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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 suspension.
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 days.
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 pyogenes.
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; Beta-hemolytic)
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.
Susceptibility of 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.
Standardized susceptibility 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 22.
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||0.03-0.12||---|
|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 protocol violations.
Table 3: Bacteriological
Eradication Rates in Patients with Tonsillitis and/or Pharyngitis
|Study Population||MOXATAG||Penicillin VK||Rate Difference 95% CI (%)|
|PPb||198/233 (85.0%)||191/229 (83.4%)||1.6 (-5.1, 8.2)|
|mITT||204/256 (79.7%)||206/264 (78.0%)||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, 2015.
Last reviewed on RxList: 7/1/2015
This monograph has been modified to include the generic and brand name in many instances.
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