To reduce the development of drug-resistant bacteria and maintain the
effectiveness of cefprozil tablets and other antibacterial drugs, cefprozil
tablets should be used only to treat or prevent infections that are proven or
strongly suspected to be caused by bacteria.
Description
Cefprozil is a semi-synthetic broad-spectrum
cephalosporin antibiotic.
Cefprozil is a cis and trans isomeric mixture (≥90% cis). The chemical name
for the monohydrate is
(6R,7R)-7-[(R)-2-amino-2-(p-hydroxyphenyl)acetamido]-8-oxo-3-propenyl-5-thia-1-azabicyclo
[4.2.0]oct-2-ene-2- carboxylic acid monohydrate, and the structural formula is:
Cefprozil is a white to yellowish powder with a molecular
formula for the monohydrate of C18H19N3O5S.H2O and a molecular weight of 407.45.
Cefprozil tablets are intended for oral administration.
Cefprozil tablets contain cefprozil equivalent to 250 mg or 500 mg of
anhydrous cefprozil. In addition, each tablet contains the following inactive
ingredients: magnesium stearate, methylcellulose, microcrystalline cellulose,
sodium starch glycolate and titanium dioxide. The 250 mg tablet also contains FD and C Yellow No. 6 Aluminum Lake.
Clinical Pharmacology
The pharmacokinetic data were derived from the capsule
formulation; however, bioequivalence has been demonstrated for the oral
solution, capsule, tablet, and suspension formulations under fasting
conditions.
Following oral administration of cefprozil to fasting subjects, approximately
95% of the dose was absorbed. The average plasma half-life in normal subjects
was 1.3 hours, while the steady-state volume of distribution was estimated to be
0.23 L/kg. The total body clearance and renal clearance rates were approximately
3 mL/min/kg and 2.3 mL/min/kg, respectively.
Average peak plasma concentrations after administration of 250 mg, 500 mg, or
1 g doses of cefprozil to fasting subjects were approximately 6.1, 10.5, and
18.3 mcg/mL, respectively, and were obtained within 1.5 hours after dosing.
Urinary recovery accounted for approximately 60% of the administered dose. (See
Table.)
Dosage (mg)
Mean Plasma Cefprozil
Concentrations (mcg/mL)*
8 hour Urinary Excretion
(%)
Peak appx. 1.5 h
4 h
8 h
250 mg
6.1
1.7
0.2
60%
500 mg
10.5
3.2
0.4
62%
1000 mg
18.3
8.4
1.0
54%
*Â Data represent mean values of 12 healthy
volunteers.
During the first 4 hour period after drug administration, the average urine
concentrations following 250 mg, 500 mg, and 1 g doses were approximately 700
mcg/mL, 1000 mcg/mL, and 2900 mcg/mL, respectively.
Administration of cefprozil with food did not affect the extent of absorption
(AUC) or the peak plasma concentration (Cmax) of
cefprozil. However, there was an increase of 0.25 to 0.75 hours in the time to
maximum plasma concentration of cefprozil (Tmax).
The bioavailability of the capsule formulation of cefprozil was not affected
when administered 5 minutes following an antacid.
Plasma protein binding is approximately 36% and is independent of
concentration in the range of 2 mcg/mL to 20 mcg/mL.
There was no evidence of accumulation of cefprozil in the plasma in
individuals with normal renal function following multiple oral doses of up to
1000 mg every 8 hours for 10 days.
In patients with reduced renal function, the plasma half-life may be
prolonged up to 5.2 hours depending on the degree of the renal dysfunction. In
patients with complete absence of renal function, the plasma half-life of
cefprozil has been shown to be as long as 5.9 hours. The half-life is shortened
during hemodialysis. Excretion pathways in patients with markedly impaired renal
function have not been determined. (See PRECAUTIONS
and DOSAGE AND
ADMINISTRATION.)
In patients with impaired hepatic function, the half-life increases to
approximately 2 hours. The magnitude of the changes does not warrant a dosage
adjustment for patients with impaired hepatic function.
Healthy geriatric volunteers (≥ 65 years old) who received a single 1 g dose
of cefprozil had 35% to 60% higher AUC and 40% lower renal clearance values
compared with healthy adult volunteers 20 to 40 years of age. The average AUC in
young and elderly female subjects was approximately 15% to 20% higher than in
young and elderly male subjects. The magnitude of these age- and gender-related
changes in the pharmacokinetics of cefprozil is not sufficient to necessitate
dosage adjustments.
Adequate data on CSF levels of cefprozil are not available.
Comparable pharmacokinetic parameters of cefprozil are observed between
pediatric patients (6 months to 12 years) and adults following oral
administration of selected matched doses. The maximum concentrations are
achieved at 1 to 2 hours after dosing. The plasma elimination half-life is
approximately 1.5 hours. In general, the observed plasma concentrations of
cefprozil in pediatric patients at the 7.5, 15, and 30 mg/kg doses are similar
to those observed within the same time frame in normal adult subjects at the
250, 500 and 1000 mg doses, respectively. The comparative plasma concentrations
of cefprozil in pediatric patients and adult subjects at the equivalent dose
level are presented in the table below.
Mean (SD) Plasma Cefprozil
Concentrations (mcg/mL)
Population
Dose
1Â h
2Â h
4Â h
6Â h
T½ (h)
children
7.5Â mg/kg
4.70
3.99
0.91
0.23 a
0.94
(n=18)
(1.57)
(1.24)
(0.30)
(0.13)
(0.32)
adults
250Â mg
4.82
4.92
1.70b
0.53
1.28
(n=12)
(2.13)
(1.13)
(0.53)
(0.17)
(0.34)
children
15Â mg/kg
10.86
8.47
2.75
0.61c
1.24
(n=19)
(2.55)
(2.03)
(1.07)
(0.27)
(0.43)
adults
500Â mg
8.39
9.42
3.18d
1.00d
1.29
(n=12)
(1.95)
(0.98)
(0.76)
(0.24)
(0.14)
children
30Â mg/kg
16.69
17.61
8.66
--
2.06
(n=10)
(4.26)
(6.39)
(2.70)
(0.21)
adults
1000Â mg
11.99
16.95
8.36
2.79
1.27
(n=12)
(4.67)
(4.07)
(4.13)
(1.77)
(0.12)
an=11Â Â bn=5Â Â cn=9Â Â dn=11
Microbiology:
Cefprozil has in vitro activity against a broad
range of gram-positive and gram-negative bacteria. The bactericidal action of
cefprozil results from inhibition of cell-wall synthesis. Cefprozil has been
shown 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. Aerobic
Gram-Positive Microorganisms:
Staphylococcus aureus
(including ß-lactamase-producing strains)
NOTE: Cefprozil is inactive against
methicillin-resistant staphylococci.
The following in vitro data are available;
however, their clinical significance is unknown. Cefprozil exhibits in vitro minimum inhibitory concentrations (MICs) of 8
mcg/mL or less against most (≥90%) strains of the following microorganisms;
however, the safety and effectiveness of cefprozil in treating clinical
infections due to these microorganisms have not been established in adequate and
well-controlled clinical trials. Aerobic
Gram-Positive Microorganisms:
Enterococcus durans
Enterococcus faecalis
Listeria monocytogenes
Staphylococcus epidermidis
Staphylococcus saprophyticus
Staphylococcus warneri
Streptococcus agalactiae
Streptococci (Groups C, D, F, and G)
viridans group Streptococci
NOTE: Cefprozil is inactive against Enterococcus faecium. Aerobic
Gram-Negative Microorganisms:
Citrobacter diversus
Escherichia coli
Klebsiella pneumoniae
Neisseria gonorrhoeae
(including ß-lactamase-producing strains)
Proteus mirabilis
Salmonella spp.
Shigella spp .
Vibrio spp.
NOTE: Cefprozil is inactive against most strains of
Acinetobacter, Enterobacter, Morganella morganii, Proteus
vulgaris, Providencia, Pseudomonas, and Serratia.
Anaerobic
Microorganisms:
Prevotella (Bacteroides) melaninogenicus
Clostridium difficile
Clostridium perfringens
Fusobacterium spp.
Peptostreptococcus spp.
Propionibacterium acnes
NOTE: Most strains of the Bacteroides fragilis group are resistant to
cefprozil. Susceptibility
Tests:
Dilution Techniques: Quantitative methods are used to determine
antimicrobial minimal inhibitory concentrations (MICs). These MICs provide
estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs
should be determined using a standardized procedure. Standardized procedures are
based on a dilution method1,2 (broth or agar) or
equivalent with standardized inoculum concentrations and standardized
concentrations of cefprozil powder. The MIC values should be interpreted
according to the following criteria:
MICÂ (mcg/mL)
Interpretation
≤8
         Susceptible        (S)
16
         Intermediate        (I)
≥32
         Resistant           (R)
A report of "Susceptible" indicates that the pathogen is likely to be
inhibited if the antimicrobial compound in the blood reaches the concentrations
usually achievable. A report of "Intermediate" indicates that the result should
be considered equivocal, and, if the microorganism is not fully susceptible to
alternative, clinically feasible drugs, the test should be repeated. This
category implies possible clinical applicability in body sites where the drug is
physiologically concentrated or in situations where high dosage of drug can be
used. This category also provides a buffer zone which prevents small
uncontrolled technical factors from causing major discrepancies in
interpretation. A report of "Resistant" indicates that the pathogen is not
likely to be inhibited if the antimicrobial compound in the blood reaches the
concentrations usually achievable; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory
control microorganisms to control the technical aspects of the laboratory
procedures. Standard cefprozil powder should provide the following MIC
values:
         Microorganism
MICÂ (mcg/mL)
         Enterococcus faecalis ATCC 29212
4-16
         Escherichia coli ATCC 25922
1-4
         Haemophilus influenzae ATCC 49766
1-4
         Staphylococcus aureus ATCC 29213
0.25-1
         Streptococcus pneumoniae ATCC 49619
0.25-1
Diffusion Techniques: Quantitative methods that require
measurement of zone diameters also provide reproducible estimates of the
susceptibility of bacteria to antimicrobial compounds. One such standardized
procedure3 requires the use of standardized inoculum
concentrations. This procedure uses paper disks impregnated with 30 mcg
cefprozil to test the susceptibility of microorganisms to cefprozil.
Reports from the laboratory providing results of the standard single-disk
susceptibility test with a 30 mcg cefprozil disk should be interpreted according
to the following criteria:
Zone diameter (mm)
Interpretation
≥18
           Susceptible          (S)
15-17
          Intermediate         (I)
≤14
           Resistant             (R)
Interpretation should be as stated above for results using dilution
techniques. Interpretation involves correlation of the diameter obtained in the
disk test with the MIC for cefprozil.
As with standardized dilution techniques, diffusion methods require the use
of laboratory control microorganisms that are used to control the technical
aspects of the laboratory procedures. For the diffusion technique, the 30 mcg
cefprozil disk should provide the following zone diameters in these laboratory
test quality control strains.
          Microorganism
Zone diameter (mm)
         Escherichia coli ATCC 25922
21-27
         Haemophilus influenzae ATCC 49766
20-27
         Staphylococcus aureus ATCC 25923
27-33
         Streptococcus pneumoniae ATCC 49619
25-32
Indications And Usage
Cefprozil 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: Upper Respiratory Tract: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. Cefprozil is generally effective in
the eradication of Streptococcus pyogenes from the
nasopharynx; however, substantial data establishing the efficacy of cefprozil in
the subsequent prevention of rheumatic fever are not available at present.
Otitis Media: Caused by Streptococcus
pneumoniae, Haemophilus influenzae (including ß-lactamase-producing
strains), and Moraxella (Branhamella) catarrhalis
(including ß-lactamase-producing strains). (See CLINICAL STUDIES.)
NOTE: In the treatment of otitis media due to ß-lactamase producing
organisms, cefprozil had bacteriologic eradication rates somewhat lower than
those observed with a product containing a specific ß-lactamase inhibitor. In
considering the use of cefprozil, lower overall eradication rates should be
balanced against the susceptibility patterns of the common microbes in a given
geographic area and the increased potential for toxicity with products
containing ß-lactamase inhibitors. Acute Sinusitis: Caused by Streptococcus
pneumoniae, Haemophilus influenzae (including
ß-lactamase producing strains), and Moraxella (Branhamella)
catarrhalis (including ß-lactamase-producing strains). Lower Respiratory Tract:Secondary Bacterial Infection of Acute Bronchitis and Acute
Bacterial Exacerbation of Chronic Bronchitis: Caused by Streptococcus
pneumoniae, Haemophilus influenzae (including ß-lactamase-producing
strains), and Moraxella (Branhamella) catarrhalis
(including ß-lactamase-producing strains). Skin and Skin Structure:Uncomplicated Skin and Skin-Structure Infections: Caused by Staphylococcus
aureus (including penicillinase producing strains) and Streptococcus pyogenes. Abscesses usually require surgical
drainage.
To reduce the development of drug-resistant bacteria and maintain the
effectiveness of cefprozil tablets and other antibacterial drugs, cefprozil
tablets 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.
Contraindications
Cefprozil is contraindicated in patients with known allergy to the cephalosporin
class of antibiotics.
Warnings
BEFORE THERAPY WITH CEFPROZIL
IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT
HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFPROZIL, CEPHALOSPORINS,
PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO
PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE
CROSS-SENSITIVITY AMONG ß-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY
OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN
ALLERGIC REACTION TO CEFPROZIL OCCURS, DISCONTINUE THE DRUG. 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
Cefprozil, 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
General: Prescribing cefprozil in the absence of 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.
In patients with known or suspected renal impairment (see DOSAGE AND ADMINISTRATION),careful clinical observation
and appropriate laboratory studies should be done prior to and during therapy.
The total daily dose of cefprozil should be reduced in these patients because
high and/or prolonged plasma antibiotic concentrations can occur in such
individuals from usual doses. Cephalosporins, including cefprozil, should be
given with caution to patients receiving concurrent treatment with potent
diuretics since these agents are suspected of adversely affecting renal
function.
Prolonged use of cefprozil may result in the overgrowth of nonsusceptible
organisms. Careful observation of the patient is essential. If superinfection
occurs during therapy, appropriate measures should be taken.
Cefprozil should be prescribed with caution in individuals with a history of
gastrointestinal disease particularly colitis.
Positive direct Coombs’ tests have been reported during treatment with
cephalosporin antibiotics.
Information For Patients:
Patients should be counseled that antibacterial
drugs including cefprozil should only be used to treat bacterial infections.
They do not treat viral infections (e.g., the common cold). When cefprozil are
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 cefprozil or other antibacterial drugs in the future.
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.
Drug Interactions Section
Nephrotoxicity has been reported following
concomitant administration of aminoglycoside antibiotics and cephalosporin
antibiotics. Concomitant administration of probenecid doubled the AUC for
cefprozil.
The bioavailability of the capsule formulation of cefprozil was not affected
when administered 5 minutes following an antacid.
Drug/laboratory Test Interactions:
Cephalosporin antibiotics may produce a false positive reaction for glucose in
the urine 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®). A false negative reaction
may occur in the ferricyanide test for blood glucose. The presence of cefprozil
in the blood does not interfere with the assay of plasma or urine creatinine by
the alkaline picrate method.
Carcinogenesis, Mutagenesis, Impairment Of Fertility:
Long term in vivo
studies have not been performed to evaluate the carcinogenic potential of
cefprozil.
Cefprozil was not found to be mutagenic in either the Ames Salmonella or E. coli WP2 urvA
reversion assays or the Chinese hamster ovary cell HGPRT forward gene mutation
assay and it did not induce chromosomal abnormalities in Chinese hamster ovary
cells or unscheduled DNA synthesis in rat hepatocytes in
vitro. Chromosomal aberrations were not observed in bone marrow cells
from rats dosed orally with over 30 times the highest recommended human dose
based upon mg/m2.
Impairment of fertility was not observed in male or female rats given oral
doses of cefprozil up to 18.5 times the highest recommended human dose based
upon mg/m2.
Pregnancy:
Teratogenic Effects- Pregnancy Category B: Reproduction studies have been performed in
rabbits, mice, and rats using oral doses of cefprozil of 0.8, 8.5, and 18.5
times the maximum daily human dose (1000 mg) based upon mg/m2, and have revealed no harm to the fetus. 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:
Cefprozil has not been studied for use during labor and delivery. Treatment
should only be given if clearly needed.
Nursing Mothers:
Small amounts of cefprozil (less than 0.3% of dose) have been detected in human milk
following administration of a single 1 gram dose to lactating women. The average
levels over 24 hours ranged from 0.25 to 3.3 mcg/mL. Caution should be exercised
when cefprozil tablets are administered to a nursing woman, since the effect of
cefprozil on nursing infants is unknown.
The safety and effectiveness of cefprozil in the treatment of otitis media
have been established in the age groups 6 months to 12 years. Use of cefprozil
for the treatment of otitis media is supported by evidence from adequate and
well-controlled studies of cefprozil in pediatric patients. (See CLINICAL STUDIES)
The safety and effectiveness of cefprozil in the treatment of
pharyngitis/tonsillitis or uncomplicated skin and skin-structure infections have
been established in the age groups 2 to 12 years. Use of cefprozil for the
treatment of these infections is supported by evidence from adequate and
well-controlled studies of cefprozil in pediatric patients.
The safety and effectiveness of cefprozil in the treatment of acute sinusitis
have been established in the age groups 6 months to 12 years. Use of cefprozil
in these age groups is supported by evidence from adequate and well-controlled
studies of cefprozil in adults.
Safety and effectiveness in pediatric patients below the age of 6 months have
not been established for the treatment of otitis media or acute sinusitis, or
below the age of 2 years for the treatment of pharyngitis/tonsillitis or
uncomplicated skin and skin-structure infections. However, accumulation of other
cephalosporin antibiotics in newborn infants (resulting from prolonged drug
half-life in this age group) has been reported.
Geriatric Use:
Of the more than 4500 adults treated with
cefprozil in clinical studies, 14% were 65 years and older, while 5% were 75
years and older. When geriatric patients received the usual recommended adult
doses, their clinical efficacy and safety were comparable to clinical efficacy
and safety in nongeriatric adult patients. Other reported clinical experience
has not identified differences in responses between elderly and younger
patients, but greater sensitivity of some older individuals to the effects of
cefprozil cannot be excluded (see CLINICAL
PHARMACOLOGY).
Cefprozil is known to be substantially excreted by the kidney, and the risk
of 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, care should be taken in dose selection and it may be useful to monitor
renal function. See DOSAGE AND ADMINISTRATION
for dosing recommendations for patients with impaired renal function.
Adverse Reactions
The adverse reactions to cefprozil are similar
to those observed with other orally administered cephalosporins. Cefprozil was
usually well tolerated in controlled clinical trials. Approximately 2% of
patients discontinued cefprozil therapy due to adverse events.
The most common adverse effects observed in patients treated with cefprozil
are: Gastrointestinal: Diarrhea (2.9%), nausea (3.5%), vomiting (1%),
and abdominal pain (1%). Hepatobiliary: Elevations of AST (SGOT) (2%), ALT (SGPT) (2%),
alkaline phosphatase (0.2%), and bilirubin values (less than 0.1%). As with some
penicillins and some other cephalosporin antibiotics, cholestatic jaundice has
been reported rarely. Hypersensitivity: Rash (0.9%), urticaria (0.1%). Such reactions
have been reported more frequently in children than in adults. Signs and
symptoms usually occur a few days after initiation of therapy and subside within
a few days after cessation of therapy. CNS: Dizziness (1%). Hyperactivity, headache,
nervousness, insomnia, confusion, and somnolence have been reported rarely
(less than 1%). All were reversible. Hematopoietic: Decreased leukocyte count (0.2%), eosinophilia
(2.3%). Renal: Elevated BUN (0.1%), serum creatinine
(0.1%). Other: Diaper rash and superinfection (1.5%), genital
pruritus and vaginitis (1.6%).
The following adverse events, regardless of established causal relationship
to cefprozil tablets, have been rarely reported during postmarketing
surveillance: anaphylaxis, angioedema, colitis (including pseudomembranous
colitis), erythema multiforme, fever, serum-sickness like reactions,
Stevens-Johnson syndrome, and thrombocytopenia. Cephalosporin Class Paragraph: In addition to the adverse reactions uled
above which have been observed in patients treated with cefprozil, the following
adverse reactions and altered laboratory tests have been reported for
cephalosporin-class antibiotics:
Several cephalosporins have been implicated in triggering seizures,
particularly in patients with renal impairment, when the dosage was not reduced.
(SeeDOSAGE AND ADMINISTRATION and OVERDOSAGE.)If seizures associated with drug therapy
occur, the drug should be discontinued. Anticonvulsant therapy can be given if
clinically indicated.
Overdosage Section
Single 5000 mg/kg oral doses of cefprozil
caused no mortality or signs of toxicity in adult, weanling, or neonatal rats,
or adult mice. A single oral dose of 3000 mg/kg caused diarrhea and loss of
appetite in cynomolgus monkeys, but no mortality.
Cefprozil is eliminated primarily by the kidneys. In case of severe
overdosage, especially in patients with compromised renal function, hemodialysis
will aid in the removal of cefprozil from the body.
Dosage And Administration
Cefprozil tablets are administered orally.
Population/Infection
Dosage (mg)
Duration (days)
 ADULTS (13 years and older)Â
    UPPER RESPIRATORY TRACT
        Pharyngitis/Tonsillitis
500Â q24h
10 a
        Acute Sinusitis
250 q12h or
10
        (For moderate to severe infections, the higher dose should be used)
500Â q12h
    LOWER RESPIRATORY TRACT
        Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial         Exacerbation of Chronic Bronchitis
500Â q12h
10
    SKIN AND SKIN STRUCTURE
        Uncomplicated Skin and Skin Structure Infections
250 q12h or
10
500 q24h or
500Â q12h
 CHILDREN (2 years-12 years)
    UPPER RESPIRATORY TRACT b
        Pharyngitis/Tonsillitis
7.5 mg/kg q12h
10 a
    SKIN AND SKIN STRUCTURE b
        Uncomplicated Skin and Skin Structure Infections
20 mg/kg q24h
10
 INFANTS and CHILDREN (6 months-12 years)
    UPPER RESPIRATORY TRACT b
        Otitis Media
15 mg/kg q12h
10
        (See INDICATIONS
AND USAGE and CLINICAL
STUDIES)
        Acute Sinusitis
7.5 mg/kg q12h or
10
        (For moderate to severe infections, the higher dose should be used)
15 mg/kg q12h
a In the treatment of infections due to Streptococcus
pyogenes, cefprozil for oral suspension should be administered for at least 10
days.
b Not to exceed recommended adult doses.
Renal
Impairment:
Cefprozil may be administered to patients with impaired renal function. The
following dosage schedule should be used.
*Cefprozil is in part removed by hemodialysis;
therefore, cefprozil should be administered after the completion of
hemodialysis.
Hepatic
Impairment:
No dosage adjustment is necessary for patients with impaired hepatic
function.
How Supplied
Cefprozil tablets USP, 250 mg and 500 mg are available as follows:Each white film-coated, oval tablet debossed with ‘LUPIN’ on one side and ‘500’
on the other side, contains the equivalent of 500 mg anhydrous cefprozil.
Bottles of 20 Tablets                         NDC 67296-0590-1
Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].
Clinical Studies
Study One:
In a controlled clinical study of acute otitis
media performed in the United States where significant rates of
ßlactamase- producing organisms were found, cefprozil was compared to an oral
antimicrobial agent that contained a specific ß-lactamase inhibitor. In this
study, using very strict evaluability criteria and microbiologic and clinical
response criteria at the 10-16 days post-therapy follow-up, the following
presumptive bacterial eradication/clinical cure outcomes (i.e., clinical
success) and safety results were obtained:
                                                                      U.S.
Acute Otitis Media Study
                                            Cefprozil vs β-lactamase
inhibitor-containing control drug
EFFICACY:
Pathogen
% of Cases with Pathogen(n=155)
Outcome
 S. pneumoniae
48.4%
  cefprozil success rate 5% better than control
 H. influenzae
35.5%
  cefprozil success rate 17% less than control
 M. catarrhalis
13.5%
  cefprozil success rate 12% less than control
 S. pyogenes
2.6%
                      cefprozil equivalent to control
 Overall
100.0%
cefprozil success rate 5% less than control
SAFETY:
The incidences of adverse events, primarily diarrhea and rash*, were clinically and statistically significantly higher in
the control arm versus the cefprozil arm.
Age Group
Cefprozil
Control
6 months-2 years
21%
41%
3-12 years
10%
19%
* The
majority of these involved the diaper area in young children.
Study Two:
In a controlled clinical study of acute otitis media
performed in Europe, cefprozil was compared to an oral antimicrobial
agent that contained a specific ß-lactamase inhibitor. As expected in a European
population, this study population had a lower incidence of ß-lactamase-producing
organisms than usually seen in U.S. trials. In this study, using very strict
evaluability criteria and microbiologic and clinical response criteria at the
10-16 days post-therapy follow-up, the following presumptive bacterial
eradication/clinical cure outcomes (i.e., clinical success) were obtained:
                                                                            European
Acute Otitis Media Study
                                                        Cefprozil vs
β-lactamase inhibitor-containing control drug
EFFICACY:
Pathogen
% of Cases with Pathogen(n=47)
Outcome
 S. pneumoniae
51.0%
cefprozil equivalent to control
 H. influenzae
29.8%
cefprozil equivalent to control
 M. catarrhalis
6.4%
cefprozil equivalent to control
 S. pyogenes
12.8%
cefprozil equivalent to control
 Overall
100.0%
cefprozil equivalent to control
SAFETY:
The incidence of adverse events in the cefprozil arm was comparable to the
incidence of adverse events in the control arm (agent that contained a specific
ß-lactamase inhibitor).
References
National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for
Bacteria that Grow Aerobically-Third Edition. Approved Standard NCCLS
Document M7-A3, Vol.13, No. 25, NCCLS, Villanova, PA, December 1993.
National Committee for Clinical Laboratory Standards. Methods for Antimicrobial Susceptibility Testing of Anaerobic
Bacteria-Third Edition. Approved Standard NCCLS Document M11-A3, Vol. 13,
No. 26, NCCLS, Villanova, PA, December 1993.
National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests
-Fifth Edition. Approved Standard NCCLS Document M2-A5, Vol. 13, No. 24,
NCCLS, Villanova, PA, December 1993.
Clintest® and
Clinistix® are registered trademarks of Bayer HealthCare
LLC.
Manufactured for:
                                                                        Manufactured
by                     Â
Lupin Pharmaceuticals,
Inc.                                       Lupin Limited
Baltimore, Maryland
21202Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Mumbai 400 098
United
States                                                                                INDIA
Revised: December, 2007
                                                         ID#: 213043
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