(amoxicillin/clavulanate potassium)
Powder for Oral Suspension and Chewable Tablets
DESCRIPTION
CLINICAL PHARMACOLOGY
INDICATIONS AND USAGE
CONTRAINDICATIONS
WARNINGS
PRECAUTIONS
ADVERSE REACTIONS
OVERDOSAGE
DOSAGE AND ADMINISTRATION
DIRECTIONS FOR MIXING ORAL SUSPENSION
HOW SUPPLIED
CLINICAL STUDIES
REFERENCES
Augmentin is an oral antibacterial combination consisting of the semisynthetic antibiotic
amoxicillin and the B-lactamase inhibitor, clavulanate potassium (the potassium salt clavulanic
acid). Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, 6-
aminopenicillanic acid. The amoxicillin molecular formula is C16H19N3O5S · 3H2O and the
molecular weight is 419.46. Chemically, amoxicillin is (2S,5R,6R)-6-[(R)-(-)-2- (p-hydroxyphenyl)
acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0) heptane-2-carboxlic acid trihydrate and
may be represented structurally as:
Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a B-lactam
structurally related to the penicillins and possesses the ability to inactivate a wide variety of B-
lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active
against the clinically important plasmid mediated B-lactamases frequently responsible for
trasferred drug resistance to penicillins and cephalosporins. The clavulanate potassium
molecular formula is C8H8KNO5 and the molecular weight is 237.25. Chemically clavulanate
potassium is potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-
heptane-2-carboxylate and may be represented structurally as:
Inactive Ingredients: Powder for Oral Suspension-Collodial silicon dioxide, flavorings (See How
Supplied), succinic acid, xanthan gum, and one or more of the following: aspartame*, hydroxypropyl
methylcellulose, mannitol, silica gel, silicon dioxide and sodium saccharin . Chewable Tablets-Collodial silicon dioxide,
flaborings (See How Supplied), magnesium stearate, mannitol and one or more of the
following: aspartame*; D&C; yellow No.10, FD&C; Red No. 40, glycine, sodium saccharin and
succinic acid.
*See PRECAUTIONS-Information for Patients.
Each 125 mg chewable tablet and each 5 mL of reconstituted Augmentin 125 mg/5 mL oral
suspension contains 0.16 mEq potassium. Each 250 mg chewable tablet and each 5 mL of
reconstituted Augmentin 250 mg/5 mL oral suspension contains 0.32 mEq potassium. Each 200
mg chewable tablet and each 5 mL of reconstituted Augmentin 200 mg/5 mL oral suspension
contains 0.14 m Eq potassium. Each 400 mg chewable tablet and each 5 mL of reconstituted
Augmentin 400 mg/5 mL oral suspension contains 0.29 mEq of potassium
Amoxicillin and clavulanate potassium are well absorbed from the gastrointestinal tract after oral
administration of Augmentin. Dosing in the fasted or fed state has minimal effect on the
pharmacokinetics of amoxicillin. While Augmentin can be given without regard to meals,
absorption of clavulanate potassium when taken with food is greater relative to the fasted state.
In one study, the relative bioavailability of clavulanate was reduced when Augmentin was dosed
at 30 and 150 minutes after the start of a high fat breakfast. The safety and efficay of
Augmentin have been established in clinical trials where Augmentin was taken without regard to
meals.
Oral administration of single doses of 400 mg Augmentin chewable tablets and 400 mg/5 mL
suspension to 28 adult volunteers yielded comparable pharmacokinetic data:
tAdminsitered at the start of a light meal.
tMean values of 28 normal volunteers. Peak concentrations occured approximately 1 hours
after the dose.
Oral adminsitration of 5 mL of Augmentin 250 mg/5 mL suspension or the equivalent dose of 10
mL Augmentin 125 mg/5 mL suspension provides average peak serum concentrations
approximately 1 hour after dosing of 6.9 µg/mL for amoxicillin and 1.6 µg/mL for clavulanic acid.
The areas under the serum concentration curves obtained during the first 4 hours after dosing
were 12.6 µg.hr./mL for amoxicillin and 2.9 µg.hr./mL clavulanic acid when 5 mL of Augmentin 250 mg/5 mL suspension or equivalent dose of 10 mL of Augmentin 125 mg/5 mL suspension was administered to adult volunteers.
One Augmentin 250 mg chewable tablet or 2 Augmentin 125 mg chewable tablets are equivalent
to 5 mL of Augmentin 250 mg/5 mL suspension and provide similar serum levels of amoxicillin
and clavulanic acid.
Amoxicillin serum concentrations achieved with Augmentin are similar to those produced by the
oral administration of equivalent doses of amoxicillin alone. The half-life of amoxicillin after the
oral administration of Augmentin is 1.3 hours and that of clavulanic acid is
The half-life of amoxicillin after the oral administration of Augmentin is 1.3 hours and that of
clavulanic acid is 1.0 hour. Time above the minimum inhibitory concentration of 1.0 µg/mL for
amoxicillin has been shown to be similar corresponding q 12h and q 8h dosing regimens of
Augmentin in adults and children.
Approximately 50% to 70% of the amoxicillin and approximately 25% to 40% of the clavulanic
acid are excreted unchanged in urine during the first 6 hours after administration of 10 mL of
Augmentin 250 mg/5 mL suspension.
Concurrent administration of probenecid delays amoxicillin excretion but does not delay renal
excretion of clavulanic acid. Neither component in Augmentin is highly protein-bound; clavulanic
acid has been found to be approximately 25% bound to human serum and amoxicillin
approximately 18% bound.
Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and
spinal fluid. The results of experiments involving the administration of clauvulanic acid to
animals suggest that this compound, like amoxicillin, is well distributed in body tissues.
Two hours after oral administration of a single 35 mg/kg/dose of Augmentin suspension to
fasting children, average concentrations of 3.0 µg/mL of amoxicillin and 0.5 µg/mL of clavulanic
acid were detected in middle ear effustions.
Microbiology: Amoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal
activity against many gram-positime and gram-negative microorganisms. Amoxicillin is,
however, susceptible to degradation by B-lactamases and, therefore, the spectrum of activity
does not include organisms which produce these enzymes. Clavulanic acid is a B-lactam,
structurally related to the penicillins, which possesses the ability to inactivate a wide range of B-
lactamase enzymes commonly found in microorganisms resistant to penicillins and
cephalorporins. In particular, it has good activity against the clinically important plasmid
mediated B-lactamases frequently responsible for transferred drug resistance.
The formulation of amoxicillin and clavulanic acid in Augmentin protects amoxicillin from
degradation by B-lactamase enzymes and effectively extends the antibiotic spectrum of
amoxicillin to include many bacteria normally resistant to amoxicillin and other B-lactam
antibiotics. Thus, Augmentin possesses the distinctive properties of broad-spectrum antiobiotic
and a B-lactamase inhibitor.
Amoxicillin/Clavulanic acid has been shown to be active against most strains of the following
microorganiams, both in vitro and in clinical infections as described in the INDICATIONS AND
USAGE section.
Gram-Positive Aerobes
Staphylococcus aureus (B-lactamase and non-B-lactamase producing)
Staphylocci which are resistant to methicilin/Oxacillin must be considered resistant to
amoxicillin/Clavulanic acid.
Gram-Negative Aerobes
Enterobacter species (Although most strains of Enterobacter species are resistant in vitro,
clinical efficacy has been demonstrated with Augmentin in urinary tract infections caused by
these organisms.)
Escherichia coli (B-lactamase and non-B-lactamase producing)
Haemophilus influenzae (B-lactamase and non-B-lactamase producing)
Klebsiella species (All known strains are B-lactamase producing.)
Moraxella catarrhalis (B-lactamase and non-B-lactamase producing)
The following in vitro data are available, but their clinical significance is unknown.
Amoxicillin/clavulanic acid exhibits in vitro minimal inhibitory concentrations (MICs) of 0.5 pg/mL
or less against most (> or = to 90%) strains of Steptococcus pneumoniae, MICs of 0.06 pg/mL or less
against most (> or = to 90%) strains of Neisseria gonorrhoeae, MICs of 4 µg/mL or less against most
(> or = to 90%) strains of staphylococci and anaerobic bacteria; and MICs of 8 pg/mL or less against most
(> or = to 90%) strains of other listed organisms. However, with the exception of organisms shown to
respond to amoxicillin alone, the safety and effectiveness of amoxicillin/clavulanic acid in
treating clinical infections due to these microorganisms have not been established in adequate
and well-controlled clinical trials.
*Because amoxicillin has greater in vitro activity against Streptococcus pneumoniae than does
ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate susceptibility to
ampicillin or penicillin are fully susceptible to amoxicillin.
GRAM-POSITIVE AEROBES
Enterococcus faecalis
Staphylococcus epidermidis (B-lactamase and non-B-lactamase producing)
Staphylococcus saprophyticus (B-lactamase and non-lactamase producing)
Streptococcus pneumoniae
Streptococcus pyogenes
viridans group Streptococcus
GRAM-NEGATIVE AEROBES
Eikenella corrodens (Blactamase and non-B-lactamase producing)
Neisseria gonorrhoeae (B-lactamase and non-B-lactamase producing)
Proteus mirabils (B-lactamase and non-B-lactamase producing)
ANAEROBIC BACTERIA
Bacteroides species including Bacteroides fragilis (B-lactamase producing)
Fusobacterium species (B-lactamase and non-Blactamse producing)
Peptostreptococcus species
Adequate and well-controlled clinical trials have established the effectiveness of amoxicillin
alone in trating certain clinical infections due to these organisms.
These are non-B-lactamase producing organisms and, therefore, are susceptible to amoxicillin
alone.
SUCCEPTIBILITY TESTING
Dilution Techniques: Quantitative methods are used to determine antimicrobial minimal
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 (broth or agar) or equivalent with
standardized inoculum concentrations and standardized concentrations of amoxicillin/clavulanate
potassium powder.
The recommended dilution pattern utilizes a constant amoxicillin/clavulanate potassium ratio of 2
to 1 in all tubes with varying amounts of amoxicillin. MICs are expressed in terms of the
amoxicillin concentration in the presence of clavulanic acid at a constant 2 parts amoxicillin to 1
part clavulanic acid. The MIC values should be interpreted according to the following criteria:
RECOMMENDED RANGES FOR AMOXICILLIN/CLAVULANIC ACID SUSCEPTIBILITY
TESTING
For gram-negative enteric aerobes:
MIC (µg/mL) Interpretation
<= 8/4 Susceptible (S)
16/8 Intermediate (I)
>= 32/16 Resistant (R)
For Staphylooccus and Haemophilus species:
MIC (µg/mL) Interpretation
<= 4/2 Susceptible (S)
>= 8/4 Resistant (R)
Staphylococci which are susceptible to amoxicillin/clavulanic acid
but resistant to methicillin/oxacillin must be considered as resistant.
For Streptococcus pneumoniae: isolates should be tested using
amoxicillin/claulanic acid and the following criteria should be used.
MIC (ug/mL) Interpretation
<= 0.5/0.25 Susceptible (S)
1/0.5 Intermediate (I)
>= 2/1 Resistant (R)
A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial
compound in the blood reaches the concentration 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 that prevents small uncontrolled technical factors from using 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 amoxicillin/clavulanate
potassium powder should provide the following MIC values.
Microorganism MIC Range (µg/mL) Escherichia coliATCC 25922 2 to 8 Escherichia coli ATCC 35218 4 to 16 Enterococcus faecalis ATCC 29212 0.25 to 1.0 Haemophilus influenzae ATCC 49247 2 to 16 Staphylococus aureus ATCC 29213 0.12 to 0.5 Steptococcus pneumonia ATCC 49619 0.03 to 0.12
Expressed as concentration of amoxicillin in the presence of clavulanic acid at a constant 2
parts amoxicillin to 1 part clavulanic acid.
Diffusion Techniques: Quantitative methods that require measurement of zone diameters also
provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. On
such standardized procedure requires the use of standardized inoculm concentrations. This
procedure uses paper disks impregnated with 30 µg of amoxicillin/clavulanate potassium (20 µg
amoxicillin plus 10 µg clavulanate potassium) to test the susceptibility of microorganisms to
amoxicillin/clavulanic acid.
Reports from the laboratory providing results of the standard single-disk susceptibility test with a
30 µg amoxicillin/clavulanate potassium (20 µg amoxicillin plus 10 µg clavulanate potassium)
disk should be interpreted according to the following criteria:
RECOMMENDED RANGES FOR AMOXICILLIN/CLAVULANIC ACID SUSCEPTIBILITY
TESTING
For Staphylococcus* species and H. influenzaea
Zone Diameter (mm) Interpretation >= 20 Susceptible (S) <= 19 Resistant (R) For other organisms except S. pneumoniae b and N. Gonorrhoeae c Zone Diameter (mm) Interpretation >= 18 Susceptible (S) 14 to 17 Intermediate (I) <= 13 Resistant (R)
*Staphylocci which are resistant to methicillin/Oxacillin must be considered as resistant to
amoxicillin/clavulanic acid.
aA broth microdilution method should be used for testing H. Influenzae. Beta-lactamase
negative, ampicillin-resistant strains must be considered resistant to amoxicillin/clavulanic acid.
bSusceptibility of S. Pneumoniae should be determined using a 1 µg oxacillin disk. Isolates with
oxacillin zone sizes of >= 20 mm are susceptible to amoxicillin/clavulanic acid. An
amoxicillin/clavulanic acid MIC should be determined on isolates of S. pneumoniae with oxacillin
zone sizes of >= 19 mm.
cA broth microdilution method should be used for testing N. gonorrhoeae and interpreted
according to penicillin breakpoints.
Interpretation should be as stated above for results using
dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test
with the MIC for amoxicillin/clavulanic acid.
As with standardized dilution techniques, diffusion methods require the use of laboratory control
microorganisms that are used to control the technical aspects of the laboratory procedures. For
the diffusion technique, the 30 µg amoxicillin/clavulanate potassium (20 µg amoxicillin plus 10
µg clavulanate potassium) disk should provide the following zone in these laboratory quality
control strains:
Microorganism Zone Diameter (mm) Escherichia coli ATTC 25922 19 to 25 mm Escherichia coli ATCC 35218 18 to 22 mm Staphylococcus aureus ATCC 25923 28 to 36 mm
Augmentin is indicated in the treatment of infections caused by susceptible strains of the
designated organisms in the conditions listed below:
Lower Respiratory Tract Infections-caused by B-lactamase producing strains of Haemophilus
influenzae and Moraxella (Branhamella) catarrhalis.
Otis Media– caused by B-lactamase-producing strains of Haemophilus influenzae and Moraxella
(Branhamella) catarrhalis.
Sinusitis– caused by B-lactamase-producing strains of Haemophilus influenzae and Moraxella
(Branhamella) catarrhalis.
Skin and Skin Structure Infections– caused by B-lactamase producing strains of Staphlyococcus
aureus, Escherichia coli and Klebsiella spp.
Urinary Tract Infections– caused by B-lactamase-producing strains of Escherichia coli, Klebsiella
spp. and Enterobacter spp.
While Augmentin is indicated only for the conditions listed above,
infections caused by ampicillin-susceptible organisms are also amenable to Augmentin treatment
due to its amoxicillin content. Therefore, mixed infections caused by ampicillin-susceptible
organisms and B-lactamase-producing organisms susceptible to Augmentin should not require
the addition of another antibiotic. Because amoxicillin has greater in vitro activity against
Streptococcus pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae
strains with intermediate susceptibility to ampicillin or penicillin are fully susceptible to amoxicillin
and Augmentin.(See Microbiology subsection.)
Bacteriological studies, to determine the causative organisms and their susceptibility to
Augmentin, should be performed together with any indicated surgical procedures.
Therapy may be instituted prior to obtaining the results from bacteriological and susceptibility
studies to determine the causative organisms and their susceptibility toAugmentin when there is
reason to believe the infection may involve any of the B-lactamase-producing organisms listed
above. Once the results are known, therapy should be adjusted, if appropriate.
Augmentin is contraindicated in patients with a history of allergic reaction to any penicillin. It is
also contraindicated in patients with a previous history of Augmentin-associated cholestatic
jaundice/hepatic dysfunction.
SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC)
REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. 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 AUGMENTIN,
CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY
REACTIONS TO PENICILLINS, CEPHALOSPORINS OR OTHER ALLERGENS. IF AN
ALLERGIC REACTION OCCURS, AUGMENTIN SHOULD BE DISCONTINUED AND THE
APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHLACTIC REACTIONS REQUIRE
IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE, OXYGEN, INTRAVENOUS
STEROIDS AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE
ADMINISTERED AS INDICATED.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including
Augmentin and has ranged in severity from mild to life-threatening. Therefore, it is important to
consider this diagnosis in patients who present with diarrhea subsequent to the admisistration of
antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit
overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium dificile is one
primary cause of “antibiotic associated colitis.”
After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic
measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug
discontinuation alone. In moderate to severe cases, consideration should be given to
management with fluids and electrolytes, protein supplementaion and treatment with an
antibacterial drug clinically effective against Clostridium difficile colitis.
Augmentin should be used with caution in patients with evidence of hepatic dysfunction. Hepatic
toxicity associated with the used of Augmentin should be used with caution in patients with
evidence of hepatic dysfunction. Hepatic toxicity associated with the use of Augmentin is usually
reversible. On rare occasions, deaths have been reported (less than 1 death reported per
estimated 4 million prescriptions worldwide). These have generally been cases associated with
serious underlying diseases or concomitant medications. (SEE CONTRAINDICATIONS AND
ADVERSE REACTIONS-Liver.)
General. While Augmentin possesses the characteristic low toxicity of penicillin group of
antibiotics, periodic assessment of organ system functions, including renal, hepatic and
hematopoitic function, is advisable during prolonged therapy. 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.
The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind
during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug
should be discontinued and/or appropriate therapy instituted.
Information for the Patient: Augmentin may be taken every 8 hours or every 12 hours, depending on the strength of the
product prescribed. Each dose should be taken with a meal or snack to reduce the possibility of
gastrointestinal upset. Many antibiotics can cause diarrhea. If diarrhea is severe or lasts more
than 2 or 3 days, call your doctor.
Make sure your child completes the entire prescribed course of treatment, even if he/she begins
to feel better after a few days. Keep suspension refrigerated. Shake well before using. When
dosing a child with Augmentin suspension (liquid), use a dosing spoon or medicine dropper.Be sure to rinse the spoon or dropper after each use. Bottles of Augmentin suspension may contain more liquid than required. Follow your
doctor’s instructions about the amount to use and the days of treatment your child requires.
Discard any unused medicine.
Phenylketonurics: Each 200 mg Augmentin chewable tablet contains 2.1 mg phenylalanine,
each 400 mg chewable tablet contains 4.2 mg phenylalanine: each 5 mL of either the 200 mg/5
mL or 400 mg/5mL oral suspension contains 7 mg phenylalanine. The other Augmentin products
do not contain phenylalanine and can be used by phenylketonurics. Contact your physician or
pharmacist.
Drug Interactions: Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent
use with Augmentin may result in increased and prolonged blood levels of amoxicillin. Co-
administration of probenecid cannot be recommended.
The concurrent administration of allopurinol and ampicillin increases substantially the incidence
of rashes of patients receiving both drugs as compared to patients receiving ampicillin alone. It
is not known whether this potentiation of ampicillin rashes is due to allopurinol or the
hyperuricemia presents in these patients. There are no data with Augmentin and allopurinol
administered concurrently.
Drug/Laboratory Test Interactions: Oral administration of Augmentin will result in high urine
concentrations of amoxicillin. 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 Dolution. Since this effect may also occur with amoxicillin and therefore Augmentin, it
is recommended that glucose tests based on enzymatic glucose exidase reactions (such as
Clinistix® or Tes-Tape®) 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
and therefore Augmentin.
Carcinogenesis, Mutagenesis, Impariment of Fertility: Long-term studies in animals have not
been performed to evaluate carcinogenic potential.
Mutagenesis: The mutagenic potential of Augmentin was investigated in vitro with an Ames test,
a human lymphocyte cytogenetic assay, a yeast test and mouse lymphoma forward mutation
assay, and where weak activity was found at very high, cytotoxic concentrations.
Impairment of Fertility: Augmentin at oral doses of up to 1200 mg/kg/day (5.7 times the
maximum human dose, 1480 mg/m2/day, based on body surface area) was found to have no
effect on fertility and reproductive performance in rats, dosed with a 2:1 ratio formulation of
amoxicillin:clavulanante.
Teratogenic effects: Pregnancy (catagory B): Reproduction studies performed in pregnant rats
and mice given augmentin at oral dosages up to 1200 mg/kg/day, equivalent to 7200 and 4080
mg/m2/day, respectively (4.9 and 2.8 times the maximum human oral dose based on body
surface area), revealed no evidence of harm to the fetus due to Augmentin. There are, however,
no adequate and well-continued 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 generally poorly absorbed during labor.
Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the
uterine tone. Frequency of contractions, height of contractions and duration of contractions.
However, it is not known whether the use of Augmentin 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 resusciation of the newborn
will be necessary.
Nursing Mothers: Ampicillin class antibiotics are excreted in the milk, therefore, caution should
be exercised when Augmentin 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 Augmentin should be modified
in pediatric patients younger than 12 weeks (3 months). (See DOSAGE AND
ADMINISTRATION-pediatric.)
Augmentinis generally well tolerated. The majority of side effects observed in clinical trials were
of a mild and transient nature and less than 3 % of patients discontinued therapy because of
drug-related side effects. From the original premarketing studies, where both pediatric and adult
patients were enrolled, the most frequently reported adverse effects were diarrhea/loose stools
(9%), nausea (3%), skin rashed and urticaria, (3%) vomiting (1%) and vaginitis (1%). The
overall incidence of side effects, and in particular diarrhea, increased with the higher
recommended dose. Other less fequently reported reactions include: abdominal discomfort,
flatulence and headache.
In pediatric patients (aged 2 months to 12 years), one U.S/Canadian clinical trial was conducted
which compared Augmentin 45/6.4 mg/kg/day (divided q12h) for 10 days versus Augmentin
40/10 mg/kg/day divided q8h) 10 days in treatment of acute otitis media. A total of 575 patients
were enrolled, and only the suspension formulations were used in this trial. Overall, the adverse
event profile seen was comparable to that noted aboce. However, there were differences in the
rates of diarrhea, skin rashes/urticaria, and diaper area rashes.(See CLINICAL STUDIES)
The following adverse reactions have been reported for ampicillin class antibiotics:
Gastrointestinal: Diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black
“hairy” tongue, enterocolitis, mucocutaneous candidiasis and pseudomembranous colitis. Onset
of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (See
WARNINGS)
Hypersensitivity Reactions: Skin rashes, pruritus, urticaria, angiodema, serum sickness like
reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia and frequently fever),
erythema multiforme (rarely Stevens-Johnson Syndrome) and an occasional case of exfoliative
dermatitis (including toxic epidermal necrolysis) have been reported. These reactions may be
controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such
reactions occur, the drug should be discontinued, unless the opinion of the physician dictates
otherwise. Serious and occasional fatal hypersensitivity (anaphylactic) reactions can occur with
oral penicillin. (See WARNINGS)
Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated
with ampicilin class antibiotics but the significance of these findings is unkown. Hepatic
dysfunction, inlcuding increases in serum transaminases (AST and/or ALT), serum bilirubin and
or alkaline phosphatase, has been infrequently reported with Augmentin. The histologic findings
on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic-
hepatocellular changes. The hepatic dysfunction , which may be severe, is usually reversible.
On rare occasions, deaths have been reported (less than 1 death reported per estimated 4
million prescriptions worldwide). These have generally been cases associated with serious
underlying diseases or concomitant medications.
Renal: Interstitial nephritis and hematuria have been reported rarely.
Hemic and Lymphatic Systems: 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
hypersensitibity phenomena. A slight thrombocytosis was noted in less than 1% of the patients
treated with Augmentin.
Central Nervous System: Reversible hyperactivity, agitation, anxiety, insomnia, confusion,
behavioral changes, and or dizziness have been reported rarely.
Amoxicillin may be removed from circulation by hemodialysis.
The molecular weight, degree of protein binding and pharmacokinetic profile of clavulanic acid
together with information from a single patient with renal insufficiency all suggest that this
compound may also be removed by hemodialysis.
Dosage:
Pediatric Patients: Based on the amoxicillin component, Augmentin should be dosed as follows:
Neonates and infants aged < 12 weeks (3 months)
Due to incompletely developed renal function affecting elimination of amoxicillin in this age
group, the recommended dose of Augmentin is 30 mg/kg/day divided q12h, based on the
amoxicillin component. Clavulanate elimination is unaltered in this age group. Experience with
the 200 mg/5 mL formulation in this age group is limited and, thus, use of the 125 mg/5 mL oral
suspension is recommended.
“”The q12h regimen is recommended as it is associated with significantly less diarrhea. (See
CLINICAL STUDIES.) However, the q12h formulations (200 mg and 400 mg) contain aspartame
and should not be used by phenylketonurics.
,,Each strength of Augmentin suspension is abailable as a chewable tablet for use by older
children.
***Duration of therapy studied and recommended for acute otitis media is 10 days.
Pediatric Patients weighing 40 kg and more should be dosed according to the following adult
recommendations: The usual adult dose is 1 Augmentin 500 mg tablet every 12 hours or 1
Augmentin 250 mg every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be 1
Augmentin 875 mg tablet every 12 hours or 1 Augmentin 500 mg tablet every 8 hours. Among
adults treated with 875 mg every 12 hours, significantly fewer experienced severe diarrhea or
withdrawals with diarrhea vs. adults treated with 500 mg every 8
hours. For detailed adult dosage recommendation, please see complete prescribing information
for Augmentin Tablets.
Hepatically imparied patients should be dosed with caution and hepatic function monitored at
regular intervals. (See Warnings)
Adults: Adults who have difficulty swallowing may be given the 125 mg/5mL or 250 mg/5 mL
suspension in place of the 500 mg tablet. The 200 mg/5 mL suspension or the 400 mg/5 mL
suspension may be used in place of the 875 mg tablet. See dosage recommendations above for
children weighing 40 kg or more.
The Augmentin 250 mg tablet and the 250 mg chewable tablet do not contain the same amount
of clavulanic acid (as the potassium salt.) The Augmentin 250 mg tablet contains 125 mg of
clavulanic acid, whereas the 250 mg chewable tablet contains 62.5 mg of clavulanic acid.
Therefore, the Augmentin 250 mg tablet and the 250 mg chewable tablet should not be
substituted for each other as they are not interchangeable.
Due to the different amoxicillin to clavulanic acid ratios in the Augmentin 250 mg tablet
(250/125) versus the Augmentin 250 mg chewable tablet (250/62.5) the Augmentin 250 mg tablet
should not be used until the child weighs at least 40 kg or more.
Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows
freely. Add approximately 2/3 of the total amount of water for reconstitution (see table below)
and shake vigorously to suspend powder. Add remainder of the water and again shake
vigorously.
Augmentin 125 mg/5 mL Suspension Amount of Water Bottle Size Required for Reconstitution 75 mL 67 mL 100 mL 90 mL 150 mL 134 mL
Each teaspoonful (5mL)will contain 125 mg amoxicillin and 31.25 mg of clavulanic acid as the
potassium salt.
Augmentin 200 mg/5 mL Suspension Amount of Water Bottle Size Required for suspension 50 mL 47 mL 75 ml 69 mL 100 mL 91 mL
Each teaspoonful (5mL will contain 200 mg amoxicillin and 28.5 mg of clavulanic acid as the
potassium salt.
Augmentin 250 mg/5 mL Suspension Amount of water Bottle Size Required for Reconstitution 75 mL 65 ml 100 mL 87 mL 150 mL 130 mL
Each teaspoon (5mL) will contain 250 mg amoxicillin and 62.5 mg of clavulanic acid as the
potassium salt.
Augmentin 400 mg/5 mL Suspension Amount of Water Bottle Size Required for Suspension 50 mL 44 mL 75 mL 66 mL 100 mL 87 mL
Each teaspoon (5mL) will contain 400 mg amoxicillin and 57.0 mg of clavulanic acid as the
potassium slat.
Note: SHAKE ORAL SUSPENSION WELL BEFORE USING.
Reconstituted suspension must be stored under refrigeration and discarted after 10 days.
Administration: Augmentin may be taken without regard to meals: however, absorption of
clavulanate potassium is enhanced when Augmentin is administered at the start of a meal. To
minimize the potential for gastronatestinal intolerance, Augmentin should be taken at the start of
a meal.
AUGMENTIN 125 MG/5 ML FOR ORAL SUSPENSION: Each 5 mL of reconstituted banana-
flavored suspension contains
125 mg amoxicillin and 31.25 mg clavulanic acid as the potassium salt.
NDC 0029-6085-39…………….75 mL bottle NDC 0029-6085-22………………..150 mL bottle
NDC 0029-6085-23…………….100 mL bottle
AUGMENTIN 200 MG/5 ML FOR ORAL SUSPENSION: Each 5 mL of reconstituted orange-
rasberry-flavored suspension contains 200 mg amoxicillin and 28.5 mg clavulanic acid as the
potassium salt.
NDC0029-6087-29……………..50 mL bottle NDC 0029-6087-51………………..100 mL bottle
NDC 0029-6087-39……………..75 mL bottle
AUGMENTIN 250 MG/5 ML FOR ORAL SUSPENSION: Each 5 mL of reconstituted orange-
flavored suspension contains 250 mg
amoxicillin and 62.5 mg clavulanic acid as the potassium salt.
NDC 0029-6090-39……………..75ml bottle NDC 0029-6090-22……………………150 mL bottle
NDC 0029-6090-23……………..100 ml bottle
AUGMENTIN 400 MG/5 M FOR ORAL SUSPENSION: Each 5 mL of reconstituted orange-
raspberry-flavored suspension contains 400 mg amoxicillin and 57 clavulanic acid as the
potassium salt.
NDC 0029-6092-29…………….50 mL bottle NDC 0029-6092-51……………………100 mL bottle
NDC 0029-6092-39…………….75 mL bottle
AUGMENTIN 125 MG CHEWABLE TABLETS: Each mottled yellow, round, lemon-lime flavored
tablet, debossed with BMP 189,contains 125 mg amoxicillin as the trihydrate and 31.25 mg
clavulanic acid as the potassium salt.
NDC 0029-6073-47…..carton of 30 tablets
AUGMENTIN 200 MG CHEWABLE TABLTS: Each mottled pink, round, biconvex, cherry-
banana-flavored tablet contains 200 mg amoxicillin as the trihydrate and 28.5 mg clavulanic acid
as the potassium salt.
NDC 0029-6071-12…..carton of 20 tablets
AUGMENTIN 250 MG CHEWABLE TABLETS: Each mottled yellow, round lemon-lime flavored
tabled, debossed with BMP 190,
Contains 250 mg amoxicillin as the trihydrate and 62.5 mg clauvulanic acid as the potasium salt.
NDC 0029-6074-47…..carton of 30 tablets
AUGMENTIN 400 MG CHEWABLE TABLETS: Each mottled pink, round, biconvex, cherry-
banana-flavored tablet contains 400 mg amoxicillin as the trihydrate and 57.0 mg clavulanic acid
as the potassium salt.
NDC 0029-6072-12…..carton of 20 tablets
Augmentin is also supplied as:
AUGMENTIN 250 MG TABLETS (250 mg amoxicillin/125 mg clavulanic acid):
NDC 0029-6075-27…………………bottles of 30 NDC 0029-6075-31…100 Unit Dose tablets
AUGMENTIN 500 MG TABLETS (500 mg amoxicillin/125 mg clavulanic acid):
NDC 0029-6086-12………bottles of 20 NDC 0029-6086-21…100 Unit Dose tablets
NDC 0029-6080-27………bottles of 30
AUGMENTIN 875 MG TABLETS (875 mg amoxilcillin/125 mg clavulanic acid):
NDC 0029-6086-12………bottles of 20 NDC 0029-6086-21…100 Unit Dose tablets
Store tablets and dry powder at or below 25C(77F) Dispense in tightly closed, moisture proof
containers. Store reconstituted suspension under refrigeration. Discard unused suspension after
10 days.
In pediatric patients (aged 2 months to 12 years) one U.S canadian clinical trial was conducted
which compared Augmentin 46/6.4 mg/kg/day (divided q12h for 10 days versus Augmentin
40/10mg/kg/day (divided q8h for 10 days in the treatment of acute otitis media. Only the
suspension formulations were used in this trial. A total of 575 patients were enrolled with an
even distribution among the two treatment groups and a comparable number of patients were
evaluable (i.e.84%) per treatment group. Strict otitis media specific criteria were required for
eligibility and strongcorrelation was found at the end of therapy and follow up between these
criteria and physician assessment of clinical reponse. The clinical efficacy rates at the end of therapy visit
(defined as 2-4 days after the completion of therapy) and at the follow up visit d(efined as 22-28
days post-completion of therapy) were comparable for the two treatment froups with the following
cure rates obtained for the evaluable patients: At the end of therapy, 87.2% (n = 265) and 82.3% (n = 260) for 45 mg/kg/day q 12h and 40 mg/kg/day qh8, respectively. At follow-up, 67.1% (n = 249) and 68.7% (n = 243 for 45 mg/kg/day q 12h and 40 mg/kg/day q8h, respectively.
The incidence of diarrheat was significantly lower
in patients in the q12h treatment group compared to patients who received the q8h regimen (14.3% and 34.3%, respectively). In addition, thre number of patients with either severe diarrhea or who were withdrawn with diarrhea was significantly lower in the q 12h treatment group (3.1% and 7.6% for the q12/10 day and q8h/10 day
respectively.) In the q12 treatment group, 3 patients (1.0) were withdrawn with an allergic
reaction while 1 patient (0.3%) in the q8h group was withdrawn for this reason. The number of
patients with a candidal infection of the diaper area was 3.8% and 6.2 for the q 12h and q8h
groups respectively.
It is not known if the finding of a statistically significant reduction in diarrhea with the oral
suspensions dosed q 12h, versus suspensions dosed q8h can be extrapolated to the chewable tablets. The presence of
mannitol in the chewable tablets may contribute to a different diarrhea profile. The q12 oral
suspensions are sweetened with aspartame only.
tDiarrhea was defined as either: (a) three or more watery or four or more loose/watery stools in
one day: OR (b) two watery stools per day or three loose/watery stools per day for two
consecutive days.
1. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial
Susceptibility Tests for Bacteria That Grow Aerobically-Third Edition. Approved Standard
NCCLS Document M7-A3, Vol, 13 No. 25. NCCLS Villanova, PA, Dec 1993.
2. National Committee for Clinical Laboratory Standards. Performance Standard for
Antimicrobial Disk Susceptibility Tests – Fifth Edition. Approved Standard NCCLS Document M-2-A5, Vol 13, No 24. NCCLS Villanova, PA, Dec. 1993.
DATE OF ISSUANCE MAY 1996
© SmithKline Beecham, 1996
SmithKline Beecham Pharmaceuticals
Philadelphia, PA 19101
AG:PL2A
Printed in U.S.A.