Amoxicillin and clavulanate potassium are very well absorbed from the gastrointestinal
tract after oral administration of AUGMENTIN. Dosing within the fasted or fed state
has minimal effect on the pharmacokinetics of amoxicillin. While AUGMENTIN can
receive without regard to meals, absorption of clavulanate potassium when taken
with meals are greater in accordance with the fasted state. In 1 study, the relative
bioavailability of clavulanate was reduced when AUGMENTIN was dosed at 30 and
150 minutes following the oncoming of a high-fat breakfast. The security and efficacy
of AUGMENTIN have been established in clinical trials where AUGMENTIN was taken
without regard to meals.
Meana amoxicillin and clavulanate potassium pharmacokinetic parameters
are shown inside table below:
Doseb and regimen
AUC0-24 (mcg•hr/mL)
Cmax (mcg/mL)
amoxicillin/ clavulanate potassium
amoxicillin (S. D. )
clavulanate potassium (S. D. )
amoxicillin (S. D. )
clavulanate potassium (S. D. )
250/125 mg q8h
26. 7 4. 56
12. 6 3. 25
3. 3 1. 12
1. 5 0. 70
500/125 mg q12h
33. 4 6. 76
8. 6 1. 95
6. 5 1. 41
1. 8 0. 61
500/125 mg q8h
53. 4 8. 87
15. 7 3. 86
7. 2 2. 26
2. 4 0. 83
875/125 mg q12h
53. 5 12. 31
10. 2 3. 04
11. buy phenergan online 6 2. 78
2. 2 0. 99
an average values of 14 normal volunteers
(n = 15 for clavulanate potassium inside low-dose regimens). Peak concentrations
occurred approximately 1. 5 hours as soon as the dose.
b Administered at the start of a lightweight meal.
Amoxicillin serum concentrations achieved with AUGMENTIN act like those
made by the oral administration of equivalent doses of amoxicillin alone. The half-life of amoxicillin following your oral administration of AUGMENTIN is 1. 3
hours and this of clavulanic acid is 1. 0 hour.
Approximately 50% to 70% with the amoxicillin and approximately 25% to 40% of
the clavulanic acid are excreted unchanged in urine through the first 6 hours
after administration of merely one 250-mg or 500-mg tablet of AUGMENTIN.
Concurrent administration of probenecid delays amoxicillin excretion but does
not delay renal excretion of clavulanic acid.
Neither component in AUGMENTIN is very protein-bound; clavulanic acid has
been seen to be approximately 25% sure to human serum and amoxicillin approximately
18% bound.
Amoxicillin diffuses readily into most body tissues and fluids using the exception
from the brain and spinal fluid. The outcome of experiments relating to the administration
of clavulanic acid to animals suggest that this compound, like amoxicillin,
is well distributed in body tissues.
Microbiology
Amoxicillin is really a semisynthetic antibiotic that has a broad spectrum of bactericidal
activity against many gram-positive and gram-negative microorganisms. Amoxicillin
is, however, prone to degradation by β-lactamases, and therefore,
the spectrum of activity doesnt include organisms which produce these enzymes. Clavulanic acid is really a β-lactam, structurally in connection with the penicillins,
which possesses the ability to inactivate numerous β-lactamase enzymes
commonly present in microorganisms resistant to penicillins and cephalosporins. In particular, they have good activity from the clinically important plasmid-mediated
β-lactamases frequently to blame for transferred drug resistance.
The formulation of amoxicillin and clavulanic acid in AUGMENTIN protects amoxicillin
from degradation by β-lactamase enzymes and effectively extends the antibiotic
spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin
along with other β-lactam antibiotics. Thus, AUGMENTIN possesses the properties
of a broad-spectrum antibiotic plus a β-lactamase inhibitor.
Amoxicillin/clavulanic acid may be active against most strains
with the following microorganisms, in both vitro and in clinical infections
as described in INDICATIONS AND USAGE.
Gram-Positive Aerobes
Staphylococcus aureus (β-lactamase and non-β-lactamase-producing)
c Staphylococci that happen to be proof against methicillin/oxacillin must
be regarded immune to amoxicillin/clavulanic acid.
Gram-Negative Aerobes
Enterobacter species (Although most strains of Enterobacter species
are resistant in vitro, clinical efficacy continues to be demonstrated with
AUGMENTIN in bladder infections a result of these organisms. )
Escherichia coli (β-lactamase and non-β-lactamase-producing)
Haemophilus influenzae (β-lactamase and non-β-lactamase-producing)
Klebsiella species (All known strains are β-lactamase-producing. )
Moraxella catarrhalis (β-lactamase and non-β-lactamase-producing)
The following in vitro data can be purchased, but their clinical significance
is unknown.
Amoxicillin/clavulanic acid exhibits in vitro minimal inhibitory concentrations
(MICs) of 2 mcg/mL or less against most ( ≥ 90%) strains of Streptococcus
pneumoniae; MICs of 0. 06 mcg/mL or less against most ( ≥ 90%) strains
of Neisseria gonorrhoeae; MICs of four mcg/mL or less against most ( ≥ 90%)
strains of staphylococci and anaerobic bacteria; and MICs of 8 mcg/mL or less
against most ( ≥ 90%) strains of other listed organisms. However, while using
exception of organisms consideration to answer amoxicillin alone, the security and
effectiveness of amoxicillin/clavulanic acid for treating clinical infections
as a result of these microorganisms were not established in adequate and well-controlled
clinical trials.
Because amoxicillin has greater in vitro activity against S. pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae
strains with intermediate susceptibility to ampicillin or penicillin are fully
prone to amoxicillin.
Gram-Positive Aerobes
Enterococcus faecalise
Staphylococcus epidermidis (β-lactamase and non-β-lactamase-producing)
Staphylococcus saprophyticus (β-lactamase and non-β-lactamase-producing)
Streptococcus pneumoniaee,f
Streptococcus pyogenese,f
viridans group Streptococcuse,f
Gram-Negative Aerobes
Eikenella corrodens (β-lactamase and non-β-lactamase-producing)
Neisseria gonorrhoeaee(β-lactamase and non-β-lactamase-producing)
Proteus mirabilise (β-lactamase and non-β-lactamase-producing)
Anaerobic Bacteria
Bacteroides species, including Bacteroides fragilis (β-lactamase
and non-β-lactamase-producing)
Fusobacterium species (β-lactamase and non-β-lactamase-producing)
Peptostreptococcus species¶
eAdequate and well-controlled numerous studies have established the
effectiveness of amoxicillin alone for certain clinical infections due
to organisms.
f They are non-β-lactamase-producing organisms, and thus,
are given to amoxicillin alone.
Susceptibility Testing
Dilution Techniques: Quantitative methods are
familiar with determine antimicrobial MICs. These MICs provide estimates with the susceptibility
of bacteria to antimicrobial compounds. The MICs should be determined using
a standardized procedure. Standardized procedures are based on a dilution method1
(broth or agar) or equivalent with standardized inoculum concentrations and
standardized concentrations of amoxicillin/clavulanate potassium powder.
The recommended dilution pattern works with a constant amoxicillin/clavulanate
potassium ratio of 2 to a single to all tubes with varying degrees of amoxicillin. MICs are expressed with regards to the amoxicillin concentration from the presence
of clavulanic acid with a constant 2 parts amoxicillin one part clavulanic acid. The MIC values really should be interpreted based on the following criteria:
Inerpretive Criteria For Amoxicillin/Clavulanic Acid Susceptibility Testing
For Gram-Negative Enteric Aerobes
MIC (mcg/mL)
Interpretation
≤ 8/4
Susceptible(S)
16/8
Intermediate(I)
≥ 32/16
Resistant(R)
For Staphylococcus aureusg and Haemophilus influenzae
MIC (mcg/mL)
Interpretation
≤ 4/2
Susceptible (S)
≥ 8/4
Resistant (R)
g Staphylococci which might be vunerable to amoxicillin/clavulanic
acid but resistance against methicillin/oxacillin has to be regarded as resistant.
For S. pneumoniae from non-meningitis sources: Isolates should
be tested using amoxicillin/clavulanic acid along with the following criteria should
provide:
MIC (mcg/mL)
Interpretation
≤ 4/2
Susceptible (S)
≥ 8/4
Resistant (R)
NOTE: These interpretive criteria use the recommended doses
for respiratory tract infections.
A report of "Susceptible" indicates that the pathogen is liable
for being inhibited if your antimicrobial compound inside the blood reaches the concentration
usually achievable. A written report of "Intermediate" suggests that the
result might be of interest equivocal, and, in the event the microorganism will not be fully
prone to alternative, clinically feasible drugs, test should be repeated. This category implies possible clinical applicability in body sites the spot that the
drug is physiologically concentrated or even in situations where high dosage of drug
can be utilized. This category also provides a buffer zone, which prevents small
uncontrolled technical factors from causing major discrepancies in interpretation. Research of "Resistant" signifies that the pathogen is not likely
to be inhibited if the antimicrobial compound from the blood reaches the concentrations
usually achievable; other therapy should be selected.
Standardized susceptibility test procedures have to have the by using laboratory control
microorganisms to manipulate the technical issues with the laboratory procedures. Standard amoxicillin/clavulanate potassium powder ought to provide this
MIC values:
Microorganism
MIC Range (mcg/mL)h
Escherichia coli ATCC 25922
2 to eight
Escherichia coli ATCC 35218
4 to 16
Haemophilus influenzae ATCC 49247
2 to 16
Staphylococcus aureus ATCC 29213
0. 12 to 0. 5
Streptococcus pneumoniae ATCC 49619
0. 03 to 0. 12
h Expressed as concentration of
amoxicillin inside presence of clavulanic acid in a constant 2 parts amoxicillin
to a single part clavulanic acid.
Diffusion Techniques: Quantitative methods that require measurement
of zone diameters offer reproducible estimates in the susceptibility
of bacteria to antimicrobial compounds. The type of standardized procedure2
necessitates the utilization of standardized inoculum concentrations. This process uses
paper disks impregnated with 30 mcg of amoxicillin/clavulanate potassium (20
mcg amoxicillin plus 10 mcg clavulanate potassium) to test the susceptibility
of microorganisms to amoxicillin/clavulanic acid.
Reports from your laboratory providing results of the typical single-disk susceptibility
test which has a 30-mcg amoxicillin/clavulanate acid (20 mcg amoxicillin plus 10
mcg clavulanate potassium) disk needs to be interpreted good following
criteria:
Interpretive Criteria For Amoxicillin/Clavulanic Acid Susceptibility Testing
For Gram-Negative Enteric Aerobes
Zone Diameter (mm)
Interpretation
≥ 18
Susceptible(S)
14 to 17
Intermediate(I)
≤ 13
Resistant(R)
For Staphylococcus aureusi and Haemophilus influenzaej
Zone Diameter (mm)
Interpretation
≥ 20
Susceptible (S)
≤ 19
Resistant (R)
i Staphylococci which might be proof against methicillin/oxacillin must
be regarded as as immune to amoxicillin/clavulanic acid.
j A broth microdilution method really should be used in testing Haemophilus
influenzae.
Beta-lactamase-negative, ampicillin-resistant strains has to be considered resistant
to amoxicillin/clavulanic acid.
Interpretation needs to be mentionened above previously above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test
while using MIC for amoxicillin/clavulanic acid.
As with standardized dilution techniques, diffusion methods have to have the use
of laboratory control microorganisms which might be familiar with control the technical
facets of the laboratory procedures. For that diffusion technique, the 30-mcg
amoxicillin/clavulanate potassium (20-mcg amoxicillin plus 10-mcg clavulanate
potassium) disk should provide this zone diameters within these laboratory
qc strains:
Microorganism
Zone Diameter (mm)
Escherichia coli ATCC 25922
18 to 24
Escherichia coli ATCC 35218
17 to 22
Staphylococcus aureus ATCC 25923
28 to 36
Haemophilus influenza ATCC 49247
15 to 23
Scientific tests
Data from 2 pivotal studies in 1,191 patients treated for either lower respiratory
tract infections or complicated utis compared a regimen
of 875-mg tablets of AUGMENTIN q12h to 500-mg tablets of AUGMENTIN dosed q8h
(584 and 607 patients, respectively). Comparable efficacy was demonstrated between
the q12h and q8h dosing regimens. There seemed to be no significant difference inside the
amount of adverse events in each group. The most frequently reported adverse
event was diarrhea; incidence rates were similar to the 875-mg q12h and 500-mg
q8h dosing regimens (14. 9% and 14. 3%, respectively); however, there was clearly a statistically
factor (p < 0. 05) in rates of severe diarrhea or withdrawals
with diarrhea between the regimens: 1. 0% for 875-mg q12h dosing versus 2. 5%
for the 500-mg q8h dosing.
In 1 these pivotal studies, 629 patients with either pyelonephritis or even a
complicated bladder infection (i. e. , patients with abnormalities on the
urinary tract that predispose to relapse of bacteriuria following eradication)
were randomized to obtain either 875-mg tablets of AUGMENTIN q12h or 500-mg
tablets of AUGMENTIN q8h inside the following distribution:
875 mg q12h
500 mg q8h
Pyelonephritis
173 patients
188 patients
Complicated UTI
135 patients
133 patients
Total patients
308
321
The amount of bacteriologically evaluable patients was comparable relating to the
2 dosing regimens. AUGMENTIN produced comparable bacteriological success rates
in patients assessed 3 to 5 days right after end of therapy. The bacteriologic
efficacy rates were comparable at This is the follow-up visits (5 to 9 days post-therapy)
and at a late post-therapy visit (in the tastes cases, this is Three to five
weeks post-therapy), as observed in the table below:
875 mg q12h
500 mg q8h
Three to five days
81%, n = 58
80%, n = 54
5 to 9 days
58. 5%, n = 41
51. 9%, n = 52
2 to 4 weeks
52. 5%, n = 101
54. 8%, n = 104
As noted before, though there is no significant difference in the percentage
of adverse events in each group, there was a statistically significant difference
in rates of severe diarrhea or withdrawals with diarrhea involving the regimens.
REFERENCES
1. Clinical and Laboratory Standards Institute (CLSI). Methods
for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically;
Approved Standard - 8th ed. CLSI Document M07-A8. CLSI, 940 West Valley Rd. ,
Suite 1400, Wayne, PA 19087, 2009.
2. Clinical and Laboratory Standards Institute (CLSI). Performance
Standards for Antimicrobial Disk Susceptibility Test; Approved Standard - 10th
ed. CLSI Document M02-A10. CLSI, 940 West Valley Rd. , Suite 1400, Wayne, PA
19087, 2009.
Last reviewed on RxList: 10/13/2011
This monograph is modified to feature the generic and name brand in many instances.
