AMOXICILLIN
-
amoxicillin capsule
Apotheca Inc.
AMOXICILLIN 250MG CAPSULES USP
AMOXICILLIN 500MG CAPSULES USP
Rx OnlyDESCRIPTION
Formulations of amoxicillin capsules, 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 (2
S,5
R,6
R)-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 C
16H
19N
3O
5S•3H
2O, and the molecular weight is 419.45.
Capsules of
amoxicillin are intended for oral administration.
Each capsule of
amoxicillin with blue cap and pink body, contains 250 mg or 500 mg amoxicillin
as the trihydrate. The body of the 250 mg capsule is imprinted with ‘A44’ in
black ink. The body of the 500 mg capsule is imprinted with ‘A45’ in black
ink. Inactive ingredients: microcrystalline cellulose, D and C Red No. 28,
FD and C Blue No. 1, FD and C Red No. 40, gelatin, magnesium stearate, titanium
dioxide, and sodium lauryl sulfate.
Meets USP Dissolution Test 2.
CLINICAL PHARMACOLOGY
Amoxicillin is stable in the presence of gastric acid and is
rapidly absorbed after oral administration. 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.
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 pyloriSusceptibility 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 method
1 (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)
|
Staphylococcusa
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.
pneumoniaeb 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.
influenzaec
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.
1e. 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 procedure
2 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)
|
Staphylococcusf
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. pneumoniaeshould 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.
influenzaeg
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.
2i. 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% CO
2.Susceptibility Testing for Helicobacter pylori
In vitro susceptibility 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
listed 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 of drug-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/m
2).
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 percent were younger than 60 years old, 15 percent were older than 61 years old and 7 percent were over 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 eldery 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:
Gastrointestinal: Nausea,
vomiting, diarrhea, and hemorrhagic / pseudomembranous colitis.
Onset of pseudomembranous colitis symptoms may occur during or after
antibiotic treatment. (See WARNINGS.)
Hypersensitivity
Reactions: 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 3 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 3 times
daily plus lansoprazole 3 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 over-dosage 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
Amoxicillin capsules, chewable tablets, and oral suspensions 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.
Amoxicillin tablets, chewable should be chewed before swallowing
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§ π |
Ear/Nose/Throat |
Mild/Moderate |
500 mg every12 hours or 250 mg every 8 hours |
25 mg/kg/day in divided doses every 12 hours
or 20 mg/kg/day in divided doses every 8 hours |
|
Severe |
875 mg every 12 hours or 500 mg every 8 hours |
45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours |
Lower Respiratory Tract |
Mild/Moderate or Severe |
875 mg every 12 hours or 500 mg every 8 hours |
45 mg/kg/day in divided doses every 12 hours
or 40 mg/kg/day in divided doses every 8 hours |
Skin/Skin Structure |
Mild/Moderate |
500 mg every12 hours or 250 mg every 8 hours |
25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours |
|
Severe |
875 mg every12 hours or 500 mg every 8 hours |
45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours |
Genitourinary Tract |
Mild/Moderate |
500 mg every12 hours or 250 mg every 8 hours |
25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours |
|
Severe |
875 mg every12 hours or 500 mg every 8 hours |
45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours |
Gonorrhea Acute, uncomplicated ano-genital and urethral
infections in males and females |
|
3 grams as single oral dose |
Prepubertal children: 50 mg/kg
amoxicillin, combined with 25 mg/kg probenecid as a single 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.
π Each strength of the suspension of amoxicillin is
available as a chewable tablet for use by older children.
After reconstitution, the required amount of suspension should be placed
directly on the child’s tongue for swallowing. Alternate means of administration
are to add the required amount of suspension to formula, milk, fruit juice,
water, ginger ale, or cold drinks. These preparations should then be taken
immediately. To be certain the child is receiving full dosage, such preparations
should be consumed in entirety.
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 TherapyAmoxicillin/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 TherapyAmoxicillin/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 Capsules, USP contains 250 mg or 500 mg
amoxicillin as the trihydrate.
250 mg Capsule Blue/Pink size “1” hard gelatin capsule filled with white to off white
granular powder and imprinted with “A44” on pink body with black ink.
- NDC 12634-183-91 Blister Pack UD
- NDC 12634-183-94 Bottle of 4
- NDC 12634-183-84 Bottle of 14
- NDC 12634-183-85 bottle of 15
- NDC 12634-183-81 Bottle of 21
- NDC 12634-183-71 Bottle of 30
- NDC 12634-183-60 Bottle of 60
- NDC 12634-183-01 Bottle of 100
500 mg Capsule Blue/Pink size “0EL” hard gelatin capsule filled with white to off
white granular powder and imprinted with “A45” on pink body with black ink.
- NDC 12634-185-91 Blister Pack UD
- NDC 12634-185-94 Bottle of 4
- NDC 12634-185-96 Bottle of 6
- NDC 12634-185-99 Bottle of 9
- NDC 12634-185-84 Bottle of 14
- NDC 12634-185-85 Bottle of 15
- NDC 12634-185-81 Bottle of 21
- NDC 12634-185-71 Bottle of 30
- NDC 12634-185-60 Bottle of 60
- NDC 12634-185-01 Bottle of 100
Storage and Dispensing
Store capsules, tablets and unreconstituted powder for oral suspension at
20°-25°C (68°-77°F). [See USP Controlled Room Temperature]. Dispense in a tight
container.
CLINICAL STUDIES
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer
RecurrenceRandomized, 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) |
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) |
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.
Manufactured by: Aurobindo Pharma Limited
Manufactured for: Aurobindo Pharma USA, Inc.
Repackaged by: Sandhills Packaging, Inc. for Apotheca, Inc..
Repackaged by: Apotheca, Inc.
Distributed by: Apotheca, Inc.
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 500 mg (30 Capsule Bottle)
NDC 12634-185-71
Amoxicillin
Capsules, USP
500 mg
Rx
only 30 Capsules
NDC 12634-185-71
Amoxicillin
Capsules, USP
500 mg
Rx
only 30 Capsules
AMOXICILLIN
amoxicillin
capsule
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AMOXICILLIN
amoxicillin
capsule
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Revised: 03/2010Apotheca Inc.