-negative bacilli,
                          principally members of the Enterobacteriaceae
                          (eg, Escherichia coli). Pseudomonas
                          aeruginosa are resistant, however. Many
                          strains of Staphylococcus aureus are
                          susceptible, but most other gram-positive
                          bacteria are resistant. Paromycin is a
                          luminal amebicide. Entamoeba histolytica, the
                          causative organism of amebiasis, Dentamoeba
                          fragilis, and various tapeworms, including
                          Taenia saginata, T. solium, Diphyllobothrium
                          latum, Dipylidium caninum, and Hymenolepis
                          nana, are susceptible to paromomycin.
                          Paromomycin is poorly absorbed in the
                          gastrointestinal tract, and most of a single
                          dose is eliminated in the feces.
                          Nevertheless, to avoid excessive absorption,
                          the drug should be used with caution in
                          patients with renal failure, intestinal
                          inflammation, or ulcerations. [Drug
                          Evaluations Annual 1992] [AHFS Drug
                          Information 1995]
 DISEASES STUDIED/TREATED Currently being investigated for treatment of
                          cryptosporidiosis [AmFAR Tx Dir 1995;7(4)]
                          [NIAID ACTG 192]
 CLASSIFICATION CODE      Antibiotic [AHFS Drug Information 1995]
 CLASSIFICATION CODE      Amebicidal [USAN 1996]
 CLASSIFICATION CODE      Anthelmintic [Drug Evaluations Annual 1992]
 OTHER MAJOR USES         Intestinal amebiasis- acute and chronic;
                          management of hepatic coma- as adjunctive
                          therapy; cestodiasis (tapeworm infections)
                          [AHFS Drug Information 1995]
 SUBSTANCE INTERACTIONS   Penicillins (antipseudomonal penicillins),
                          ethacrynic acid, furosemide, bumentanide,
                          skeletal muscle relaxants, methoxyflurane,
                          amphotericin B, vancomycin, cisplatin,
                          cyclosporine, intravenous indomethacin,
                          cephalothin, and dimenhydrinate all have
                          reported interactions with the
                          aminoglycosides. [Drug Evaluations Annual
                          1992] [Facts and Comparisons 1995]
 ADVERSE EFFECTS          May cause nausea, abdominal cramps, and
                          diarrhea, particularly when doses exceed 3 g
                          daily. Overgrowth of non-susceptible
                          organisms and a malabsorption syndrome may
                          occur after prolonged administration.
                          Possibility of nephrotoxicity in patients
                          with ulcerative lesions. [Drug Evaluations
                          Annual 1992] [AHFS Drug Information 1995]
 CONTRAINDICATIONS        Contraindicated in patients with a history of
                          previous hypersensitivity to the drug. Also
                          contraindicated in those with intestinal
                          obstruction or ulcerative lesions. [AHFS Drug
                          Information 1995] [Drug Evaluations Annual
                          1992]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: An aminoglycoside
                          antibiotic derived from Streptomyces rimosus
                          and structurally related to neomycin,
                          streptomycin and kanamycin [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORM: C23H45N5O14.H2SO4 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 615.65 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C44.87%, H7.37%,
                          N11.38%, O36.38% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water, moderately
                          soluble in methanol, sparingly soluble in abs
                          ethanol [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Amorphous white powder
                          [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Capsules 250 mg. [AHFS Drug
                          Information 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [AHFS Drug
                          Information 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store in tightly closed containers
                          at 15-30 C. [AHFS Drug Information 1995]
 MANUFACTURERS            Parke-Davis / Warner Lambert Company
 REFERENCES               Tan WW, Chapnick EK, Abter EI, Haddad S,
                          Zimbalist EH, Lutwick LI.
                          Paromomycin-associated pancreatitis in
                          HIV-related cryptosporidiosis. Ann
                          Pharmacother. 1995 Jan;29(1):22-4.
 REFERENCES               Mohri H, Fujita H, Asakura Y, Katoh K,
                          Okamoto R, Tanabe J, Harano H, Noguchi T,
                          Inayama Y, Amano T, et al. Case report:
                          inhalation therapy of paromomycin is
                          effective for respiratory infection and
                          hypoxia by cryptosporidium with AIDS. Am J
                          Med Sci. 1995 Jan;309(1):60-2.
 REFERENCES               Scaglia M, Atzori C, Marchetti G, Orso M,
                          Maserati R, Orani A, Novati S, Olliaro P.
                          Effectiveness of aminosidine (paromomycin)
                          sulfate in chronic Cryptosporidium diarrhea
                          in AIDS patients: an open, uncontrolled,
                          prospective clinical trial. J Infect Dis.
                          1994 Nov;170(5):1349-50.
 REFERENCES               Piersimoni C, Bornigia S, De Sio G, Scalise
                          G. Bacteriostatic and bactericidal activities
                          of paromomycin against Mycobacterium avium
                          complex isolates. J Antimicrob Chemother.
                          1994 Sep;34(3):421-4.
 REFERENCES               White AC Jr, Chappell CL, Hayat CS, Kimball
                          KT, Flanigan TP, Goodgame RW. Paromomycin for
                          cryptosporidiosis in AIDS: a prospective,
                          double-blind trial. J Infect Dis. 1994
                          Aug;170(2):419-24.
 REFERENCES               Forester G, Sidhom O, Nahass R, Andavolu R.
                          AIDS-associated cryptosporidiosis with
                          gastric stricture and a therapeutic response
                          to paromomycin. Am J Gastroenterol. 1994
                          Jul;89(7):1096-8.
 REFERENCES               Bissuel F, Cotte L, Rabodonirina M, Rougier
                          P, Piens MA, Trepo C. Paromomycin: an
                          effective treatment for cryptosporidial
                          diarrhea in patients with AIDS. Clin Infect
                          Dis. 1994 Mar;18(3):447-9.
 REFERENCES               Bissuel F, Cotte L, Rabodonirina M, Rougier
                          P, Piens MA, Trepo C. Paromomycin therapy for
                          cryptosporidial diarrhoea in 24 AIDS
                          patients. Int Conf AIDS. 1993 Jun
                          6-11;9(1):56 (abstract no. WS-B13-6).
 REFERENCES               Kanyok TP, Novak RM, Danziger LH. Preliminary
                          results of a randomized, blinded, control
                          study of paromomycin (PRM) vs. placebo (PLC)
                          for the treatment of Cryptosporidium diarrhea
                          (CD) in AIDS patients (P). Int Conf AIDS.
                          1993 Jun 6-11;9(1):386 (abstract no.
                          PO-B10-1508).
 REFERENCES               Walmsley S, Phillips J, Loeb M, Walach C,
                          Salit I, Rachlis A, Fong I. Effectiveness of
                          paromomycin in cryptosporidiosis in AIDS. Int
                          Conf AIDS. 1993 Jun 6-11;9(1):381(abstract
                          no. PO-B10-1473).
 ENTRY MONTH              9309
 LAST REVISION DATE       960417
 

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