SIDE EFFECTS
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. 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 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.
Oral Solution and Chewable Tablets: In
pediatric patients (aged 2 months to 12 years), one U.S./Canadian
clinical trial was conducted which compared amoxicillin;
clavulanate potassium 45/6.4 mg/kg/day (divided q12h) for
10 days versus amoxicillin; clavulanate potassium 40/10
mg/kg/day (divided q8h) for 10 days in the 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 above. 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, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous
colitis. Onset of pseudomembranous colitis symptoms may
occur during or after antibiotic treatment. (See WARNINGS.)
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) 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 ampicillin
class antibiotics but the significance of these findings
is unknown. Hepatic dysfunction, including 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
one 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, 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.
Central Nervous System: Agitation, anxiety,
behavioral changes, confusion, convulsions, dizziness, insomnia,
and reversible hyperactivity have been reported rarely.
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. Co-administration 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.
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