WARNINGS
CEFUROXIME AXETIL TABLETS AND POWDER FOR ORAL SUSPENSION
ARE NOT BIOEQUIVALENT AND ARE THEREFORE NOT SUBSTITUTABLE
ON A MG/MG BASIS (SEE CLINICAL PHARMACOLOGY).
BEFORE THERAPY WITH CEFUROXIME AXETIL PRODUCTS IS INSTITUTED,
CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE
PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO
CEFUROXIME AXETIL PRODUCTS, OTHER CEPHALOSPORINS, PENICILLINS,
OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE
PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY
AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED
AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY
OF PENICILLIN ALLERGY. IF A CLINICALLY SIGNIFICANT ALLERGIC
REACTION TO CEFUROXIME AXETIL PRODUCTS OCCURS, DISCONTINUE
THE DRUG AND INSTITUTE APPROPRIATE THERAPY. SERIOUS ACUTE
HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH
EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN,
INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS,
PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.
Pseudomembranous colitis has been reported with
nearly all antibacterial agents, including cefuroxime,
and may range 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 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 effective against Clostridium
difficile.
PRECAUTIONS
General
As with other broad-spectrum antibiotics, prolonged administration
of cefuroxime axetil may result in overgrowth of nonsusceptible
microorganisms. If superinfection occurs during therapy,
appropriate measures should be taken.
Cephalosporins, including cefuroxime axetil, should be
given with caution to patients receiving concurrent treatment
with potent diuretics because these diuretics are suspected
of adversely affecting renal function.
Cefuroxime axetil, as with other broad-spectrum antibiotics,
should be prescribed with caution in individuals with
a history of colitis. The safety and effectiveness of
cefuroxime axetil have not been established in patients
with gastrointestinal malabsorption. Patients with gastrointestinal
malabsorption were excluded from participating in clinical
trials of cefuroxime axetil.
Cephalosporins may be associated with a fall in prothrombin
activity. Those at risk include patients with renal or
hepatic impairment, or poor nutritional state, as well
as patients receiving a protracted course of antimicrobial
therapy, and patients previously stabilized on anticoagulant
therapy. Prothrombin time should be monitored in patients
at risk and exogenous vitamin K administered as indicated.
Information for the Patient/Caregivers (Pediatric)
1. During clinical trials, the tablet was tolerated by
pediatric patients old enough to wswallow the cefuroxime
axetil tablet whole. The crushed tablet has a strong,
persistent, bitter taste and should not be administered
to pediatric patients in this manner. Pediatric patients
who cannot wswallow the tablet whole should receive the
oral suspension.
2. Discontinuation of therapy due to taste and/or problems
of administering this drug occurred in 1.4% of pediatric
patients given the oral suspension. Complaints about taste
(which may impair compliance) occurred in 5% of children.
Drug/Laboratory Test Interactions
A false-positive reaction for glucose in the urine may
occur with copper reduction tests (Benedict's or Fehling's
solution or with Clinitest tablets), but not with enzyme-based
tests for glycosuria (e.g., Clinistix, Tes-Tape). As a
false-negative result may occur in the ferricyanide test,
it is recommended that either the glucose oxidase or hexokinase
method be used to determine blood/plasma glucose levels
in patients receiving cefuroxime axetil. The presence
of cefuroxime does not interfere with the assay of serum
and urine creatinine by the alkaline picrate method.
Carcinogenesis, Mutagenesis, and Impairment of
Fertility
Although lifetime studies in animals have not been performed
to evaluate carcinogenic potential, no mutagenic activity
was found for cefuroxime axetil in a battery of bacterial
mutation tests. Positive results were obtained in an in
vitro chromosome aberration assay, however, negative results
were found in an in vivo micronucleus test at doses up
to 1.5 g/kg. Reproduction studies in rats at doses up
to 1000 mg/kg per day (nine times the recommended maximum
human dose based on mg/m2) have revealed no impairment
of fertility.
Pregnancy, Teratogenic Effects, Pregnancy Category
B
Reproduction studies have been performed in mice at doses
up to 3200 mg/kg per day (14 times the recommended maximum
human dose based on mg/m2) and in rats at doses up to
1000 mg/kg per day (9 times the recommended maximum human
dose based on mg/m2) and have revealed no evidence of
impaired fertility or harm to the fetus due to cefuroxime
axetil. 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
Cefuroxime axetil has not been studied for use during
labor and delivery.
Nursing Mothers
Because cefuroxime is excreted in human milk, consideration
should be given to discontinuing nursing temporarily during
treatment with cefuroxime axetil.
Pediatric Use
The safety and effectiveness of cefuroxime axetil have
been established for pediatric patients aged 3 months
to 12 years for acute bacterial maxillary sinusitis based
upon its approval in adults. Use of cefuroxime axetil
in pediatric patients is supported by pharmacokinetic
and safety data in adults and pediatric patients, and
by clinical and microbiological data from adequate and
well-controlled studies of the treatment of acute bacterial
maxillary sinusitis in adults and of acute otitis media
with effusion in pediatric patients. It is also upported
by post-marketing adverse events surveillance (see CLINICAL
PHARMACOLOGY, CLINICAL STUDIES, INDICATIONS AND USAGE,
ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION.
Geriatric Use
In clinical trials when 12- to 64-year-old patients and
geriatric patients (65 years of age or older) were treated
with usual recommended dosages (i.e., 125 to 500 mg bid,
depending on type of infections), no overall differences
in effectiveness were observed between the two age-groups.
The geriatric patients reported somewhat fewer gastrointestinal
events and less frequent vaginal candidiasis compared with
patients aged 12 to 64 years old; however, no clinically
significant differences were reported between the two age-groups.
Therefore, no adjustment of the usual adult dose is necessary
based on age alone.
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