Mechanism Of Action
Amoxicillin is an antibacterial
drug. [see Microbiology]
MOXATAG is an extended-release
formulation of amoxicillin intended to provide once-daily dosing. Following the
administration of MOXATAG with a low-fat meal in healthy subjects, mean
amoxicillin AUC0-∞, Cmax, and Tmax values were 29.8 μg•h/mL, 6.6
μg/mL and 3.1 hours, respectively. The mean plasma concentration-time
curve is shown below in Figure 1.
Figure 1: Mean Amoxicillin Plasma Concentrations
Following a Single Oral Dose of MOXATAG With a Low-Fat Meal in Healthy Subjects
Administration of MOXATAG with food decreases the rate,
but not the extent of amoxicillin absorption. Compared to immediate-release
amoxicillin suspension, the rate of amoxicillin absorption following
administration of MOXATAG was slower, resulting in a lower Cmax and longer
Tmax. Total amoxicillin exposure (AUC) achieved with MOXATAG is similar to that
observed after oral administration of a comparable dose of immediate-release
Amoxicillin diffuses readily into most body tissues and
fluids, with the exception of brain and spinal fluid, except when meninges are
inflamed. Amoxicillin is approximately 20% protein bound in human serum.
Amoxicillin is primarily
cleared by renal excretion. Approximately 60% of an oral dose of
immediate-release amoxicillin is eliminated unchanged in urine. The half-life
of amoxicillin after oral administration of MOXATAG is approximately 1.5 hours,
similar to that of immediate-release amoxicillin. No accumulation of
amoxicillin was observed after once-daily dosing of 775 mg of MOXATAG for 7
In a study of healthy adult
subjects, amoxicillin AUC was similar whereas Cmax increased approximately 35%
following the administration of lansoprazole with MOXATAG given with food.
Probenecid decreases the renal
tubular secretion of amoxicillin. Concurrent use of MOXATAG and probenecid may
result in increased and prolonged blood levels of amoxicillin. The clinical
relevance of this finding has not been evaluated.
Mechanism of Action
Amoxicillin is similar to
penicillin in its bacterial action against susceptible organisms during the
stage of active multiplication. It acts through the inhibition of cell wall
biosynthesis that leads to the death of the bacteria.
Mechanism of Resistance
To date there are no known
mechanisms of resistance to penicillin or amoxicillin in Streptococcus
Amoxicillin has been shown to
be active in vitro against isolates of the microorganism S. pyogenes and
in clinical infections as described in the INDICATIONS AND USAGE section.
The following in vitro data are
available, but their clinical significance is unknown. At least 90% of the
following microorganisms exhibit an in vitro minimum inhibitory concentration
(MIC) less than or equal to the susceptibility breakpoint of amoxicillin (as
determined by susceptibility tests using the class representative agents
penicillin or ampicillin).
Streptococcus spp. (Group B, C, and G;
Susceptibility Test Methods
When available, the clinical
microbiology laboratory should provide cumulative in vitro susceptibility test
results for antimicrobial drugs used in local hospitals and practice areas to the
physician as periodic reports that describe the susceptibility profile of
nosocomial and community-acquired pathogens. These reports should aid the
physician in selecting the most effective antimicrobial.
Quantitative methods are used
to determine antimicrobial MICs. These MICs provide estimates of the
susceptibility of bacteria to antimicrobial compounds. The MICs should be
determined using a standardized method (broth or agar)1,2.
beta-hemolytic streptococcal isolates to amoxicillin may be inferred by testing
penicillin. An organism that is susceptible to penicillin can be considered
susceptible to amoxicillin when used for approved indications2. If
testing is performed, any beta hemolytic streptococcal isolate found to be
nonsusceptible should be reidentified, retested, and if confirmed, submitted to
a public health laboratory.
test procedures1,2 require the use of laboratory controls to monitor
and ensure the accuracy and precision of the supplies and reagents used in the
assay, and the techniques of the individuals performing the test. Standard
amoxicillin powder should provide the following range of MIC values provided in
Table 2: Acceptable Quality
Control Ranges for Amoxicillina
|Quality Control Organism
||Minimum Inhibitory Concentrations (mcg/mL)
||Disk Diffusion Zone Diameters (mm)
|Streptococcus pneumoniae ATCCb 49619
|Klebsiella pneumoniae ATCC 700603
|| > 128
|aQC limits for testing E. coli 35218 when tested on
Haemophilus Test Medium (HTM) are greater than 256 mcg/mL for amoxicillin;
testing amoxicillin may help to determine if the isolate has maintained its
ability to produce beta-lactamase2.
bATCC = American Type Culture Collection
In a randomized,
parallel-group, multi-center, double-blind, double-dummy study in adults and
pediatrics (age ≥ 12 years) with tonsillitis and/or pharyngitis secondary
to S. pyogenes, MOXATAG 775 mg QD for 10 days was non-inferior to penicillin VK
250 mg QID for 10 days.
Using strict evaluability and microbiologic
response criteria 4-8 days post-therapy, the following bacteriological
eradication rates and statistical outcomes in the per-protocol (PPb) and
modified intent-to-treat (mITT) populations were obtained (Table 3). The mITT
population included all randomized patients with a positive throat culture for S.
pyogenes at baseline. The PPb population included mITT patients who had
post-therapy cultures, were compliant with treatment, and didn't have major
Table 3: Bacteriological
Eradication Rates in Patients with Tonsillitis and/or Pharyngitis
||Rate Difference 95% CI (%)
||1.6 (-5.1, 8.2)
||1.7 (-5.4, 8.7)
1. Clinical and Laboratory Standards Institute (CLSI). Methods
for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow
Aerobically; Approved Standard – Tenth Edition. CLSI document M07-A10, Clinical
and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne,
Pennsylvania 19087, USA, 2015.
2. Clinical and Laboratory Standards Institute (CLSI). Performance
Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational
Supplement, CLSI document M100-S25, Clinical and Laboratory Standards
Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA,