Rx OnlyTo reduce the development of
drug-resistant bacteria and maintain the effectiveness of cefuroxime axetil and
other antibacterial drugs, cefuroxime axetil should be used only to treat or
prevent infections that are proven or strongly suspected to be caused by
bacteria.
Description
Cefuroxime axetil tablets contain cefuroxime as cefuroxime axetil. Cefuroxime
axetil is a semisynthetic, broad-spectrum cephalosporin antibiotic for oral
administration. Chemically, cefuroxime axetil, the 1-(acetyloxy) ethyl
ester of cefuroxime, is (RS )-1-hydroxyethyl (6R,7R)-7-[2-(2-furyl)glyoxyl-amido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylate,
72-(Z)-(O-methyl-oxime), 1-acetate 3-carbamate. Its molecular
formula is C20H22N4O10S, and it has a molecular weight of
510.48. Cefuroxime axetil is in the amorphous form and has the following
structural formula:
Cefuroxime axetil tablets are uncoated and contain the equivalent of 125, 250 or
500 mg of cefuroxime as cefuroxime axetil. Cefuroxime axetil tablets contain the
inactive ingredients colloidal silicon dioxide, croscarmellose sodium,
hydrogenated vegetable oil, microcrystalline cellulose and sodium lauryl
sulfate.
Clinical Pharmacology
Absorption and Metabolism: After oral administration,
cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly
hydrolyzed by nonspecific esterases in the intestinal mucosa and blood to
cefuroxime. Cefuroxime is subsequently distributed throughout the extracellular
fluids. The axetil moiety is metabolized to acetaldehyde and acetic
acid.
Pharmacokinetics: Approximately 50%of serum
cefuroxime is bound to protein. Serum pharmacokinetic parameters for cefuroxime
axetil tablets are shown in Table 1.
Table 1. Postprandial Pharmacokinetics of Cefuroxime Administered
as Cefuroxime Axetil Tablets to Adults*
Dose†
(CefuroximeEquivalent)
Peak PlasmaConcentration(mcg/mL)
Time of PeakPlasma
Concentration (hr)
Mean EliminationHalf-Life (hr)
AUC(mcg-hr mL)
125 mg
2.1
2.2
1.2
6.7
250 mg
4.1
2.5
1.2
12.9
500 mg
7
3
1.2
27.4
1,000 mg
13.6
2.5
1.3
50
* Mean values of 12 healthy adult volunteers.
† Drug administered immediately after a meal.
Comparative Pharmacokinetic Properties: Cefuroxime axetil for oral
suspension was not bioequivalent to cefuroxime axetil tablets when tested in
healthy adults. The tablet and powder for oral suspension formulations are NOT
substitutable on a milligram-per-milligram basis. The area under the
curve for the suspension averaged 91%of that for the tablet, and the peak plasma
concentration for the suspension averaged 71%of the peak plasma concentration of
the tablets. Therefore, the safety and effectiveness of both the tablet and oral
suspension formulations had to be established in separate clinical
trials.
Food Effect on Pharmacokinetics:
Absorption of the tablet is greater when taken after food (absolute
bioavailability of cefuroxime axetil tablets increases from 37%to 52%). Despite
this difference in absorption, the clinical and bacteriologic responses of
patients were independent of food intake at the time of tablet administration in
2 studies where this was assessed.
Renal Excretion:
Cefuroxime is excreted unchanged in the urine; in adults, approximately
50%of the administered dose is recovered in the urine within 12 hours. The
pharmacokinetics of cefuroxime in the urine of pediatric patients have not been
studied at this time. Until further data are available, the renal
pharmacokinetic properties of cefuroxime axetil established in adults should not
be extrapolated to pediatric patients. Because cefuroxime is renally
excreted, the serum half-life is prolonged in patients with reduced renal
function. In a study of 20 elderly patients (mean age = 83.9 years) having a
mean creatinine clearance of 34.9 mL/min, the mean serum elimination half-life
was 3.5 hours. Despite the lower elimination of cefuroxime in geriatric
patients, dosage adjustment based on age is not necessary (see PRECAUTIONS: Geriatric
Use
).
Microbiology: The in vivo bactericidal activity of cefuroxime axetil is due
to cefuroxime’s binding to essential target proteins and the resultant
inhibition of cell-wall synthesis. Cefuroxime has bactericidal activity
against a wide range of common pathogens, including many
beta-lactamase–producing strains. Cefuroxime is stable to many bacterial
beta-lactamases, especially plasmid-mediated enzymes that are commonly found in
enterobacteriaceae. Cefuroxime has been demonstrated to be active
against most strains of the following microorganisms both in
vitro and in clinical infections as described in the INDICATIONS AND
USAGE section (see INDICATIONS AND
USAGE section).
Aerobic
Gram-Positive Microorganisms:
Staphylococcus aureus (including beta-lactamase–producing
strains)
Streptococcus pneumoniaeStreptococcus
pyogenes
Aerobic
Gram-Negative Microorganisms:
Escherichia coli
Haemophilus
influenzae (including beta-lactamase–producing strains)
Haemophilus parainfluenzae
Klebsiella pneumoniae
Moraxella
catarrhalis (including beta-lactamase–producing strains)
Neisseria gonorrhoeae (including beta-lactamase–producing
strains)
Spirochetes:
Borrelia burgdorferi
Cefuroxime has
been shown to be active in vitro against most strains
of the following microorganisms; however, the clinical significance of these
findings is unknown. Cefuroxime exhibits in
vitro minimum inhibitory concentrations (MICs) of 4 mcg/mL or less
(systemic susceptible breakpoint) against most (≥90%) strains of the following
microorganisms; however, the safety and effectiveness of cefuroxime in treating
clinical infections due to these microorganisms have not been established in
adequate and well-controlled trials.
Aerobic Gram-Positive Microorganisms:
Staphylococcus epidermidis
Staphylococcus saprophyticus
Streptococcus agalactiae
NOTE: Listeria monocytogenes and certain strains of enterococci,
e.g., Enterococcus faecalis (formerly Streptococcus faecalis), are resistant to cefuroxime.
Methicillin-resistant staphylococci are resistant to cefuroxime.
Aerobic Gram-Negative
Microorganisms:
Morganella
morganii
Proteus inconstans
Proteus mirabilis
Providencia
rettgeri
NOTE: Pseudomonas spp.,
Campylobacter spp., Acinetobacter
calcoaceticus, Legionella spp., and most
strains of Serratia spp. and Proteus vulgaris are resistant to most first- and
second-generation cephalosporins. Some strains of Morganella
morganii, Enterobacter cloacae, and Citrobacter spp. have been shown by in
vitro tests to be resistant to cefuroxime and other
cephalosporins.
Anaerobic
Microorganisms:
Peptococcus
niger
NOTE: Most strains of Clostridium
difficile and Bacteroides fragilis are
resistant to cefuroxime.
Susceptibility Tests: Dilution Techniques:
Quantitative methods that are
used to determine MICs provide reproducible estimates of the susceptibility of
bacteria to antimicrobial compounds. One such standardized procedure uses a
standardized dilution method1 (broth, agar, or
microdilution) or equivalent with cefuroxime powder. The MIC values obtained
should be interpreted according to the following criteria:
MIC
(mcg/mL)
Interpretation
≤4
(S) Susceptible
8-16
(I) Intermediate
≥32
(R)
Resistant
A report of “Susceptible” indicates
that the pathogen, if in the blood, is likely to be inhibited by usually
achievable concentrations of the antimicrobial compound in blood. A report of
“Intermediate” indicates that inhibitory concentrations of the antibiotic may be
achieved if high dosage is used or if the infection is confined to tissues or
fluids in which high antibiotic concentrations are attained. This category also
provides a buffer zone that prevents small, uncontrolled technical factors from
causing major discrepancies in interpretation. A report of “Resistant” indicates
that usually achievable concentrations of the antimicrobial compound in the
blood are unlikely to be inhibitory and that other therapy should be
selected.
Standardized susceptibility test procedures require the use of
laboratory control microorganisms. Standard cefuroxime powder should give the
following MIC values:
Microorganism
MIC
(mcg/mL)
Escherichia coli ATCC 25922
2-8
Staphylococcus aureus ATCC 29213
0.5-2
Diffusion Techniques:
Quantitative methods that
require measurement of zone diameters provide estimates of the susceptibility of
bacteria to antimicrobial compounds. One such standardized procedure2 that has been recommended (for use with disks) to test the
susceptibility of microorganisms to cefuroxime uses the 30 mcg cefuroxime disk.
Interpretation involves correlation of the diameter obtained in the disk test
with the MIC for cefuroxime.
Reports from the laboratory providing
results of the standard single-disk susceptibility test with a 30 mcg cefuroxime
disk should be interpreted according to the following criteria:
Zone
Diameter (mm)
Interpretation
≥23
(S) Susceptible
15-22
(I) Intermediate
≤14
(R)
Resistant
Interpretation should be as stated
above for results using dilution techniques.
As with standard dilution
techniques, diffusion methods require the use of laboratory control
microorganisms. The 30 mcg cefuroxime disk provides the following zone diameters
in these laboratory test quality control strains:
Microorganism
Zone Diameter
(mm)
Escherichia coli ATCC 25922
20-26
Staphylococcus aureus ATCC 25923
27-35
Indications And Usage
To reduce the development of drug-resistant bacteria and maintain the
effectiveness of cefuroxime axetil and other antibacterial drugs, cefuroxime
axetil 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.
NOTE: CEFUROXIME AXETIL TABLETS AND
CEFUROXIME AXETIL FOR ORAL SUSPENSION ARE NOT BIOEQUIVALENT AND ARE NOT
SUBSTITUTABLE ON A MILLIGRAM-PER-MILLIGRAM BASIS (SEE CLINICAL PHARMACOLOGY).Cefuroxime Axetil Tablets: Cefuroxime axetil tablets are
indicated for the treatment of patients with mild to moderate infections caused
by susceptible strains of the designated microorganisms in the conditions uled
below:
1. Pharyngitis/Tonsillitis caused by Streptococcus pyogenes.
NOTE:
The usual drug of choice in the treatment and prevention of streptococcal
infections, including the prophylaxis of rheumatic fever, is penicillin given by
the intramuscular route. Cefuroxime axetil tablets are generally effective in
the eradication of streptococci from the nasopharynx; however, substantial data
establishing the efficacy of cefuroxime in the subsequent prevention of
rheumatic fever are not available. Please also note that in all clinical trials,
all isolates had to be sensitive to both penicillin and cefuroxime. There are no
data from adequate and well-controlled trials to demonstrate the effectiveness
of cefuroxime in the treatment of penicillin-resistant strains of Streptococcus pyogenes.
2. Acute Bacterial Otitis Media
caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase–producing
strains), Moraxella catarrhalis (including
beta-lactamase–producing strains), or Streptococcus
pyogenes.
3. Acute
Bacterial Maxillary Sinusitis caused by Streptococcus
pneumoniae or Haemophilus influenzae
(non-beta-lactamase–producing strains only). (See CLINICAL STUDIES section.)
NOTE: In view of the insufficient numbers of isolates of
beta-lactamase–producing strains of Haemophilus influenzae
and Moraxella catarrhalis that were obtained
from clinical trials with cefuroxime axetil tablets for patients with acute
bacterial maxillary sinusitis, it was not possible to adequately evaluate the
effectiveness of cefuroxime axetil tablets for sinus infections known,
suspected, or considered potentially to be caused by beta-lactamase–producing
Haemophilus influenzae or Moraxella catarrhalis.
4. Acute Bacterial Exacerbations of
Chronic Bronchitis and Secondary Bacterial Infections of Acute Bronchitis
caused by Streptococcus pneumoniae, Haemophilus influenzae (beta-lactamase negative strains),
or Haemophilus parainfluenzae (beta-lactamase
negative strains). (See DOSAGE AND
ADMINISTRATION section and CLINICAL STUDIES section.)
5. Uncomplicated Skin and Skin-Structure
Infections caused by Staphylococcus aureus
(including beta-lactamase–producing strains) or Streptococcus pyogenes.
6. Uncomplicated Urinary Tract Infections
caused by Escherichia coli or Klebsiella pneumoniae.
7. Uncomplicated Gonorrhea,
urethral and endocervical, caused by penicillinase-producing and
non-penicillinase–producing strains of Neisseria gonorrhoeae
and uncomplicated gonorrhea, rectal, in females, caused by
non-penicillinase–producing strains of Neisseria
gonorrhoeae.
8. Early Lyme Disease (erythema
migrans) caused by Borrelia burgdorferi.
Contraindications
Cefuroxime axetil products are contraindicated in patients with known allergy to
the cephalosporin group of antibiotics.
Warnings
CEFUROXIME AXETIL TABLETS AND CEFUROXIME AXETIL FOR ORAL
SUSPENSION ARE NOT BIOEQUIVALENT AND ARE THEREFORE NOT SUBSTITUTABLE ON A
MILLIGRAM-PER-MILLIGRAM 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.Clostridium
difficile associated diarrhea (CDAD) has been reported with use of
nearly all antibacterial agents, including cefuroxime, 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.
Precautions
GeneralAs 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. Prescribing
cefuroxime axetil 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. 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.Information for Patients/Caregivers
(Pediatric)1. During clinical trials, the tablet was tolerated by
pediatric patients old enough to swallow 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
swallow the tablet whole should receive the oral suspension.
2. Patients
should be counseled that antibacterial drugs, including cefuroxime axetil,
should only be used to treat bacterial infections. They do not treat viral
infections (e.g., the common cold). When cefuroxime axetil 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 cefuroxime axetil or other antibacterial drugs in the future.Drug/Laboratory Test InteractionsA
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®). 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.Drug/Drug InteractionsConcomitant
administration of probenecid with cefuroxime axetil tablets increases the area
under the serum concentration versus time curve by 50%. The peak serum
cefuroxime concentration after a 1.5 g single dose is greater when taken with 1
g of probenecid (mean = 14.8 mcg/mL) than without probenecid (mean = 12.2
mcg/mL). Drugs that reduce gastric acidity may result in a lower
bioavailability of cefuroxime axetil compared with that of fasting state and
tend to cancel the effect of postprandial absorption. In common with
other antibiotics, cefuroxime axetil may affect the gut flora, leading to lower
estrogen reabsorption and reduced efficacy of combined oral
estrogen/progesterone contraceptives.Carcinogenesis,Mutagenesis,Impairment Of
FertilityAlthough 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 1,000 mg/kg/day (9 times the recommended maximum human dose
based on mg/m2) have revealed no impairment of
fertility.PregnancyTeratogenic EffectsPregnancy Category B.
Reproduction studies have been performed in mice at doses up to 3,200 mg/kg/day
(14 times the recommended maximum human dose based on mg/m2) and in rats at doses up to 1,000 mg/kg/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 DeliveryCefuroxime axetil has not
been studied for use during labor and delivery.Nursing MothersBecause cefuroxime is
excreted in human milk, consideration should be given to discontinuing nursing
temporarily during treatment with cefuroxime axetil.Pediatric UseThe 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 supported by
postmarketing adverse events surveillance (see CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE, ADVERSE REACTIONS, DOSAGE AND ADMINISTRATION, and CLINICAL STUDIES).Geriatric UseOf the total number of subjects
who received cefuroxime axetil in 20 clinical studies of cefuroxime axetil, 375
were 65 and over while 151 were 75 and over. No overall differences in safety or
effectiveness were observed between these subjects and younger adult subjects.
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 elderly
and younger adult patients. Other reported clinical experience has not
identified differences in responses between the elderly and younger adult
patients.
Adverse Reactions
CEFUROXIME AXETIL TABLETS IN CLINICAL TRIALS: Multiple-Dose
Dosing Regimens: 7 to 10 Days Dosing:
Using
multiple doses of cefuroxime axetil tablets, 912 patients were treated with
cefuroxime axetil (125 to 500 mg twice daily). There were no deaths or permanent
disabilities thought related to drug toxicity. Twenty (2.2%) patients
discontinued medication due to adverse events thought by the investigators to be
possibly, probably, or almost certainly related to drug toxicity. Seventeen
(85%) of the 20 patients who discontinued therapy did so because of
gastrointestinal disturbances, including diarrhea, nausea, vomiting, and
abdominal pain. The percentage of cefuroxime axetil tablet-treated patients who
discontinued study drug because of adverse events was very similar at daily
doses of 1,000, 500, and 250 mg (2.3%, 2.1%, and 2.2%, respectively). However,
the incidence of gastrointestinal adverse events increased with the higher
recommended doses. The following adverse events were thought by the
investigators to be possibly, probably, or almost certainly related to
cefuroxime axetil tablets in multiple-dose clinical trials (n = 912 cefuroxime
axetil-treated patients).
5-Day
Experience (see CLINICAL STUDIES section):
In clinical trials using cefuroxime axetil in a dose of 250 mg
twice daily in the treatment of secondary bacterial infections of acute
bronchitis, 399 patients were treated for 5 days and 402 patients were treated
for 10 days. No difference in the occurrence of adverse events was found between
the 2 regimens.
In Clinical Trials
for Early Lyme Disease With 20 Days Dosing:
Two multicenter trials
assessed cefuroxime axetil tablets 500 mg twice a day for 20 days. The most
common drug-related adverse experiences were diarrhea (10.6%of patients),
Jarisch-Herxheimer reaction (5.6%), and vaginitis (5.4%). Other adverse
experiences occurred with frequencies comparable to those reported with 7 to 10
days dosing.
Single-Dose Regimen for Uncomplicated
Gonorrhea: In clinical trials using a single dose of cefuroxime axetil
tablets, 1,061 patients were treated with the recommended dosage of cefuroxime
axetil (1,000 mg) for the treatment of uncomplicated gonorrhea. There were no
deaths or permanent disabilities thought related to drug toxicity in these
studies. The following adverse events were thought by the investigators
to be possibly, probably, or almost certainly related to cefuroxime axetil in
1,000 mg single-dose clinical trials of cefuroxime axetil tablets in the
treatment of uncomplicated gonorrhea conducted in the United States.
POSTMARKETING EXPERIENCE WITH CEFUROXIME AXETIL PRODUCTS
In
addition to adverse events reported during clinical trials, the following events
have been identified during clinical practice in patients treated with
cefuroxime axetil tablets or with cefuroxime axetil for oral suspension and were
reported spontaneously. Data are generally insufficient to allow an estimate of
incidence or to establish causation.
General:
The following hypersensitivity reactions have
been reported: anaphylaxis, angioedema, pruritus, rash, serum sickness-like
reaction, urticaria.
Gastrointestinal:
Pseudomembranous colitis (see WARNINGS).
Hematologic:
Hemolytic anemia,
leukopenia, pancytopenia, thrombocytopenia, and increased prothrombin
time.
Hepatic:
Hepatic impairment including hepatitis and cholestasis,
jaundice.
Neurologic:
Seizure.
Skin:
Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal
necrolysis.
Urologic:
Renal dysfunction.
CEPHALOSPORIN-CLASS
ADVERSE REACTIONS
In addition to the adverse reactions uled
above that have been observed in patients treated with cefuroxime axetil, the
following adverse reactions and altered laboratory tests have been reported for
cephalosporin-class antibiotics: toxic nephropathy, aplastic anemia, hemorrhage,
increased BUN, increased creatinine, false-positive test for urinary glucose,
increased alkaline phosphatase, neutropenia, elevated bilirubin, and
agranulocytosis. Several cephalosporins have been implicated in
triggering seizures, particularly in patients with renal impairment when the
dosage was not reduced (see DOSAGE AND
ADMINISTRATIONand OVERDOSAGE). If seizures associated with drug
therapy occur, the drug should be discontinued. Anticonvulsant therapy can be
given if clinically indicated.
Overdosage
Overdosage of cephalosporins can cause cerebral irritation leading to
convulsions. Serum levels of cefuroxime can be reduced by hemodialysis and
peritoneal dialysis.
Dosage And Administration
NOTE: CEFUROXIME AXETIL TABLETS AND CEFUROXIME AXETIL FOR ORAL
SUSPENSION ARE NOT BIOEQUIVALENT AND ARE NOT SUBSTITUTABLE ON A
MILLIGRAM-PER-MILLIGRAM BASIS (SEE CLINICAL
PHARMACOLOGY).
Table 4. Cefuroxime Axetil Tablets (May be administered without regard
to meals.)
Pediatric
Patients (who can swallow tablets whole)
Acute otitis media
250 mg b.i.d.
10
Acute bacterial maxillary sinusitis
250 mg b.i.d.
10
* The safety and effectiveness of cefuroxime axetil administered for less
than 10 days in patients with acute exacerbations of chronic bronchitis
have not been established.
Patients With Renal Failure: The safety and efficacy
of cefuroxime axetil in patients with renal failure have not been established.
Since cefuroxime is renally eliminated, its half-life will be prolonged in
patients with renal failure.
How Supplied
Cefuroxime Axetil Tablets, USP 250 mg
of cefuroxime (as cefuroxime axetil), are white to off-white, uncoated,
capsule-shaped tablets with “A33” debossed on one side and plain on the other
side.
Bottles of 20
NDC 54868-4987-0
Bottles of 30
NDC 54868-4987-1
Cefuroxime Axetil Tablets, USP 500 mg
of cefuroxime (as cefuroxime axetil), are white to off-white, uncoated,
capsule-shaped tablets with “A34” debossed on one side and plain on the other
side.
Bottles of 15
NDC 54868-5022-2
Bottles of 20
NDC 54868-5022-1
Bottles of 30
NDC 54868-5022-0
Bottles of 60
NDC 54868-5022-3
Store at 20° to 25°C (68° to 77°F);
excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room
Temperature]. Replace cap securely after each opening.
Clinical Studies
Cefuroxime Axetil Tablets: Acute Bacterial
Maxillary Sinusitis:
One adequate and well-controlled study was
performed in patients with acute bacterial maxillary sinusitis. In this study
each patient had a maxillary sinus aspirate collected by sinus puncture before
treatment was initiated for presumptive acute bacterial sinusitis. All patients
had to have radiographic and clinical evidence of acute maxillary sinusitis. As
shown in the following summary of the study, the general clinical effectiveness
of cefuroxime axetil tablets was comparable to an oral antimicrobial agent that
contained a specific betalactamase inhibitor in treating acute maxillary
sinusitis. However, sufficient microbiology data were obtained to demonstrate
the effectiveness of cefuroxime axetil tablets in treating acute bacterial
maxillary sinusitis due only to Streptococcus pneumoniae
or non-beta-lactamase–producing Haemophilus
influenzae. An insufficient number of beta-lactamase–producing Haemophilus influenzae and Moraxella
catarrhalis isolates were obtained in this trial to adequately evaluate
the effectiveness of cefuroxime axetil tablets in the treatment of acute
bacterial maxillary sinusitis due to these 2 organisms. This study
enrolled 317 adult patients, 132 patients in the United States and 185 patients
in South America. Patients were randomized in a 1:1 ratio to cefuroxime axetil
250 mg twice daily or an oral antimicrobial agent that contained a specific
beta-lactamase inhibitor. An intent-to-treat analysis of the submitted clinical
data yielded the following results:
Table 5. Clinical Effectiveness of Cefuroxime Axetil Tablets Compared
to Beta-Lactamase Inhibitor-Containing Control Drug in the Treatment of Acute
Bacterial Maxillary Sinusitis
U.S. Patients*
South American Patients†
Cefuroxime Axetil(n =
49)
Control(n = 43)
Cefuroxime Axetil (n = 87)
Control(n = 89)
Clinical success(cure + improvement)
65%
53%
77%
74%
Clinical cure
53%
44%
72%
64%
Clinical improvement
12%
9%
5%
10%
* 95%Confidence interval around the success difference [-0.08, +0.32].
† 95%Confidence interval around the success difference
[-0.1, +0.16].
In this trial and in a
supporting maxillary puncture trial, 15 evaluable patients had
non-beta-lactamase–producing Haemophilus influenzae
as the identified pathogen. Ten (10) of these 15 patients (67%) had their
pathogen (non-beta-lactamase-producing Haemophilus
influenzae) eradicated. Eighteen (18) evaluable patients had Streptococcus pneumoniae as the identified pathogen.
Fifteen (15) of these 18 patients (83%) had their pathogen (Streptococcus pneumoniae) eradicated.
Safety:
The incidence of
drug-related gastrointestinal adverse events was statistically significantly
higher in the control arm (an oral antimicrobial agent that contained a specific
beta-lactamase inhibitor) versus the cefuroxime axetil arm (12%versus 1%,
respectively; P<.001), particularly drug-related
diarrhea (8%versus 1%, respectively; P =
.001).
Early Lyme Disease:
Two adequate and well-controlled studies were performed in
patients with early Lyme disease. In these studies all patients had to present
with physician-documented erythema migrans, with or without systemic
manifestations of infection. Patients were randomized in a 1:1 ratio to a 20-day
course of treatment with cefuroxime axetil 500 mg twice daily or doxycycline 100
mg 3 times daily. Patients were assessed at 1 month posttreatment for success in
treating early Lyme disease (Part I) and at 1 year posttreatment for success in
preventing the progression to the sequelae of late Lyme disease (Part
II). A total of 355 adult patients (181 treated with cefuroxime axetil
and 174 treated with doxycycline) were enrolled in the 2 studies. In order to
objectively validate the clinical diagnosis of early Lyme disease in these
patients, 2 approaches were used:1) blinded expert reading of photographs, when
available, of the pretreatment erythema migrans skin lesion; and 2) serologic
confirmation (using enzyme-linked immunosorbent assay [ELISA] and immunoblot
assay [“Western” blot]) of the presence of antibodies specific to Borrelia burgdorferi, the etiologic agent of Lyme disease.
By these procedures, it was possible to confirm the physician diagnosis of early
Lyme disease in 281 (79%) of the 355 study patients. The efficacy data
summarized below are specific to this “validated” patient subset, while the
safety data summarized below reflect the entire patient population for the 2
studies. Analysis of the submitted clinical data for evaluable patients
in the “validated” patient subset yielded the following results:
Table 6. Clinical Effectiveness of Cefuroxime Axetil Tablets Compared
to Doxycycline in the Treatment of Early Lyme Disease
Part I
(1 Month Posttreatment)*
Part II (1
Year Posttreatment)†
Cefuroxime Axetil (n = 125)
Doxycycline (n = 108)
Cefuroxime Axetil (n = 105‡)
Doxycycline (n = 83‡)
Satisfactory clinical outcome§
91%
93%
84%
87%
Clinical cure/success
72%
73%
73%
73%
Clinical improvement
19%
19%
10%
13%
* 95%confidence interval around the satisfactory difference for Part I (-0.08, +0.05).
† 95%confidence interval around the satisfactory difference for Part II (-0.13, +0.07).
‡
n’s include patients assessed as unsatisfactory clinical outcomes
(failure + recurrence) in Part I (cefuroxime axetil tablets - 11 [5
failure, 6 recurrence]; doxycycline - 8 [6 failure, 2 recurrence]).
§ Satisfactory clinical outcome includes cure + improvement
(Part I) and success + improvement (Part II).
Cefuroxime axetil and
doxycycline were effective in prevention of the development of sequelae of late
Lyme disease.
Safety:
Drug-related adverse events affecting the skin were reported
significantly more frequently by patients treated with doxycycline than by
patients treated with cefuroxime axetil (12%versus 3%, respectively; P = .002), primarily reflecting the statistically
significantly higher incidence of drug-related photosensitivity reactions in the
doxycycline arm versus the cefuroxime axetil arm (9%versus 0%, respectively;
P<.001). While the incidence of drug-related
gastrointestinal adverse events was similar in the 2 treatment groups
(cefuroxime axetil - 13%; doxycycline - 11%), the incidence of drug-related
diarrhea was statistically significantly higher in the cefuroxime axetil arm
versus the doxycycline arm (11%versus 3%, respectively; P
= .005).
Secondary Bacterial
Infections of Acute Bronchitis:
Four randomized, controlled
clinical studies were performed comparing 5 days versus 10 days of cefuroxime
axetil for the treatment of patients with secondary bacterial infections of
acute bronchitis. These studies enrolled a total of 1,253 patients (CAE-516 n =
360; CAE-517 n = 177; CAEA4001 n = 362; CAEA4002 n = 354). The protocols for
CAE-516 and CAE-517 were identical and compared cefuroxime axetil 250 mg twice
daily for 5 days, cefuroxime axetil 250 mg twice daily for 10 days, and
AUGMENTIN® 500 mg 3 times daily for 10 days. These 2
studies were conducted simultaneously. CAEA4001 and CAEA4002 compared cefuroxime
axetil 250 mg twice daily for 5 days, cefuroxime axetil 250 mg twice daily for
10 days, and CECLOR® 250 mg 3 times daily for 10 days.
They were otherwise identical to CAE-516 and CAE-517 and were conducted over the
following 2 years. Patients were required to have polymorphonuclear cells
present on the Gram stain of their screening sputum specimen, but isolation of a
bacterial pathogen from the sputum culture was not required for inclusion. The
following table demonstrates the results of the clinical outcome analysis of the
pooled studies CAE-516/CAE-517 and CAEA4001/CAEA4002, respectively:
Table 7. Clinical Effectiveness of Cefuroxime Axetil Tablets 250 mg
Twice Daily in Secondary Bacterial Infections of Acute Bronchitis: Comparison of
5 Versus 10 Days’ Treatment Duration
CAE-516 andCAE-517*
CAEA4001 andCAEA4002†
5 day(n = 127)
10 day(n = 139)
5 day(n = 173)
10 day(n = 192)
Clinical success(cure +
improvement)
80%
87%
84%
82%
Clinical cure
61%
70%
73%
72%
Clinical improvement
19%
17%
11%
10%
* 95%Confidence interval around the success difference[-0.164, +0.029].
† 95%Confidence interval around the success
difference[-0.061, +0.103].
The response rates for
patients who were both clinically and bacteriologically evaluable were
consistent with those reported for the clinically evaluable
patients.
Safety:
In
these clinical trials, 399 patients were treated with cefuroxime axetil for 5
days and 402 patients with cefuroxime axetil for 10 days. No difference in the
occurrence of adverse events was observed between the 2 regimens.
References
National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for
Bacteria that Grow Aerobically. 3rd ed. Approved Standard NCCLS Document
M7-A3, Vol. 13, No. 25. Villanova, Pa: NCCLS; 1993.
National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility
Tests. 4th ed. Approved Standard NCCLS Document M2-A4, Vol. 10, No. 7.
Villanova, Pa: NCCLS; 1990.
AUGMENTIN® and
CECLOR® are registered trademarks of
GlaxoSmithKline.CLINITEST and CLINISTIX are registered trademarks of Ames
Division, Miles Laboratories, Inc.
Manufactured for:
Aurobindo Pharma USA, Inc.
2400 Route 130 NorthDayton,
NJ 08810 Manufactured by:
Aurobindo Pharma
Limited
Chitkul (v)-502 307, A.P., India
Relabeling and Repackaging by:
Physicians Total Care, Inc.Tulsa, OK 74146
Principal Display Panel
Cefuroxime Axetil Tablets, USP 250 mg
Cefuroxime Axetil Tablets, USP 500 mg
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