Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3582
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AMOXICILLIN AND CLAVULANATE POTASSIUM (Tablet)
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dailymed-instance:dosage |
Since both the 250-mg
and 500-mg tablets of amoxicillin/clavulanate potassium contain the
same amount of clavulanic acid (125 mg, as the potassium salt),
two amoxicillin/clavulanate potassium 250-mg tablets are not equivalent
to one 500-mg amoxicillin/clavulanate potassium tablet. Therefore
two 250-mg amoxicillin/clavulanate potassium tablets should not be
substituted for one 500-mg amoxicillin/clavulanatepotassium tablet.<br/>Dosage:<br/>Adults: The usual adult dose is one 500-mg tablet of amoxicillin/clavulanate
potassium every 12 hours or one 250-mg tablet of amoxicillin/clavulanate
potassium every 8 hours. For more severe infections and infections
of the respiratory tract, the dose should be one 875-mg tablet of
amoxicillin/clavulanate potassium every 12 hours or one 500-mg
tablet of amoxicillin/clavulanate potassium every 8 hours. 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<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. Hepatically impaired patients should be dosed with caution
and hepatic function monitored at regular intervals. (See WARNINGS.)<br/>Pediatric Patients: Pediatric patients weighing 40 kg or more should be dosed according to the adult
recommendations. Due
to the different amoxicillin to clavulanic acid ratios in the amoxicillin/clavulanate
potassium 250-mg tablet (250/125) versus the amoxicillin/clavulanate
potassium 250-mg chewable tablet (250/62.5), the amoxicillin/clavulanate
potassium 250-mg tablet should not be used until the pediatric patient
weighs at least 40 kg or more.<br/>Administration: Amoxicillin/clavulanate potassium may be taken without
regard to meals; however, absorption of clavulanate potassium is enhanced
when amoxicillin/clavulanate potassium is administered at the start
of a meal. To minimize the potential for gastrointestinal intolerance,
amoxicillin/clavulanate potassium should be taken at the start of
a meal.
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dailymed-instance:descripti... |
Amoxicillin/clavulanate potassium is an oral antibacterial
combination consisting of the semisynthetic antibiotic amoxicillin
and the��-lactamase inhibitor, clavulanate potassium (the potassium
salt of clavulanic acid). Amoxicillin is an analog of ampicillin,
derived from the basic penicillin nucleus, 6-aminopenicillanic acid.
The amoxicillin molecular formula is CHNOS���3HO, and the molecular weight
is 419.46. Chemically, amoxicillin 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 and may be represented structurally as: Clavulanic acid is produced
by the fermentation of Streptomyces clavuligerus. It is a��-lactam structurally related to the penicillins
and possesses the ability to inactivate a wide variety of��-lactamases
by blocking the active sites of these enzymes. Clavulanic acid is
particularly active against the clinically important plasmid-mediated��-lactamases frequently responsible for transferred drug resistance
to penicillins and cephalosporins. The clavulanate potassium molecular
formula is CHKNOand 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:<br/>Inactive Ingredients: Colloidal silicon dioxide, hypromellose, magnesium
stearate, microcrystalline cellulose, polyethylene glycol, sodium
starch glycolate, and titanium dioxide. Each
tablet of amoxicillin/clavulanate potassium contains 0.63 mEq
potassium.
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dailymed-instance:clinicalP... |
Amoxicillin and clavulanate potassium are well absorbed
from the gastrointestinal tract after oral administration of amoxicillin/clavulanate
potassium. Dosing in the fasted or fed state has minimal effect on
the pharmacokinetics of amoxicillin. While amoxicillin/clavulanate
potassium can be given without regard to meals, absorption of clavulanate
potassium when taken with food is greater relative to the fasted state.
In 1 study, the relative bioavailability of clavulanate was reduced
when amoxicillin/clavulanate potassium was dosed at 30 and 150 minutes
after the start of a high-fat breakfast. The safety and efficacy of
amoxicillin/clavulanate potassium have been established in clinical
trials where amoxicillin/clavulanate potassium was taken without regard
to meals. Meanamoxicillin and
clavulanate potassium pharmacokinetic parameters are shown in the
table below: Amoxicillin serum concentrations achieved with
amoxicillin/clavulanate potassium 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 amoxicillin/clavulanate
potassium is 1.3 hours and that of clavulanic acid is 1.0 hour. 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 a single 250-mg
or 500-mg tablet of amoxicillin/clavulanate potassium. Concurrent administration of probenecid delays amoxicillin
excretion but does not delay renal excretion of clavulanic acid. Neither component in amoxicillin/clavulanate potassium
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 clavulanic acid to
animals suggest that this compound, like amoxicillin, is well distributed
in body tissues.<br/>Microbiology: Amoxicillin is a semisynthetic antibiotic with a
broad spectrum of bactericidal activity against many gram-positive
and gram-negative microorganisms. Amoxicillin is, however, susceptible
to degradation by��-lactamases, and therefore, the spectrum
of activity does not include organisms which produce these enzymes.
Clavulanic acid is a��-lactam, structurally related to the penicillins,
which possesses the ability to inactivate a wide range of��-lactamase
enzymes commonly found in microorganisms resistant to penicillins
and cephalosporins. In particular, it has good activity against the
clinically important plasmid-mediated��-lactamases frequently
responsible for transferred drug resistance. The formulation of amoxicillin and clavulanic acid in amoxicillin/clavulanate
potassium protects amoxicillin from degradation by��-lactamase
enzymes and effectively extends the antibiotic spectrum of amoxicillin
to include many bacteria normally resistant to amoxicillin and other��-lactam antibiotics. Thus, amoxicillin/clavulanate potassium
possesses the properties of a broad-spectrum antibiotic and a��-lactamase
inhibitor. Amoxicillin/clavulanic acid has
been shown to be active against most strains of the following microorganisms,
both in vitro and in clinical infections as described in INDICATIONS
AND USAGE.<br/>Gram-Positive Aerobes: Staphylococcus aureus (��-lactamase and non�����-lactamase���producing) Staphylococci
which are resistant to methicillin/oxacillin must be considered resistant
to amoxicillin/clavulanic acid.<br/>Gram-Negative Aerobes: Enterobacter species (Although most strains of Enterobacter species are resistant in vitro, clinical efficacy has been demonstrated
with amoxicillin/clavulanate potassium in urinary tract infections
caused by these organisms.) Escherichia coli (��-lactamase
and non�����-lactamase���producing) Haemophilus influenzae (��-lactamase
and non�����-lactamase���producing) Klebsiella species (All known
strains are��-lactamase���producing.) Moraxella catarrhalis (��-lactamase
and non�����-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 2 mcg/mL or less against most (���90%)
strains of Streptococcus pneumoniae; MICs of 0.06 mcg/mL or less against most
(���90%) strains of Neisseria gonorrhoeae; MICs of 4 mcg/mL or less against most (���90%) strains
of staphylococci and anaerobic bacteria; and MICs of 8 mcg/mL
or less against most (���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 S. pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate
susceptibility to ampicillin or penicillin are fully susceptible to
amoxicillin.<br/>Gram-Positive Aerobes: Enterococcus faecalis Staphylococcus epidermidis (��-lactamase and non�����-lactamase���producing) Staphylococcus saprophyticus (��-lactamase and non�����-lactamase���producing) Streptococcus pneumoniae Streptococcus pyogenes viridans group Streptococcus<br/>Gram-Negative Aerobes: Eikenella corrodens (��-lactamase and non�����-lactamase���producing) Neisseria gonorrhoeae(��-lactamase and non�����-lactamase���producing) Proteus mirabilis(��-lactamase and non�����-lactamase���producing)<br/>Anaerobic Bacteria: Bacteroides species, including Bacteroides fragilis (��-lactamase and non�����-lactamase���producing) Fusobacterium species
(��-lactamase and non-��-lactamase���producing) Peptostreptococcus species Adequate
and well-controlled clinical trials have established the effectiveness
of amoxicillin alone in treating certain clinical infections due to
these organisms. These are
non-��-lactamase���producing organisms and, therefore, are
susceptible to amoxicillin alone.<br/>Susceptibility Testing:<br/>Dilution Techniques: Quantitative methods are used to determine antimicrobial
MICs. These MICs provide estimates of the susceptibility of bacteria
to antimicrobial compounds. The MICs should be determined using a
standardized 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: For Staphylococcusand Haemophilus species: For S. pneumoniae from non-meningitis sources: Isolates should be tested
using amoxicillin/clavulanic acid and the following criteria should
be used: Note: These interpretive criteria are based on
the recommended doses for respiratory tract infections. 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 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 amoxicillin/clavulanate potassium powder should
provide the following MIC values: Microorganism MIC Range (mcg/mL) E.
coli ATCC 25922 2 to 8 E. coli ATCC 35218 4 to 16 E. faecalis ATCC
29212 0.25 to 1.0 H. influenzae ATCC 49247 2 to 16 S. aureus ATCC 29213 0.12
to 0.5 S. pneumoniae 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.<br/>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 procedurerequires the use of standardized inoculum concentrations.
This procedure uses paper disks impregnated with 30 mcg of amoxicillin/clavulanate
potassium (20 mcg amoxicillin plus 10 mcg 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-mcg
amoxicillin/clavulanate potassium (20-mcg amoxicillin plus 10-mcg
clavulanate potassium) disk should be interpreted according to the
following criteria: RECOMMENDED RANGES FOR AMOXICILLIN/CLAVULANIC
ACID SUSCEPTIBILITY TESTING For Staphylococcusspecies and
H. influenzae: For other organisms except S. pneumoniaeand N. gonorrhoeae: 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-mcg amoxicillin/clavulanate potassium
(20-mcg amoxicillin plus 10-mcg clavulanate potassium) disk should
provide the following zone diameters in these laboratory quality control
strains: Microorganism
Zone Diameter (mm) E. coli ATCC 25922 19 to 25 E. coli ATCC 35218
18 to 22 S. aureus ATCC 25923 28 to 36
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dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
Amoxicillin/clavulanate potassium is contraindicated
in patients with a history of allergic reactions to any penicillin.
It is also contraindicated in patients with a previous history of
cholestatic jaundice/hepatic dysfunction associated with amoxicillin/clavulanate
potassium.
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dailymed-instance:supply |
500-mg Tablets: Each white, oval, film-coated tablet, debossed with PL 500 on one
side and blank on the other side, contains 500 mg amoxicillin as the trihydrate and 125 mg clavulanic acid as the potassium
salt. NDC 49884-298-07 bottles of 20 NDC 49884-298-12 Unit Dose carton of 100 tablets 875-mg Tablets: Each
scored, white, capsule-shaped tablet, debossed with PL 875 on one
side and scored on the other side, contains 875 mg amoxicillin as the trihydrate and 125 mg clavulanic acid as the potassium
salt. NDC 49884-299-07 bottles of 20 NDC 49884-299-12 Unit Dose carton of 100 tablets Store tablets at or below 25��C (77��F). Dispense
in original container.
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dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... |
dailymed-ingredient:colloidal_silicon_dioxide,
dailymed-ingredient:hypromellose,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:potassium,
dailymed-ingredient:sodium_starch_glycolate,
dailymed-ingredient:titanium_dioxide
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dailymed-instance:precautio... |
General: While amoxicillin/clavulanate potassium possesses
the characteristic low toxicity of the penicillin group of antibiotics,
periodic assessment of organ system functions, including renal, hepatic,
and hematopoietic 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. Prescribing amoxicillin/clavulanate potassium 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.<br/>Drug Interactions: Probenecid decreases the renal tubular secretion
of amoxicillin. Concurrent use with amoxicillin/clavulanate potassium
may result in increased and prolonged blood levels of amoxicillin.
Coadministration of probenecid cannot be recommended. The concurrent administration of allopurinol and ampicillin
increases substantially the incidence of rashes in 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 present in these patients. There
are no data with amoxicillin/clavulanate potassium and allopurinol
administered concurrently. In common with other
broad-spectrum antibiotics, amoxicillin/clavulanate potassium may
reduce the efficacy of oral contraceptives.<br/>Drug/Laboratory Test Interactions: Oral administration of amoxicillin/clavulanate potassium
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 Solution.
Since this effect may also occur with amoxicillin andtherefore amoxicillin/clavulanate
potassium, 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
and therefore amoxicillin/clavulanate potassium.<br/>Information for Patients: Patients should be counseled that antibacterial
drugs including amoxicillin/clavulanate potassium, should only be
used to treat bacterial infections. They do not treat viral infections
(e.g., the common cold). When amoxicillin/clavulanate potassium 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/clavulanate potassium 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 two or more months after having taken the last
dose of the antibiotic. If this occurs, patients should contact their
physician as soon as possible.<br/>Carcinogenesis, Mutagenesis, Impairment
of Fertility: Long-term studies in animals have not been performed
to evaluate carcinogenic potential.<br/>Mutagenesis: The mutagenic potential of amoxicillin/clavulanate
potassium was investigated in vitro with an Ames test, a human lymphocyte
cytogenetic assay, a yeast test and a mouse lymphoma forward mutation
assay, and in vivo with mouse micronucleus tests and a dominant lethal
test. All were negative apart from the in vitro mouselymphoma assay
where weak activity was found at very high, cytotoxic concentrations.<br/>Impairment of Fertility: Amoxicillin/clavulanate potassium at oral doses
of up to 1,200 mg/kg/day (5.7 times the maximum human dose,
1,480 mg/m/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:clavulanate.<br/>Teratogenic Effects: Pregnancy (Category B). Reproduction studies performed
in pregnant rats and mice given amoxicillin/clavulanate potassium
at oral dosages up to 1,200 mg/kg/day, equivalent to 7,200 and
4,080 mg/m/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 amoxicillin/clavulanate potassium.
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.<br/>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 amoxicillin/clavulanate
potassium 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. In a single study
in women with premature rupture of fetal membranes, it was reported
that prophylactic treatment with amoxicillin/clavulanate potassium
may be associated with an increased risk of necrotizing enterocolitis
in neonates.<br/>Nursing Mothers: Ampicillin-class antibiotics are excreted in the
milk; therefore, caution should be exercised when amoxicillin/clavulanate
potassium is administered to a nursing woman.<br/>Geriatric Use: An analysis of clinical studies of AUGMENTIN was
conducted to determine whether subjects aged 65 and over respond differently
from younger subjects. Of the 3,119 patients in this analysis, 68%
were<65 years old, 32% were���65 years old and 14% were���75 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 dose-dependent
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, it may be useful to monitor renal function.
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dailymed-instance:overdosag... |
Following overdosage, patients have experienced primarily gastrointestinal symptoms including stomach
and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or
drowsiness have also been observed in a small number of patients. In the case of overdosage, discontinue amoxicillin/clavulanate
potassium, 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 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. 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 both amoxicillin and clavulanate. Both amoxicillin and clavulanate
are removed from the circulation by hemodialysis. (See DOSAGE AND
ADMINISTRATION for recommended dosing for patients with impaired renal
function.)
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dailymed-instance:genericMe... |
amoxicillin and clavulanate potassium
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dailymed-instance:fullName |
AMOXICILLIN AND CLAVULANATE POTASSIUM (Tablet)
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dailymed-instance:adverseRe... |
Amoxicillin/clavulanate potassium is 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. The most frequently
reported adverse effects were diarrhea/loose stools (9%), nausea (3%),
skin rashes 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 frequently
reported reactions include: Abdominal discomfort, flatulence, and
headache. The following adverse reactions
have been reported for ampicillin-class antibiotics:<br/>Gastrointestinal: Diarrhea, nausea, vomiting, indigestion, gastritis,
stomatitis, glossitis, black���hairy���tongue, mucocutaneous
candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis.
Onset of pseudomembranous colitis symptoms may occur during or after
antibiotic treatment. (See WARNINGS.)<br/>Hypersensitivity Reactions: Skin rashes, pruritus, urticaria, angioedema, serum
sickness���like reactions (urticaria or skin rash accompanied
by arthritis, arthralgia, myalgia, and frequently fever),
erythema multiforme (rarely Stevens-Johnson syndrome), acute generalized
exanthematous pustulosis, hypersensitivity vasculitis, 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.)<br/>Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT)
has been noted in patients treated with ampicillin-class antibiotics,
but the significance of these findings is unknown. Hepatic dysfunction,
including hepatitis and cholestatic jaundice, [see CONTRAINDICATIONS], increases in serum transaminases (AST and/or ALT), serum bilirubin
and/or alkaline phosphatase, has been infrequently reported with amoxicillin/clavulanate
potassium. It has been reported more commonly in the elderly, in males,
or in patients on prolonged treatment. The histologic findings on
liver biopsy have consisted of predominantly cholestatic, hepatocellular,
or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms
of hepatic dysfunction may occur during or several weeks after therapy
has been discontinued. 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.<br/>Renal: Interstitial nephritis and hematuria have been reported
rarely. Crystalluria has also been reported (see OVERDOSAGE).<br/>Hemic and Lymphatic System: 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. A slight thrombocytosis was noted
in less than 1% of the patients treated with amoxicillin/clavulanate
potassium. There have been reports of increased prothrombin time in
patients receiving amoxicillin/clavulanate potassium and anticoagulant
therapy concomitantly.<br/>Central Nervous System: Agitation, anxiety, behavioral changes, confusion,
convulsions, dizziness, insomnia, and reversible hyperactivity have
been reported rarely.<br/>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.
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dailymed-instance:warning |
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 AMOXICILLIN/CLAVULANATE POTASSIUM,
CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY
REACTIONS TO PENICILLINS, CEPHALOSPORINS OR OTHER ALLERGENS. IF AN
ALLERGIC REACTION OCCURS, AMOXICILLIN/CLAVULANATE POTASSIUM SHOULD
BE DISCONTINUED AND THE 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/clavulanate potassium, 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. Amoxicillin/clavulanate potassium should be used with
caution in patients with evidence of hepatic dysfunction. Hepatic
toxicity associated with the use of amoxicillin/clavulanate potassium
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.)
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Amoxicillin/clavulanate potassium 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��-lactamase���producing strains of H. influenzae and M. (Branhamella) catarrhalis. Otitis Media���caused
by��-lactamase���producing strains of H. influenzae and M. catarrhalis. Sinusitis���caused by��-lactamase���producing
strains of H. influenzae and M. catarrhalis. Skin and Skin Structure Infections���caused by��-lactamase���producing strains of S. aureus, E. coli and Klebsiella spp. Urinary Tract
Infections���caused by��-lactamase���producing
strains of E. coli, Klebsiella spp., and Enterobacter spp. While amoxicillin/clavulanate potassium is indicated only for the
conditions listed above, infections caused by ampicillin-susceptible
organisms are also amenable to treatment with amoxicillin/clavulanate
potassium due to its amoxicillin content. Therefore, mixed infections
caused by ampicillin-susceptible organisms and��-lactamase���producing
organisms susceptible to amoxicillin/clavulanate potassium should
not require the addition of another antibiotic. Because amoxicillin
has greater in vitro activity against S. 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 amoxicillin/clavulanate potassium.
(See Microbiology.) To reduce the development
of drug-resistant bacteria and maintain the effectiveness of amoxicillin/clavulanate
potassium and other antibacterial drugs, amoxicillin/clavulanate potassium
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. Bacteriological
studies, to determine the causative organisms and their susceptibility
to amoxicillin/clavulanate potassium, should be performed together
with any indicated surgical procedures.
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AMOXICILLIN AND CLAVULANATE POTASSIUM
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