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 XR, CAREFUL INQUIRY SHOULD BE MADE CONCERNING
PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER
ALLERGENS. IF AN ALLERGIC REACTION OCCURS, AUGMENTIN XR 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
AUGMENTIN XR, 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
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.
AUGMENTIN XR 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).
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 if therapy is for longer than the drug is
approved for administration.
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 spp. or Candida spp.), the drug should be discontinued and/or
appropriate therapy instituted.
Prescribing AUGMENTIN XR 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
Information for Patients
AUGMENTIN XR should be taken every 12 hours with a meal or snack
to reduce the possibility of gastrointestinal upset. If diarrhea develops and is
severe or lasts more than 2 or 3 days, call your doctor.
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.
Patients should be counseled that antibacterial drugs, including
AUGMENTIN XR, should only be used to treat bacterial infections. They do not
treat viral infections (e.g., the common cold). When AUGMENTIN XR 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 AUGMENTIN XR or other antibacterial drugs in the future. Discard
any unused medicine.
Probenecid decreases the renal tubular secretion of amoxicillin.
Concurrent use with AUGMENTIN XR may result in increased and prolonged blood
levels of amoxicillin. Coadministration of probenecid cannot be recommended.
Abnormal prolongation of prothrombin time (increased international normalized
ratio [INR]) has been reported rarely in patients receiving amoxicillin and oral
anticoagulants. Appropriate monitoring should be undertaken when anticoagulants
are prescribed concurrently. Adjustments in the dose of oral anticoagulants may
be necessary to maintain the desired level of anticoagulation.
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. In controlled clinical trials of AUGMENTIN XR, 25
patients received concomitant allopurinol and AUGMENTIN XR. No rashes were
reported in these patients. However, this sample size is too small to allow for
any conclusions to be drawn regarding the risk of rashes with concomitant
AUGMENTIN XR and allopurinol use.
In common with other broad-spectrum antibiotics, AUGMENTIN XR may reduce the
efficacy of oral contraceptives.
Drug/Laboratory Test Interactions
Oral administration of AUGMENTIN XR 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
AUGMENTIN XR, 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, AUGMENTIN XR.
Carcinogenesis, Mutagenesis, Impairment of
Long-term studies in animals have not been performed to evaluate
carcinogenic potential. The mutagenic potential of AUGMENTIN 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. AUGMENTIN at oral doses of up to 1,200 mg/kg/day (1.9 times the
maximum human dose of amoxicillin and 15 times the maximum human dose of
clavulanate 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
Pregnancy Category B. Reproduction studies performed in pregnant
rats and mice given AUGMENTIN at oral doses up to 1,200 mg/kg/day revealed no
evidence of harm to the fetus due to AUGMENTIN. In terms of body surface area,
the doses in rats were 1.6 times the maximum human oral dose of amoxicillin and
13 times the maximum human dose for clavulanate. For mice, these doses were 0.9
and 7.4 times the maximum human oral dose of amoxicillin and clavulanate,
respectively. 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
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 XR 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 AUGMENTIN may be associated with an increased risk of necrotizing
enterocolitis in neonates.
Ampicillin-class antibiotics are excreted in the milk; therefore,
caution should be exercised when AUGMENTIN XR is administered to a nursing
The safety and effectiveness of AUGMENTIN XR have been
established for pediatric patients weighing ≥ 40 kg who are able to swallow
tablets. Use of AUGMENTIN XR in these pediatric patients is supported by
evidence from adequate and well-controlled trials of adults with acute bacterial
sinusitis and community-acquired pneumonia with additional data from a pediatric
A pharmacokinetic study in pediatric patients (7 to 15 years of age and
weighing ≥ 40 kg) was conducted (see CLINICAL PHARMACOLOGY).
The adverse event profile in 44 pediatric patients who received at least one
dose of AUGMENTIN XR was consistent with the established adverse event profile
for the product in adults.
Of the total number of subjects in clinical studies of AUGMENTIN
XR, 18.4% were 65 years or older and 7.2% were 75 years or older. No overall
differences in safety and effectiveness were observed between these subjects and
younger subjects, and other clinical experience has not reported 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.
Each tablet of AUGMENTIN XR contains 29.3 mg (1.27 mEq) of sodium.