WARNINGS
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.
Pseudomembranous colitis has been reported with nearly all
antibacterial agents, including amoxicillin; clavulanate
potassium, 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 administration
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 difficile
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 supplementation and treatment
with an antibacterial drug clinically effective against
Clostridium difficile colitis.
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 one 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.)
PRECAUTIONS
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.
Information for the Patient
Oral Suspension and Chewable Tablets Only: Amoxicillin;
clavulanate potassium 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 amoxicillin; clavulanate
potassium suspension (liquid), use a dosing spoon or medicine
dropper. Be sure to rinse the spoon or dropper after each
use. Bottles of amoxicillin; clavulanate potassium 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
Oral Suspension and Chewable Tablets Only: Each
200 mg amoxicillin; clavulanate potassium 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/5 ml oral suspension contains 7 mg phenylalanine.
The other amoxicillin; clavulanate potassium products do
not contain phenylalanine and can be used by phenylketonurics.
Contact your physician or pharmacist.
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 and therefore
amoxicillin; clavulanate potassium, it is recommended that
glucose tests based on enzymatic glucose oxidase 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 amoxicillin; clavulanate potassium.
Carcinogenesis, Mutagenesis, and Impairment of
Fertility
Long-term studies in animals have not been performed
to evaluate carcinogenic potential.
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 mouse
lymphoma assay where weak activity was found at very high,
cytotoxic concentrations.
Impairment of Fertility: Amoxicillin;
clavulanate potassium 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:clavulanate.
Pregnancy, Teratogenic Effects, Pregnancy Category
B
Reproduction studies performed in pregnant rats
and mice given amoxicillin; clavulanate potassium 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 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.
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.
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.
Pediatric Use
Oral Suspension and Chewable Tablets: Because of
incompletely developed renal function in neonates and young
infants, the elimination of amoxicillin may be delayed.
Dosing of amoxicillin; clavulanate potassium should be modified
in pediatric patients younger than 12 weeks (3 months).
(See DOSAGE AND ADMINISTRATION, Pediatric.)
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