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Klacid
PRODUCT NAME
Clarithromycin Tablets
DESCRIPTION
Clarithromycin is a semi-synthetic macrolide antibiotic obtained by
substitution of the hydroxyl group in position 6 by a CH30 group in the
erythromycin lactonic ring. Specifically clarithromycin is 6-0-Methyl
Erythromycin A. The white to off-white antibiotic powder is bitter,
practically odorless, essentially insoluble in water, and slightly soluble
in ethanol, methanol, and acetonitrile. Its molecular weight is 747.96 and
the structural formula is as follows:
Clarithromycin is available in
Filmtab tablets, containing 500 mg of the active antibiotic. The tablets may
also contain a number of inactive ingredients such as dyes, coatings,
lubricants, fillers, etc.
PHARMACEUTICAL FORM
A yellow, ovaloid film-coated tablet containing 500mg of Clarithromycin.
CLINICAL PHARMACOLOGY
Microbiology
Clarithromycin exerts its antibacterial action by binding to the 5OS
ribosomal subunits of susceptible bacteria and suppressing protein
synthesis.
Clarithromycin has demonstrated excellent in vitro activity against both
standard strains of bacteria and clinical isolates. It is highly potent
against a wide variety of aerobic and anaerobic Gram-positive and
Gram-negative organisms. The minimum inhibitory concentrations (MIC's) of clarithromycin are generally one log2 dilution more potent than the MIC's of
erythromycin.
In vitro data also indicate clarithromycin has excellent activity against
Legionella pneumophila, and Mycoplasma pneumoniae. It is bactericidal to
Helicobacter pylori; this activity of clarithromycin is greater at neutral pH
than at acid pH. In vitro and in vivo data show this antibiotic has activity
against clinically significant mycobacterial species. The in vitro data
indicate Enterobacteriaceae, pseudomonas species and other non-lactose
fermenting gram negative bacilli are not sensitive to clarithromycin.
Clarithromycin has been shown to be active against most strains of the
following microorganisms both in vitro and in clinical infections as
described in the Indications and Usage section:
Aerobic Gram-Positive microorganisms
Staphylococcus aureus
Streptococcus pneumoniae
Streptococcus pyogenes
Listeria monocytogenes
Aerobic Gram-negative microorganisms
Haemophilus influenzae
Haemophilus
parainfluenzae
Moraxella catarrhalis
Neisseria gonorrhoeae
Legionella
pneumophila
Other microorganisms
Mycoplasma pneumoniae
Chlamydia pneumoniae (TWAR)
Mycobacteria
Mycobacterium leprae
Mycobacterium kansasii
Mycobacterium chelonae
Mycobacterium fortuitum
Mycobacterium avium complex (MAC) consisting of: Mycobacterium avium,
Mycobacterium Intracellulare
Beta-lactamase production should have no effect on clarithromycin activity.
NOTE: Most strains of methicillin-resistant and oxacillin-resistant
staphylococci are resistant to
clarithromycin.
Helicobacter
Helicobacter pylori
In cultures performed prior to therapy, H. pylon was isolated and
clarithromycin MIC's were determined pre-treatment in 104 patients. Of
these, four patients had resistant strains, two patients had strains with
intermediate susceptibility, and 98 patients had susceptible strains.
The following in vitro data are available, but their clinical significance
is unknown. Clarithromycin exhibits in vitro activity against most strains
of the following microorganisms; however, the safety and effectiveness of clarithromycin in treating clinical infections due to these microorganisms
have not been established in adequate and well-controlled clinical trials.
Aerobic Gram-positive microorganisms
Streptococcus agalactiae
Streptococci
(Group C,F,G)
Viridans group streptococci
Aerobic Gram-negative microorganisms
Bordetella pertussis
Pasteurella multocida
Anaerobic Gram-positive microorganisms
Clostridium perfringens
Peptococcus
niger
Propionibactenum acnes
Anaerobic Gram-negative microorganisms
Bacteroides melaninogenicus
Spirochetes
Borrelia burgdorferi
Treponema pallidum
Campylobacter
Campylobacter jejuni
The principal metabolite of clarithromycin in man and other primates is a
microbiologicallyactive metabolite, 14-OH-clarithromycin. This metabolite is
as active or 1- to 2-fold less active than the parent compound for most
organisms, except for H. influenzae against which it is twice as active. The
parent compound and the 14-OH metabolite exert either an additive or
synergistic effect on H. influenzae in vitro and in vivo, depending on
bacterial strains.
Clarithromycin was found to be two to ten times more active than
erythromycin in several experimental animal infection models. It was shown,
for example, to be more effective than erythromycin in mouse systemic
infection, mouse subcutaneous abscess, and mouse respiratory tract
infections caused by S. pneumoniae, S. aureus, S. pyogenes, and
H. influenzae. In guinea pigs with Legionella infection this effect was more
pronounced; an intraperitoneal dose of 1.6 mg/kg/day of clarithromycin was
more effective than 50 mg/kg/day of erythromycin.
Susceptibility Tests
Quantitative methods that require measurement of zone diameters give the
most precise estimates of susceptibility of bacteria to antimicrobial
agents. One recommended procedure uses discs impregnated with 15 mcg of
clarithromycin for testing susceptibility (Kirby-Bauer diffusion test);
interpretations correlate inhibition zone diameters of this disc test with
MIC values for clarithromycin. The MIC's are determined by the broth or agar
dilution method.
With these precedes, a report from the laboratory of "susceptible" indicates
the infecting organism is likely to respond to therapy. A report of
"resistant" indicates the infective organism is not likely to respond to
therapy A report of "Intermediate Susceptibility" suggests the therapeutic
effect of the drug may be equivocal or the organism would be susceptible if
higher doses were used. (Intermediate susceptibility is also referred to as
moderately susceptible.)
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