      Document 0148
 DOCN  DRG0148
 UNIQUE IDENTIFIER        DRG-0099
 NAME OF SUBSTANCE        Clarithromycin [USAN 1996]
 REGISTRY NUMBER          81103-11-9
 STANDARD CHEMICAL NAME   6-0-Methylerythromycin [PDR 1995]
 SYNONYMS                 A-56268 [USAN 1996]
 SYNONYMS                 Clathromycin [Merck 1989]
 SYNONYMS                 TE-031 [USAN 1996]
 SYNONYMS                 6-O-methylerythromycin [USAN 1996]
 SYNONYMS                 Biaxin [USAN 1996]
 PROTOCOL ID NUMBERS      NIAID ACTG 157
 PROTOCOL ID NUMBERS      NIAID 90 CC-04
 PROTOCOL ID NUMBERS      NCI 91 C-53
 PROTOCOL ID NUMBERS      NIAID DATRI 001
 PROTOCOL ID NUMBERS      FDA 048D
 PROTOCOL ID NUMBERS      FDA 214A
 PROTOCOL ID NUMBERS      FDA 226B
 PROTOCOL ID NUMBERS      NIAID ACTG 223
 PROTOCOL ID NUMBERS      NIAID ACTG 237
 PROTOCOL ID NUMBERS      NIAID CPCRA 027
 PROTOCOL ID NUMBERS      NIAID DATRI 007
 PROTOCOL ID NUMBERS      FDA 124A
 PROTOCOL ID NUMBERS      NIAID ACTG 178
 PROTOCOL ID NUMBERS      NIAID ACTG 196
 PROTOCOL ID NUMBERS      NIAID 95 CC-102
 PROTOCOL ID NUMBERS      NIAID ACTG 283
 IND NUMBER               31703
 SECONDARY SOURCE ID      Abbott Protocol M90-494 [NIAID 90-CC-04]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Clarithromycin, is a
                          14-membered macrolide which demonstrates a
                          broad in vitro antibacterial spectrum which
                          includes staphylococci, streptococci,
                          Legionella, Haemophilus influenzae, Neisseria
                          gonorrhoeae, Chlamydia and anaerobes.  A
                          derivative of erythromycin, it inhibits
                          protein synthesis in susceptible organisms by
                          binding to 50S ribosomal subunits, thereby
                          inhibiting translocation of aminoacyl
                          transfer-RNA and inhibiting polypeptide
                          synthesis. Clarithromycin differs from
                          erythromycin by the substitution of a methoxy
                          for a hydroxy group at position 6 of the
                          macrolide ring and its metabolite, unlike
                          that of erythromycin has been shown to be
                          microbiologically active. Clarithromycin has
                          better bacteriologic activity than
                          erythromycin and the presence of the methyl
                          group at the 6-position confers greater acid
                          stability to the erythronolide ring thereby
                          preventing formation of the inactive
                          6,9-9,12-spiroketal derivative.
                          Clarithromycin is well absorbed orally and
                          has a longer half-life in serum than
                          erythromycin does. Since clarithromycin is
                          more lipophilic, it may be able to penetrate
                          the lipid coat of some bacteria more readily
                          than erythromycin can. Clarithromycin has
                          been reported to achieve high concentrations
                          in tissue and to have high intracellular
                          concentrations. Since clarithromycin is more
                          acid stable than erythromycin, it is possible
                          that it would remain active for a longer
                          period of time than erythromycin in the
                          acidic environment of the phagolysosome.
                          [AHFS Drug Information 1995] [Antimicrobial
                          Agents and Chemotherapy Sept 1989, 33(9)]
                          [Drug Metabolism and Disposition 1990, 18(4)]
 DISEASES STUDIED/TREATED FDA approved 12/23/93 (Biaxin) as a treatment
                          for disseminated Mycobacterium avium Complex
                          (MAC) [Am FAR Tx Dir 1993;6(3)]
 DISEASES STUDIED/TREATED FDA approved 10/12/95 for the prevention of
                          disseminated Mycobacterium avium Complex
                          (MAC) in patients with advanced HIV infection
                          [Abbott Laboratories Package Insert 10/95]
 DISEASES STUDIED/TREATED Under investigation in combination therapy
                          for toxoplasmosis [AmFAR Tx Dir 1993;6(3)]
                          [AHFS Drug Information 1995]
 CLASSIFICATION CODE      Antibacterial [USAN 1996]
 OTHER MAJOR USES         Treatment of common bacterial infections of
                          the upper and lower respiratory tract, and
                          the skin [PDR 1995]
 SUBSTANCE INTERACTIONS   Interacts with theophylline, carbamazepine,
                          digoxin, anticoagulants, ergotamine,
                          triazolam, cyclosporine, hexobarbital,
                          phenytoin, warfarin, anti-infective agents,
                          and drugs metabolized by the cytochrome P450
                          system (may cause serum levels of these drugs
                          to elevate). Clarithromycin increases
                          terfenadine plasma levels 3-fold and
                          decreases zidovudine steady state levels.
                          [PDR 1995]
 ADVERSE EFFECTS          The most frequently reported side effects,
                          whether drug related or not, were diarrhea,
                          nausea, abnormal taste, dyspepsia, abdominal
                          pain/discomfort and headache. At high doses
                          (greater than 2000 mg bid) clarithromycin can
                          cause severe abdominal pain. [PDR 1995]
                          [AmFAR Tx Dir 1993;6(3)]
 CONTRAINDICATIONS        Contraindicated in patients with known
                          hypersensitivity to clarithromycin,
                          erythromycin, or any of the macrolide
                          antibiotics, should not be used in pregnancy,
                          and with caution in those with renal or
                          hepatic dysfunction. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Semisynthetic macrolide
                          antibiotic [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C38H69NO13 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 747.96 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C61.02%, H9.30%,
                          N1.87%, O27.81% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 217-220 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: UV max (CHCl3): 288 nm;
                          stable at acidic pH [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Colorless needles from
                          chloroform + diisopropyl ether [1:2]; also
                          reported as crystals from ethanol [Merck
                          Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in acetone, slightly
                          soluble in methanol, ethanol and
                          acetonitrile, and practically insoluble in
                          water [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets (250 AND 500 mg), oral
                          suspension (125 and 250 mg/5ml). [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Should be stored in tight containers
                          at a temperature less than 40 C, preferably
                          between 15-30 C. Do not refrigerate oral
                          suspension. Protect from light [PDR 1995]
 MANUFACTURERS            Abbott
 REFERENCES               Dautzenberg B, Piperno D, Diot P,
                          Truffot-Pernot C, Chauvin JP. Clarithromycin
                          in the treatment of Mycobacterium avium lung
                          infections in patients without AIDS. Chest.
                          1995 Apr;107(4):1035-40.
 REFERENCES               Chaisson RE, Benson CA, Dube MP, Heifets LB,
                          Korvick JA, Elkin S, Smith T, Craft JC,
                          Sattler FR. Clarithromycin therapy for
                          bacteremic Mycobacterium avium complex
                          disease. A randomized, double-blind,
                          dose-ranging study in patients with AIDS. Ann
                          Intern Med. 1994 Dec 15;121(12):905-11.
 REFERENCES               Husson RN, Ross LA, Sandelli S, Inderlied CB,
                          Venzon D, Lewis LL, Woods L, Conville PS,
                          Witebsky FG, Pizzo PA. Orally administered
                          clarithromycin for the treatment of systemic
                          Mycobacterium avium complex infection in
                          children with acquired immunodeficiency
                          syndrome. J Pediatr. 1994 May;124(5 Pt
                          1):807-14.
 REFERENCES               Wallace RJ Jr, Brown BA, Griffith DE, Girard
                          WM, Murphy DT, Onyi GO, Steingrube VA,
                          Mazurek GH. Initial clarithromycin
                          monotherapy for Mycobacterium
                          avium-intracellulare complex lung disease. Am
                          J Respir Crit Care Med. 1994
                          May;149(5):1335-41.
 REFERENCES               Pierce M, Heifets L, Crampton S.
                          Clarithromycin for the prevention of M. avium
                          complex in AIDS. Int Conf AIDS. 1994 Aug
                          7-12;10(2):70 (abstract no. 558B).
 REFERENCES               Vance E, Guzman J, Bitar M, Kazanjian P.
                          Clarithromycin and zidovudine pharmacokinetic
                          study. Int Conf AIDS. 1994 Aug 7-12;10(2):201
                          (abstract no. PB0816).
 REFERENCES               Oualls J, Salvato P, Thompson C. MAIC
                          prevention: clarithromycin vs. rifabutin. Int
                          Conf AIDS. 1994 Aug 7-12;10(2):178 (abstract
                          no. PB0726).
 REFERENCES               McIntyre K, Torres R, Barr M, George N, Shay
                          W. Open study of clarithromycin for primary
                          prevention of symptomatic Mycobacterium avium
                          complex (MAC) disease. Int Conf AIDS. 1993
                          Jun 6-11;9(1)333 (abstract no. PO-B07-1185).
 REFERENCES               Barradell LB, Plosker GL, McTavish D.
                          Clarithromycin. A review of its
                          pharmacological properties and therapeutic
                          use in Mycobacterium avium-intraceellulare
                          complex infection in patients with acquired
                          immune deficiency syndrome. Drugs. 1993
                          Aug;46(2):289-312.
 REFERENCES               Dautzenberg B, Saint Marc T, Meyohas MC,
                          Eliaszewitch M, Haniez F, Rogues AM, De Wit
                          S, Cotte L, Chauvin JP, Grosset J.
                          Clarithromycin and other antimicrobial agents
                          in the treatment of disseminated
                          Mycobacterium avium infections in patients
                          with acquired immunodeficiency syndrome. Arch
                          Intern Med. 1993 Feb 8;153(3):368-72.
 ENTRY MONTH              9101
 LAST REVISION DATE       960501
 

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