CEFPROZIL - cefprozil tablet

United States - English - NLM (National Library of Medicine)

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Active ingredient:
CEFPROZIL (UNII: 4W0459ZA4V) (CEFPROZIL ANHYDROUS - UNII:1M698F4H4E)
Available from:
Physicians Total Care, Inc.
INN (International Name):
CEFPROZIL
Composition:
CEFPROZIL ANHYDROUS 500 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
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 listed below: 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. 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 observe
Product summary:
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 54868-5756-0 Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].
Authorization status:
Abbreviated New Drug Application
Authorization number:
54868-5756-0

CEFPROZIL - cefprozil tablet

Physicians Total Care, Inc.

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CEFPROZIL TABLETS USP 250 mg and 500 mg

Rx only

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

H N O S.H O 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 & 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

8 hour Urinary Excretion (%)

Concentrations (mcg/mL)

Peak appx.

1.5 h

250 mg

500 mg

10.5

1000 mg

18.3

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 (C

) of cefprozil. However, there was an increase of 0.25 to 0.75 hours in the time to

maximum plasma concentration of cefprozil (T

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 PRECAUTIONSand 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

T½ (h)

children

7.5 mg/kg

4.70

3.99

0.91

0.23

0.94

(n=18)

(1.57)

(1.24)

(0.30)

(0.13)

(0.32)

adults

250 mg

4.82

4.92

1.70

0.53

1.28

(n=12)

(2.13)

(1.13)

(0.53)

(0.17)

(0.34)

children

15 mg/kg

10.86

8.47

2.75

0.61

1.24

(n=19)

(2.55)

(2.03)

(1.07)

(0.27)

(0.43)

n=11

n=11

(n=19)

(2.55)

(2.03)

(1.07)

(0.27)

(0.43)

adults

500 mg

8.39

9.42

3.18

1.00

1.29

(n=12)

(1.95)

(0.98)

(0.76)

(0.24)

(0.14)

children

30 mg/kg

16.69

17.61

8.66

2.06

(n=10)

(4.26)

(6.39)

(2.70)

(0.21)

adults

1000 mg

11.99

16.95

8.36

2.79

1.27

(n=12)

(4.67)

(4.07)

(4.13)

(1.77)

(0.12)

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 USAGEsection.

Aerobic Gram-Positive Microorganisms:

Staphylococcus aureus

(including ß-lactamase-producing strains)

NOTE: Cefprozil is inactive against methicillin-resistant staphylococci.

Streptococcus pneumoniae

Streptococcus pyogenes

Aerobic Gram-Negative Microorganisms:

Haemophilus influenzae

(including ß-lactamase-producing strains)

Moraxella (Branhamella) catarrhalis

(including ß-lactamase-producing strains)

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 method

(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:

MIC (mcg/mL)

Interpretation

≤8

Susceptible (S)

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

MIC (mcg/mL)

Enterococcus faecalis ATCC 29212

4-16

Escherichia coli ATCC 25922

Haemophilus influenzae ATCC 49766

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 procedure 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 listed 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:

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/m .

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/m .

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/m , 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 (<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.

Pediatric Use:

(See INDICATIONS AND USAGEand DOSAGE AND ADMINISTRATION.)

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:

Gas trointes tinal:

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

(<0.1%). As with some penicillins and some other cephalosporin antibiotics, cholestatic jaundice has

been reported rarely.

Hypers ens itivity:

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 (<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 listed 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:

Aplastic anemia, hemolytic anemia, hemorrhage, renal dysfunction, toxic epidermal necrolysis, toxic

nephropathy, prolonged prothrombin time, positive Coombs’ test, elevated LDH, pancytopenia,

neutropenia, agranulocytosis.

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal

impairment, when the dosage was not reduced. (See DOSAGE 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

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)

UPPER RESPIRATORY TRACT

Pharyngitis/Tonsillitis

500 q24h

Acute Sinusitis

250 q12h or

(For moderate to severe infections, the higher dose should be used)

500 q12h

LOWER RESPIRATORY TRACT

Secondary Bacterial Infection of Acute Bronchitis and

Acute Bacterial Exacerbation of Chronic Bronchitis

500 q12h

SKIN AND SKIN STRUCTURE

Uncomplicated Skin and Skin Structure Infections

250 q12h or

500 q24h or

500 q12h

CHILDREN (2 years-12 years)

UPPER RESPIRATORY TRACT

Pharyngitis/Tonsillitis

7.5 mg/kg q12h

SKIN AND SKIN STRUCTURE

Uncomplicated Skin and Skin Structure Infections

20 mg/kg q24h

INFANTS & CHILDREN (6 months-12 years)

UPPER RESPIRATORY TRACT

In the treatment of infections due to Streptococcus pyogenes, cefprozil tablets should be administered for at least 10

days.

Not to exceed recommended adult doses.

Otitis Media

15 mg/kg q12h

(See INDICATIONS AND USAGE and CLINICAL STUDIES)

Acute Sinusitis

7.5 mg/kg q12h or

(For moderate to severe infections, the higher dose should be used)

15 mg/kg q12h

Renal Impairment:

Cefprozil may be administered to patients with impaired renal function. The following dosage schedule

should be used.

Creatinine Clearance (mL/min)

Dosage (mg)

Dosing Interval

30-120

standard

standard

0-29

50% of standard

standard

Hepatic Impairment:

No dosage adjustment is necessary for patients with impaired hepatic function.

HOW SUPPLIED

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 54868-5756-0

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 ß-lactamase- 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.

The majority of these involved the diaper area in young children.

Age Group

Cefprozil

Control

6 months-2 years

3-12 years

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

1. 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.

2. 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.

3. 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

Lupin Pharmaceuticals, Inc. Lupin Limited

Baltimore, Maryland 21202 Mumbai 400 098

United States INDIA

Revised: December, 2007 ID#: 213043

Relabeling and Repackaging by:

Physicians Total Care, Inc.

Tulsa, Oklahoma 74146

PRINCIPAL DISPLAY PANEL

CEFPROZIL TABLETS USP

Rx Only

500 mg

CEFPROZIL

cefprozil tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:548 6 8 -5756 (NDC:6 8 18 0 -40 4)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Physicians Total Care, Inc.

Ingredient Name

Basis of Strength

Stre ng th

CEFPRO ZIL (UNII: 4W0 459 ZA4V) (CEFPROZIL ANHYDROUS - UNII:1M6 9 8 F4H4E)

CEFPROZIL ANHYDROUS

50 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

SO DIUM STARCH GLYCO LATE TYPE A PO TATO (UNII: 58 56 J3G2A2)

METHYLCELLULO SE ( 15 CPS) (UNII: NPU9 M2E6 L8 )

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

Product Characteristics

Color

WHITE

S core

no sco re

S hap e

OVAL

S iz e

18 mm

Flavor

Imprint Code

LUPIN;50 0

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:548 6 8 -5756 -0

20 in 1 BOTTLE

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 6 5276

0 2/0 5/20 0 7

Labeler -

Physicians T otal Care, Inc. (194123980)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Physicians To tal Care, Inc.

19 41239 8 0

relabel, repack

Revised: 5/2012

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