To reduce the development of drug-resistant bacteria and maintain the
effectiveness of amoxicillin and other antibacterial drugs, amoxicillin should
be used only to treat or prevent infections that are proven or strongly
suspected to be caused by bacteria.
Description
Formulations of amoxicillin tablets, USP contain
amoxicillin, a semisynthetic antibiotic, an analog of ampicillin, with a broad
spectrum of bactericidal activity against many gram-positive and gram-negative
microorganisms. Chemically, it is
(2S,5R,6R)-6-[(R)-(-)-2-amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic
acid trihydrate. It may be represented structural formula as: The amoxicillin molecular formula is C16H19N3O5S•3H2O, and the molecular weight is 419.45. Tablets of
amoxicillin are intended for oral administration.
Each film coated tablet
contains 875 mg amoxicillin as the trihydrate. The 875 mg Pink colored, capsule
shaped, film coated tablets debossed with “A” on one side and with a score line
in between “6” and “7” on the other side. Inactive ingredients: Colloidal
silicon dioxide, crospovidone, D and C Red No. 30 aluminum lake, hypromellose,
magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium
starch glycolate, and titanium dioxide.
Clinical Pharmacology
Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed
after oral administration. The effect of food on the absorption of amoxicillin
from the tablets and suspension of amoxicillin has been partially investigated.
The 400 mg and 875 mg formulations have been studied only when administered at
the start of a light meal. However, food effect studies have not been performed
with the 200 mg and 500 mg formulations. Amoxicillin diffuses readily into most
body tissues and fluids, with the exception of brain and spinal fluid, except
when meninges are inflamed. The half-life of amoxicillin is 61.3 minutes. Most
of the amoxicillin is excreted unchanged in the urine; its excretion can be
delayed by concurrent administration of probenecid. In blood serum, amoxicillin
is approximately 20% protein-bound. Orally administered doses of 250 mg
and 500 mg amoxicillin capsules result in average peak blood levels 1 to 2 hours
after administration in the range of 3.5 mcg/mL to 5 mcg/mL and 5.5 mcg/mL to
7.5 mcg/mL, respectively. Mean amoxicillin pharmacokinetic parameters
from an open, two-part, single-dose crossover bioequivalence study in 27 adults
comparing 875 mg of amoxicillin with 875 mg of amoxicillin/clavulanate potassium
showed that the 875 mg tablet of amoxicillin produces an AUC0-∞ of 35.4 ± 8.1 mcg•hr/mL and a Cmax
of 13.8 ± 4.1 mcg/mL. Dosing was at the start of a light meal following an
overnight fast. Orally administered doses of amoxicillin suspension, 125
mg/5 mL and 250 mg/5 mL, result in average peak blood levels 1 to 2 hours after
administration in the range of 1.5 mcg/mL to 3 mcg/mL and 3.5 mcg/mL to 5
mcg/mL, respectively. Oral administration of single doses of 400 mg
chewable tablets and 400 mg/5 mL suspension of amoxicillin to 24 adult
volunteers yielded comparable pharmacokinetic data:
Dose *
AUC 0-∞ (mcg•hr/mL)
Cmax (mcg/mL)†
Amoxicillin
Amoxicillin
Amoxicillin
(±S.D.)
(±S.D.)
400 mg (5 mL of suspension)
17.1 (3.1)
5.92 (1.62)
400 mg (1 chewable tablet)
17.9 (2.4)
5.18 (1.64)
* Administered at the start of a light meal.† Mean values of 24 normal volunteers. Peak concentrations occurred approximately 1 hour after the dose.
Detectable serum levels are observed up to 8 hours after an orally administered
dose of amoxicillin. Following a 1 gram dose and utilizing a special skin window
technique to determine levels of the antibiotic, it was noted that therapeutic
levels were found in the interstitial fluid. Approximately 60% of an orally
administered dose of amoxicillin is excreted in the urine within 6 to 8 hours.
Microbiology
Amoxicillin is similar to ampicillin in its bactericidal action against
susceptible organisms during the stage of active multiplication. It acts through
the inhibition of biosynthesis of cell wall mucopeptide. Amoxicillin 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
Enterococcus faecalis
Staphylococcus spp.* (β-lactamase–negative strains
only)
Streptococcus pneumoniae
Streptococcus spp. (α- and β-hemolytic strains
only) *Staphylococci which are susceptible to amoxicillin but resistant
to methicillin/oxacillin should be considered as resistant to
amoxicillin.
Aerobic Gram-Negative Microorganisms
Escherichia coli (β-lactamase–negative strains
only)
Haemophilus influenzae (β-lactamase–negative
strains only)
Neisseria gonorrhoeae
(β-lactamase–negative strains only)
Proteus
mirabilis (β-lactamase–negative strains only)
Helicobacter
Helicobacter pylori
Susceptibility
Tests
Dilution Techniques
Quantitative
methods are used to determine antimicrobial minimum inhibitory concentrations
(MICs). These MICs provide estimates of 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 ampicillin powder. Ampicillin is sometimes used to predict
susceptibility of S. pneumoniae to amoxicillin;
however, some intermediate strains have been shown to be susceptible to
amoxicillin. Therefore, S. pneumoniae susceptibility
should be tested using amoxicillin powder. The MIC values should be interpreted
according to the following criteria:
For Gram-Positive Aerobes
Enterococcus
MIC
(mcg/mL)
Interpretation
≤8
Susceptible (S)
≥16
Resistant (R)
Staphylococcus
a
MIC
(mcg/mL)
Interpretation
≤0.25
Susceptible (S)
≥0.5
Resistant (R)
Streptococcus (except S.
pneumoniae)
MIC
(mcg/mL)
Interpretation
≤0.25
Susceptible (S)
0.5 to 4
Intermediate (I)
≥8
Resistant (R)
S. pneumoniae
b from non-meningitis
sources.(Amoxicillin powder should be used to
determine susceptibility.)
MIC
(mcg/mL)
Interpretation
≤2
Susceptible (S)
4
Intermediate (I)
≥8
Resistant (R)
NOTE: These interpretive criteria are based on the recommended
doses for respiratory tract infections.
For Gram-Negative Aerobes
Enterobacteriaceae
MIC
(mcg/mL)
Interpretation
≤8
Susceptible (S)
16
Intermediate (I)
≥32
Resistant (R)
H. influenzae
c
MIC
(mcg/mL)
Interpretation
≤1
Susceptible (S)
2
Intermediate (I)
≥4
Resistant (R)
a.
Staphylococci which are susceptible to amoxicillin but resistant to
methicillin/oxacillin should be considered as resistant to amoxicillin.b.
These interpretive standards are applicable only to broth microdilution
susceptibility tests using cation-adjusted Mueller-Hinton broth with 2 to 5%
lysed horse blood.c. These interpretive standards are applicable only to
broth microdilution test with H. influenzae using
Haemophilus Test Medium (HTM).1
A report of “Susceptible” indicates that the pathogen
is likely to be inhibited if the antimicrobial compound in the blood reaches the
concentrations usually achievable. A report of “Intermediate” indicates that the
result should be considered equivocal, and, if the microorganism is not fully
susceptible to alternative, clinically feasible drugs, the test should be
repeated. This category implies possible clinical applicability in body sites
where the drug is physiologically concentrated or in situations where high
dosage of drug can be used. This category also provides a buffer zone, which
prevents small uncontrolled technical factors from causing major discrepancies
in interpretation. A report of “Resistant” indicates that the pathogen is not
likely to be inhibited if the antimicrobial compound in the blood reaches the
concentrations usually achievable; other therapy should be
selected. Standardized susceptibility test procedures require the use of
laboratory control microorganisms to control the technical aspects of the
laboratory procedures. Standard ampicillin powder should
provide the following MIC values:
Microorganism
MIC Range
(mcg/mL)
E.
coli ATCC 25922
2 to 8
E. faecalis
ATCC 29212
0.5 to 2
H. influenzae
ATCC 49247d
2 to 8
S.
aureus ATCC 29213
0.25 to
1
Using amoxicillin to
determine susceptibility:
Microorganism
MIC Range
(mcg/mL)
S. pneumoniae
ATCC 49619e
0.03 to
0.12
d. This quality control range is
applicable to only H. influenzae ATCC 49247 tested by
a broth microdilution procedure using HTM.1
e. This
quality control range is applicable to only S.
pneumoniae ATCC 49619 tested by the broth microdilution procedure using
cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood.
Diffusion Techniques
Quantitative methods
that require measurement of zone diameters also provide reproducible estimates
of the susceptibility of bacteria to antimicrobial compounds. One such
standardized procedure2 requires the use of standardized
inoculum concentrations. This procedure uses paper disks impregnated with 10 mcg
ampicillin to test the susceptibility of microorganisms, except S. pneumoniae, to amoxicillin. Interpretation involves
correlation of the diameter obtained in the disk test with the MIC for ampicillin. Reports from the laboratory providing
results of the standard single-disk susceptibility test with a 10 mcg ampicillin
disk should be interpreted according to the following criteria:
For
Gram-Positive Aerobes
Enterococcus
Zone
Diameter (mm)
Interpretation
≥17
Susceptible (S)
≤16
Resistant (R)
Staphylococcus
f
Zone
Diameter (mm)
Interpretation
≥29
Susceptible (S)
≤28
Resistant (R)
β-hemolytic streptococci
Zone
Diameter (mm)
Interpretation
≥26
Susceptible (S)
19 to 25
Intermediate (I)
≤18
Resistant (R)
NOTE: For streptococci (other than β-hemolytic
streptococci and S. pneumoniae), an ampicillin MIC should be determined.
S. pneumoniae
S.
pneumoniae should be tested using a 1 mcg oxacillin disk. Isolates with
oxacillin zone sizes of ≥20 mm are susceptible to amoxicillin. An amoxicillin
MIC should be determined on isolates of S. pneumoniae
with oxacillin zone sizes of ≤19 mm. For Gram-Negative
Aerobes Enterobacteriaceae
Zone
Diameter (mm)
Interpretation
≥17
Susceptible (S)
14 to 16
Intermediate (I)
≤13
Resistant (R)
H. influenzae
g
Zone
Diameter (mm)
Interpretation
≥22
Susceptible (S)
19 to 21
Intermediate (I)
≤18
Resistant (R)
f.
Staphylococci which are susceptible to amoxicillin but resistant to
methicillin/oxacillin should be considered as resistant to amoxicillin.g.
These interpretive standards are applicable only to disk diffusion
susceptibility tests with H. influenzae using Haemophilus Test Medium (HTM).2
Interpretation should be as stated above for results
using dilution techniques. As with standard dilution techniques, disk
diffusion susceptibility test procedures require the use of laboratory control
microorganisms. The 10 mcg ampicillin disk should
provide the following zone diameters in these laboratory test quality control
strains:
Microorganism
Zone Diameter
(mm)
E.
coli ATCC 25922
16 to 22
H.
influenzae ATCC 49247h
13 to 21
S.
aureus ATCC 25923
27 to
35
Using 1 mcg oxacillin disk:
Microorganism
Zone Diameter
(mm)
S.
pneumoniae ATCC 49619i
8 to
12
h. This quality control range is applicable
to only H. influenzae ATCC 49247 tested by a disk
diffusion procedure using HTM.2
i. This quality
control range is applicable to only S. pneumoniae
ATCC 49619 tested by a disk diffusion procedure using Mueller-Hinton agar
supplemented with 5% sheep blood and incubated in 5% CO2.
Susceptibility Testing for Helicobacter pylori
In
vitrosusceptibility testing methods and diagnostic products currently
available for determining minimum inhibitory concentrations (MICs) and zone
sizes have not been standardized, validated, or approved for testing H. pylori microorganisms. Culture and
susceptibility testing should be obtained in patients who fail triple therapy.
If clarithromycin resistance is found, a non-clarithromycin-containing regimen
should be used.
Indications And Usage
Amoxicillin is indicated in the treatment of infections due to susceptible (ONLY
β-lactamase–negative) strains of the designated microorganisms in the conditions
uled below:
Infections of the ear, nose, and throat
– due to Streptococcus spp. (α- and
β-hemolytic strains only), S. pneumoniae, Staphylococcus spp., or H.
influenzae.
Infections of the genitourinary tract
– due to E. coli, P. mirabilis, or E. faecalis.
Infections of the skin
and skin structure – due to Streptococcus spp.
(α- and β-hemolytic strains only), Staphylococcus
spp., or E. coli.
Infections
of the lower respiratory tract – due to Streptococcus spp. (α- and β-hemolytic strains only), S. pneumoniae, Staphylococcus spp., or H. influenzae.
Gonorrhea, acute
uncomplicated (ano-genital and urethral infections) – due to N. gonorrhoeae (males and females).H. pylori eradication to reduce the risk of duodenal ulcer
recurrence
Triple Therapy
Amoxicillin/clarithromycin/lansoprazole
Amoxicillin,
in combination with clarithromycin plus lansoprazole as triple therapy, is
indicated for the treatment of patients with H.
pylori infection and duodenal ulcer disease (active or 1-year history of
a duodenal ulcer) to eradicate H. pylori. Eradication
of H. pylori has been shown to reduce the risk of
duodenal ulcer recurrence. (See CLINICAL
STUDIES and DOSAGE AND
ADMINISTRATION.)
Dual Therapy
Amoxicillin/lansoprazole
Amoxicillin, in
combination with lansoprazole delayed-release capsules as dual therapy, is
indicated for the treatment of patients with H.
pylori infection and duodenal ulcer disease (active or 1-year history of
a duodenal ulcer) who are either allergic or intolerant to
clarithromycin or in whom resistance to clarithromycin is known or
suspected. (See the clarithromycin package insert, MICROBIOLOGY.)
Eradication of H. pylori has been shown to reduce the
risk of duodenal ulcer recurrence. (See CLINICAL STUDIES and DOSAGE AND ADMINISTRATION.)
To reduce the
development of drug-resistant bacteria and maintain the effectiveness of
amoxicillin and other antibacterial drugs, amoxicillin should be used only to
treat or prevent infections that are proven or strongly suspected to be caused
by susceptible bacteria. When culture and susceptibility information are
available, they should be considered in selecting or modifying antibacterial
therapy. In the absence of such data, local epidemiology and susceptibility
patterns may contribute to the empiric selection of therapy. Indicated
surgical procedures should be performed.
Contraindications
A history of allergic reaction to any of the penicillins is a contraindication.
Warnings
SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE
BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. ALTHOUGH ANAPHYLAXIS IS MORE
FREQUENT FOLLOWING PARENTERAL THERAPY, IT HAS OCCURRED IN PATIENTS ON ORAL
PENICILLINS. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A
HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO
MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF
PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED
WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH AMOXICILLIN, CAREFUL INQUIRY
SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS,
CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, AMOXICILLIN
SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT
WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING
INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.
Clostridium difficile associated diarrhea (CDAD)
has been reported with use of nearly all antibacterial agents, including
amoxicillin, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon leading
to overgrowth of C. difficile.
C. difficile produces toxins A and B which
contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as
these infections can be refractory to antimicrobial therapy and may require
colectomy. CDAD must be considered in all patients who present with diarrhea
following antibiotic use. Careful medical history is necessary since CDAD has
been reported to occur over two months after the administration of antibacterial
agents. If CDAD is suspected or confirmed, ongoing antibiotic use not
directed against C. difficile may need to be
discontinued. Appropriate fluid and electrolyte management, protein
supplementation, antibiotic treatment of C.
difficile, and surgical evaluation should be instituted as clinically
indicated.
Precautions
General
The possibility of superinfections with mycotic or bacterial
pathogens should be kept in mind during therapy. If superinfections occur,
amoxicillin should be discontinued and appropriate therapy instituted. A
high percentage of patients with mononucleosis who receive ampicillin develop an
erythematous skin rash. Thus, ampicillin-class antibiotics should not be
administered to patients with mononucleosis. Prescribing amoxicillin in
the absence of a proven or strongly suspected bacterial infection or a
prophylactic indication is unlikely to provide benefit to the patient and
increases the risk of the development ofdrug-resistant bacteria.
Laboratory Tests
As with any potent drug, periodic assessment of
renal, hepatic, and hematopoietic function should be made during prolonged
therapy. All patients with gonorrhea should have a serologic test for
syphilis at the time of diagnosis. Patients treated with amoxicillin should have
a follow-up serologic test for syphilis after 3 months.
Drug Interactions
Probenecid decreases the renal tubular secretion
of amoxicillin. Concurrent use of amoxicillin and probenecid may result in
increased and prolonged blood levels of amoxicillin. Chloramphenicol,
macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal
effects of penicillin. This has been demonstrated in
vitro; however, the clinical significance of this interaction is not well
documented. In common with other antibiotics, amoxicillin may affect the
gut flora, leading to lower estrogen reabsorption and reduced efficacy of
combined oral estrogen/progesterone contraceptives.
Drug/Laboratory Test Interactions
High urine concentrations of
ampicillin may result in false-positive reactions when testing for the presence
of glucose in urine using CLINITEST®, Benedict’s
Solution, or Fehling’s Solution. Since this effect may also occur with
amoxicillin, it is recommended that glucose tests based on enzymatic glucose
oxidase reactions (such as CLINISTIX®) be
used. Following administration of ampicillin to pregnant women, a
transient decrease in plasma concentration of total conjugated estriol,
estriol-glucuronide, conjugated estrone, and estradiol has been noted. This
effect may also occur with amoxicillin.
Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate
carcinogenic potential. Studies to detect mutagenic potential of amoxicillin
alone have not been conducted; however, the following information is available
from tests on a 4:1 mixture of amoxicillin and potassium clavulanate.
Amoxicillin and potassium clavulanate was non-mutagenic in the Ames bacterial
mutation assay, and the yeast gene conversion assay. Amoxicillin and potassium
clavulanate was weakly positive in the mouse lymphoma assay, but the trend
toward increased mutation frequencies in this assay occurred at doses that were
also associated with decreased cell survival. Amoxicillin and potassium
clavulanate was negative in the mouse micronucleus test, and in the dominant
lethal assay in mice. Potassium clavulanate alone was tested in the Ames
bacterial mutation assay and in the mouse micronucleus test, and was negative in
each of these assays. In a multi-generation reproduction study in rats, no
impairment of fertility or other adverse reproductive effects were seen at doses
up to 500 mg/kg (approximately 3 times the human dose in mg/m2).
Pregnancy
Teratogenic Effects Pregnancy Category B.
Reproduction studies have been performed in mice and rats at doses up to 10
times the human dose and have revealed no evidence of impaired fertility or harm
to the fetus due to amoxicillin. There are, however, no adequate and
well-controlled studies in pregnant women. Because animal reproduction studies
are not always predictive of human response, this drug should be used during
pregnancy only if clearly needed.
Labor and Delivery
Oral ampicillin-class antibiotics are poorly
absorbed during labor. Studies in guinea pigs showed that intravenous
administration of ampicillin slightly decreased the uterine tone and frequency
of contractions but moderately increased the height and duration of
contractions. However, it is not known whether use of amoxicillin in humans
during labor or delivery has immediate or delayed adverse effects on the fetus,
prolongs the duration of labor, or increases the likelihood that forceps
delivery or other obstetrical intervention or resuscitation of the newborn will
be necessary.
Nursing Mothers
Penicillins have been shown to be excreted in human
milk. Amoxicillin use by nursing mothers may lead to sensitization of infants.
Caution should be exercised when amoxicillin is administered to a nursing
woman.Pediatric Use
Because of incompletely developed renal function in
neonates and young infants, the elimination of amoxicillin may be delayed.
Dosing of amoxicillin should be modified in pediatric patients 12 weeks or
younger (≤3 months). (See DOSAGE AND
ADMINISTRATION: Neonates and Infants.)
Geriatric Use
An analysis of clinical studies of amoxicillin was
conducted to determine whether subjects aged 65 and over respond differently
from younger subjects. Of the 1,811 subjects treated with capsules of
amoxicillin, 85% were less than 60 years old, 15% were ≥61 years old and 7% were ≥71
years old. This analysis and other reported clinical experience have not
identified differences in responses between the elderly and younger patients,
but a greater sensitivity of some older individuals cannot be ruled
out. This drug is known to be substantially excreted by the kidney, and
the risk of toxic reactions to this drug may be greater in patients with
impaired renal function. Because elderly patients are more likely to have
decreased renal function, care should be taken in dose selection, and it may be
useful to monitor renal function.
Information for Patients
Amoxicillin may be taken every 8 hours or
every 12 hours, depending on the strength of the product
prescribed. Patients should be counseled that antibacterial drugs,
including amoxicillin, should only be used to treat bacterial infections. They
do not treat viral infections (e.g., the common cold). When amoxicillin is
prescribed to treat a bacterial infection, patients should be told that although
it is common to feel better early in the course of therapy, the medication
should be taken exactly as directed. Skipping doses or not completing the full
course of therapy may: (1) decrease the effectiveness of the immediate
treatment, and (2) increase the likelihood that bacteria will develop resistance
and will not be treatable by amoxicillin or other antibacterial drugs in the
future. Diarrhea is a common problem caused by antibiotics which usually
ends when the antibiotic is discontinued. Sometimes after starting treatment
with antibiotics, patients can develop watery and bloody stools (with or without
stomach cramps and fever) even as late as 2 or more months after having taken
the last dose of the antibiotic. If this occurs, patients should contact their
physician as soon as possible.
Adverse Reactions
As with other penicillins, it may be expected that untoward reactions will be
essentially limited to sensitivity phenomena. They are more likely to occur in
individuals who have previously demonstrated hypersensitivity to penicillins and
in those with a history of allergy, asthma, hay fever, or urticaria. The
following adverse reactions have been reported as associated with the use of
penicillins:
Infections and
Infestations
Mucocutaneous candidiasis.
Gastrointestinal
Nausea, vomiting, diarrhea,
black hairy tongue, and hemorrhagic/pseudomembranous colitis. Onset of
pseudomembranous colitis symptoms may occur during or after antibiotic
treatment. (See WARNINGS.)
Hypersensitivity Reactions
Anaphylaxis (See
WARNINGS.) Serum
sickness–like reactions, erythematous maculopapular rashes, erythema multiforme,
Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis,
acute generalized exanthematous pustulosis, hypersensitivity vasculitis and
urticaria have been reported.
NOTE: These
hypersensitivity reactions may be controlled with antihistamines and, if
necessary, systemic corticosteroids. Whenever such reactions occur, amoxicillin
should be discontinued unless, in the opinion of the physician, the condition
being treated is life-threatening and amenable only to amoxicillin therapy.
Liver
A moderate rise in AST (SGOT) and/or ALT
(SGPT) has been noted, but the significance of this finding is unknown. Hepatic
dysfunction including cholestatic jaundice, hepatic cholestasis and acute
cytolytic hepatitis have been reported.
Renal
Crystalluria has also been reported (see
OVERDOSAGE).
Hemic and Lymphatic Systems
Anemia, including
hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia,
leukopenia, and agranulocytosis have been reported during therapy with
penicillins. These reactions are usually reversible on discontinuation of
therapy and are believed to be hypersensitivity phenomena.
Central Nervous System
Reversible
hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral
changes, and/or dizziness have been reported rarely.
Miscellaneous
Tooth discoloration (brown,
yellow, or gray staining) has been rarely reported. Most reports occurred in
pediatric patients. Discoloration was reduced or eliminated with brushing or
dental cleaning in most cases.
Combination Therapy with
Clarithromycin and Lansoprazole
In clinical trials using
combination therapy with amoxicillin plus clarithromycin and lansoprazole, and
amoxicillin plus lansoprazole, no adverse reactions peculiar to these drug
combinations were observed. Adverse reactions that have occurred have been
limited to those that had been previously reported with amoxicillin,
clarithromycin, or lansoprazole.
Triple Therapy
Amoxicillin/Clarithromycin/Lansoprazole
The most
frequently reported adverse events for patients who received triple therapy were
diarrhea (7%), headache (6%), and taste perversion (5%). No treatment-emergent
adverse events were observed at significantly higher rates with triple therapy
than with any dual therapy regimen.
Dual Therapy
Amoxicillin/Lansoprazole
The most frequently
reported adverse events for patients who received amoxicillin three times daily
plus lansoprazole three times daily dual therapy were diarrhea (8%) and headache
(7%). No treatment-emergent adverse events were observed at significantly higher
rates with amoxicillin three times daily plus lansoprazole three times daily
dual therapy than with lansoprazole alone. For more information on
adverse reactions with clarithromycin or lansoprazole, refer to their package
inserts, ADVERSE REACTIONS.
Overdosage
In case of overdosage, discontinue medication, treat symptomatically, and
institute supportive measures as required. If the overdosage is very recent and
there is no contraindication, an attempt at emesis or other means of removal of
drug from the stomach may be performed. A prospective study of 51 pediatric
patients at a poison-control center suggested that overdosages of less than 250
mg/kg of amoxicillin are not associated with significant clinical symptoms and
do not require gastric emptying.3
Interstitial
nephritis resulting in oliguric renal failure has been reported in a small
number of patients after overdosage with amoxicillin. Crystalluria, in
some cases leading to renal failure, has also been reported after amoxicillin
overdosage in adult and pediatric patients. In case of overdosage, adequate
fluid intake and diuresis should be maintained to reduce the risk of amoxicillin
crystalluria. Renal impairment appears to be reversible with cessation
of drug administration. High blood levels may occur more readily in patients
with impaired renal function because of decreased renal clearance of
amoxicillin. Amoxicillin may be removed from circulation by hemodialysis.
Dosage And Administration
Capsules, chewable tablets, and oral suspensions of amoxicillin may be given
without regard to meals. The 400 mg suspension, 400 mg chewable tablet, and the
875 mg tablet have been studied only when administered at the start of a light
meal. However, food effect studies have not been performed with the 200 mg and
500 mg formulations.
Neonates and Infants Aged ≤12 Weeks
(≤3 Months)
Due to incompletely developed renal function
affecting elimination of amoxicillin in this age group, the recommended upper
dose of amoxicillin is 30 mg/kg/day divided q12h.
Adults
and Pediatric Patients >3 Months
Infection
Severity *
Usual Adult Dose
Usual Dose for Children
>3 Months†‡
Ear/Nose/Throat
Mild/Moderate
500 mg every 12 hours
25 mg/kg/day in divided
or
doses every 12 hours
250 mg every 8 hours
or
20 mg/kg/day in divided
doses every 8 hours
Severe
875 mg every 12 hours
45 mg/kg/day in divided
or
doses every 12 hours
500 mg every 8 hours
or
40 mg/kg/day in divided
doses every 8 hours
Lower Rispiratory Tract
Mild/Moderate or Severe
875 mg every 12 hours
45 mg/kg/day in divided
or
doses every 12 hours
500 mg every 8 hours
or
40 mg/kg/day in divided
doses every 8 hours
Skin/Skin Structure
Mild/Moderate
500 mg every 12 hours
25 mg/kg/day in divided
or
doses every 12 hours
250 mg every 8 hours
or
20 mg/kg/day in divided
doses every 8 hours
Severe
875 mg every 12 hours
45 mg/kg/day in divided
or
doses every 12 hours
500 mg every 8 hours
or
40 mg/kg/day in divided
doses every 8 hours
Genitourinary Tract
Mild/Moderate
500 mg every 12 hours
25 mg/kg/day in divided
or
doses every 12 hours
250 mg every 8 hours
or
20 mg/kg/day in divided
doses every 8 hours
Severe
875 mg every 12 hours
45 mg/kg/day in divided
or
doses every 12 hours
500 mg every 8 hours
or
40 mg/kg/day in divided
doses every 8 hours
Gonorrhea Acute,
3 grams as single oral
Prepubertal children:
uncomplicated
dose
50 mg/kg amoxicillin,
ano-genital and
combined with 25 mg/kg
urethral infections
probenecid as a single
in males
and females
dose.
NOTE: SINCE
PROBENECID IS
CONTRAINDICATED
IN CHILDREN UNDER
2 YEARS, DO NOT USE
THIS REGIMEN IN
THESE CASES.
* Dosing for infections caused by less susceptible organisms should follow the
recommendations for severe infections.
† The
children’s dosage is intended for individuals whose weight is less than 40 kg.
Children weighing 40 kg or more should be dosed according to the adult
recommendations.
‡ Each strength of the suspension of
amoxicillin is available as a chewable tablet for use by older children.All patients with gonorrhea should be evaluated for syphilis. (See PRECAUTIONS: Laboratory
Tests.) Larger doses may be required for stubborn or severe
infections.
General
It should be
recognized that in the treatment of chronic urinary tract infections, frequent
bacteriological and clinical appraisals are necessary. Smaller doses than those
recommended above should not be used. Even higher doses may be needed at times.
In stubborn infections, therapy may be required for several weeks. It may be
necessary to continue clinical and/or bacteriological follow-up for several
months after cessation of therapy. Except for gonorrhea, treatment should be
continued for a minimum of 48 to 72 hours beyond the time that the patient
becomes asymptomatic or evidence of bacterial eradication has been obtained. It
is recommended that there be at least 10 days’ treatment for any infection
caused by Streptococcus pyogenes to prevent the
occurrence of acute rheumatic fever.H. pylori Eradication to Reduce the
Risk of Duodenal Ulcer Recurrence
Triple Therapy
Amoxicillin/clarithromycin/lansoprazole
The
recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30
mg lansoprazole, all given twice daily (q12h) for 14 days. (See INDICATIONS AND USAGE.)
Dual
Therapy
Amoxicillin/lansoprazole
The
recommended adult oral dose is 1 gram amoxicillin and 30 mg lansoprazole, each
given three times daily (q8h) for 14 days. (See INDICATIONS AND USAGE.) Please refer to
clarithromycin and lansoprazole full prescribing information for
CONTRAINDICATIONS and WARNINGS, and for information regarding dosing in elderly
and renally impaired patients.
Dosing Recommendations
for Adults with Impaired Renal Function
Patients with impaired
renal function do not generally require a reduction in dose unless the
impairment is severe. Severely impaired patients with a glomerular filtration
rate of less than 30 mL/min. should not receive the 875 mg tablet. Patients with a
glomerular filtration rate of 10 to 30 mL/min. should receive 500 mg or 250 mg
every 12 hours, depending on the severity of the infection. Patients with a less
than 10 mL/min. glomerular filtration rate should receive 500 mg or 250 mg every
24 hours, depending on severity of the infection. Hemodialysis patients
should receive 500 mg or 250 mg every 24 hours, depending on severity of the
infection. They should receive an additional dose both during and at the end of
dialysis.
There are currently no dosing recommendations
for pediatric patients with impaired renal function.
How Supplied
Amoxicillin Tablets, USP contains 875 mg amoxicillin as
the trihydrate.
875 mg Tablet
Pink
colored, capsule shaped, film coated tablets debossed with “A” on one side and
with a score line in between “6” and “7” on the other
side. Bottles of 20 NDC
59762-1050-2 Bottles of 100 NDC
59762-1050-5
Store at 20° to 25°C (68° to 77°F);
excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room
Temperature].
Dispense in a tight container.
Clinical Studies
H. pylori
Eradication to Reduce the Risk of Duodenal Ulcer
Recurrence
Randomized, double-blind clinical studies performed in
the United States in patients with H. pylori and
duodenal ulcer disease (defined as an active ulcer or history of an ulcer within
1 year) evaluated the efficacy of lansoprazole in combination with amoxicillin
capsules and clarithromycin tablets as triple 14-day therapy, or in combination
with amoxicillin capsules as dual 14-day therapy, for the eradication of H. pylori. Based on the results of these studies, the
safety and efficacy of 2 different eradication regimens were
established:
Triple Therapy Amoxicillin 1 gram twice
daily/clarithromycin 500 mg twice daily/lansoprazole 30 mg twice
daily.
Dual Therapy Amoxicillin 1 gram three times
daily/lansoprazole 30 mg three times daily. All treatments were for 14
days. H. pylori eradication was defined as 2 negative
tests (culture and histology) at 4 to 6 weeks following the end of
treatment. Triple therapy was shown to be more effective than all
possible dual therapy combinations. Dual therapy was shown to be more effective
than both monotherapies. Eradication of H. pylori has
been shown to reduce the risk of duodenal ulcer recurrence.
H. pylori Eradication Rates – Triple Therapy
(amoxicillin/clarithromycin/lansoprazole) Percent of Patients Cured [95%
Confidence Interval] (Number of Patients)
Study
Triple Therapy
Triple Therapy
Evaluable Analysis *
Intent-to-Treat Analysis †
Study 1
92‡
86‡
[80 - 97.7]
[73.3 - 93.5]
(n = 48)
(n = 55)
Study 2
86§
83§
[75.7 - 93.6]
[72 - 90.8]
(n = 66)
(n = 70)
* This analysis was based on evaluable patients with confirmed duodenal ulcer
(active or within 1 year) and H. pylori infection at
baseline defined as at least 2 of 3 positive endoscopic tests from CLOtest®, (Delta West Ltd., Bentley, Australia), histology, and/or
culture. Patients were included in the analysis if they completed the study.
Additionally, if patients dropped out of the study due to an adverse event
related to the study drug, they were included in the analysis as failures of
therapy.
† Patients were included in the analysis if
they had documented H. pylori infection at baseline
as defined above and had a confirmed duodenal ulcer (active or within 1 year).
All dropouts were included as failures of therapy.
‡
(p less than 0.05) versus lansoprazole/amoxicillin and lansoprazole/clarithromycin dual
therapy.
§ (p less than 0.05) versus
clarithromycin/amoxicillin dual therapy.
H. pylori Eradication Rates – Dual Therapy (amoxicillin/lansoprazole) Percent of
Patients Cured [95% Confidence Interval] (Number of Patients)
Study
Dual Therapy
Dual Therapy
Evaluable Analysis *
Intent-to-Treat Analysis †
Study 1
77‡
70‡
[62.5 - 87.2]
[56.8 - 81.2]
(n = 51)
(n = 60)
Study 2
66§
61§
[51.9 - 77.5]
[48.5 - 72.9]
(n = 58)
(n = 67)
* This analysis was based on evaluable patients with confirmed duodenal ulcer
(active or within 1 year) and H. pylori infection at
baseline defined as at least 2 of 3 positive endoscopic tests from CLOtest®, histology, and/or culture. Patients were included in the
analysis if they completed the study. Additionally, if patients dropped out of
the study due to an adverse event related to the study drug, they were included
in the analysis as failures of therapy.
† Patients
were included in the analysis if they had documented H.
pylori infection at baseline as defined above and had a confirmed
duodenal ulcer (active or within 1 year). All dropouts were included as failures
of therapy.
‡ (p less than 0.05) versus lansoprazole
alone.
§ (pless than 0.05) versus lansoprazole alone or
amoxicillin alone.
References
National Committee for Clinical Laboratory Standards. Methods for Dilution
Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically – Fourth
Edition; Approved Standard NCCLS Document M7-A4, Vol. 17, No. 2. NCCLS, Wayne,
PA, January 1997.
National Committee for Clinical Laboratory Standards. Performance Standards
for Antimicrobial Disk Susceptibility Tests – Sixth Edition; Approved Standard
NCCLS Document M2-A6, Vol. 17, No. 1. NCCLS, Wayne, PA, January 1997.
Swanson-Biearman B, Dean BS, Lopez G, Krenzelok EP. The effects of
penicillin and cephalosporin ingestions in children less than six years of age.
Vet Hum Toxicol. 1988;30:66-67.
CLINITEST is a registered trademark of Miles,
Inc.CLINISTIX is a registered trademark of Bayer Corporation.CLOtest is
a registered trademark of Kimberly-Clark Corporation.
GREENSTONE® BRAND
Distributed by:
Greenstone LLC
Peapack, NJ
07977 Code No.: DRUGS/AP/57/2003 Revised: 11/2008
Package Label - Amoxicillin 875 Mg Tablet
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The amoxicillin molecular formula is C16H19N3O5S•3H2O, and the molecular weight is 419.45. Tablets of amoxicillin are intended for oral administration. Each film coated tablet contains 875 mg amoxicillin as the trihydrate. The 875 mg Pink colored, capsule shaped, film coated tablets debossed with “A” on one side and with a score line in between “6” and “7” on the other side. Inactive ingredients: Colloidal silicon dioxide, crospovidone, D and C Red No. 30 aluminum lake, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, and titanium dioxide.
