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Generic Name: cefprozil
Dosage Form: tablets, oral suspension

Cefzil® (CEFPROZIL) Tablets
250 mg and 500 mg
Cefzil® (CEFPROZIL) for Oral Suspension
125 mg/5 mL and 250 mg/5 mL

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefzil® and other antibacterial drugs, Cefzil should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Cefzil Description

Cefzil (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:

Slideshow: The Shocking Truth About Antibiotic Resistance

Cefprozil is a white to yellowish powder with a molecular formula for the monohydrate of C18H19N3O5S•H2O and a molecular weight of 407.45.

Cefzil Tablets and Cefzil for Oral Suspension are intended for oral administration.

Cefzil Tablets contain cefprozil equivalent to 250 mg or 500 mg of anhydrous cefprozil. In addition, each tablet contains the following inactive ingredients: cellulose, hypromellose, magnesium stearate, methylcellulose, simethicone, sodium starch glycolate, polyethylene glycol, polysorbate 80, sorbic acid, and titanium dioxide. The 250 mg tablets also contain FD&C Yellow No. 6.

Cefzil for Oral Suspension contains cefprozil equivalent to 125 mg or 250 mg anhydrous cefprozil per 5 mL constituted suspension. In addition, the oral suspension contains the following inactive ingredients: aspartame, cellulose, citric acid, colloidal silicone dioxide, FD&C Red No. 3, flavors (natural and artificial), glycine, polysorbate 80, simethicone, sodium benzoate, sodium carboxymethylcellulose, sodium chloride, and sucrose.

Cefzil - 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 µg/mL, respectively, and were obtained within 1.5 hours after dosing. Urinary recovery accounted for approximately 60% of the administered dose. (See Table.)

*Data represent mean values of 12 healthy volunteers.
Dosage
(mg)
Mean Plasma Cefprozil
Concentrations (µg/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%

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 µg/mL, 1000 µg/mL, and 2900 µg/mL, respectively.

Administration of Cefzil tablet or suspension formulation 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 µg/mL to 20 µg/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.

an=11; bn=5; cn=9; dn=11.
  Mean (SD) Plasma Cefprozil Concentrations (µg/mL)  
Population Dose 1 h 2 h 4 h 6 h T1/2(h)
children
(n=18)
7.5 mg/kg 4.70
(1.57)
3.99
(1.24)
0.91
(0.30)
0.23a
(0.13)
0.94
(0.32)
adults
(n=12)
250 mg 4.82
(2.13)
4.92
(1.13)
1.70b
(0.53)
0.53
(0.17)
1.28
(0.34)
children
(n=19)
15 mg/kg 10.86
(2.55)
8.47
(2.03)
2.75
(1.07)
0.61c
(0.27)
1.24
(0.43)
adults
(n=12)
500 mg 8.39
(1.95)
9.42
(0.98)
3.18d
(0.76)
1.00d
(0.24)
1.29
(0.14)
children
(n=10)
30 mg/kg 16.69
(4.26)
17.61
(6.39)
8.66
(2.70)
2.06
(0.21)
adults
(n=12)
1000 mg 11.99
(4.67)
16.95
(4.07)
8.36
(4.13)
2.79
(1.77)
1.27
(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 USAGE section.

Aerobic gram-positive microorganisms: Aerobic gram-negative microorganisms:
Staphylococcus aureus (including β-lactamase-
producing strains)
Haemophilus influenzae (including β-lactamase-producing strains)
      NOTE:  Cefprozil is inactive against
      methicillin-resistant staphylococci.
Moraxella (Branhamella) catarrhalis (includingβ-lactamase-producing strains)
Streptococcus pneumoniae  
Streptococcus pyogenes  

The following in vitro data are available; however, their clinical significance is unknown. Cefprozil exhibits in vitro minimum inhibitory concentrations (MICs) of 8 µg/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 Staphylococcus warneri
Enterococcus faecalis Streptococcus agalactiae
Listeria monocytogenes Streptococci (Groups C,D,F, and G)
Staphylococcus epidermidis viridans group Streptococci
Staphylococcus saprophyticus  
   NOTE:  Cefprozil is inactive against
   Enterococcus faecium.
 
Aerobic gram-negative microorganisms:
Citrobacter diversus Proteus mirabilis
Escherichia coli Salmonella spp.
Klebsiella pneumoniae Shigella spp.
Neisseria gonorrhoeae (including β-lactamase-producing strains) Vibrio spp.
   NOTE:  Cefprozil is inactive against most strains of Acinetobacter, EnterobacterMorganella morganii,
   Proteus vulgaris, Providencia, Pseudomonas, and Serratia.
Anaerobic microorganisms:
Prevotella (Bacteroides) melaninogenicus Fusobacterium spp.
Clostridium difficile Peptostreptococcus spp.
Clostridium perfringens 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:

MIC (µg/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 MIC (µg/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 µg 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-µg 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-µg 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 for Cefzil

Cefzil is 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 β-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including β-lactamase-producing strains). (See CLINICAL STUDIES.)

 
NOTE: In the treatment of otitis media due to β-lactamase producing organisms, cefprozil had bacteriologic eradication rates somewhat lower than those observed with a product containing a specific β-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 β-lactamase inhibitors.

Acute Sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (includingβ-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 β-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (includingβ-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 Cefzil and other antibacterial drugs, Cefzil 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

Cefzil (cefprozil) is contraindicated in patients with known allergy to the cephalosporin class of antibiotics.

Warnings

BEFORE THERAPY WITH Cefzil IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO Cefzil, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-SENSITIVITY AMONG β-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 Cefzil 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 Cefzil, 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 Cefzil 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 Cefzil (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 Cefzil, 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 Cefzil 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

Phenylketonurics: Cefzil for oral suspension contains phenylalanine 28 mg per 5 mL (1 teaspoonful) constituted suspension for both the 125 mg/5 mL and 250 mg/5 mL dosage forms.

Patients should be counseled that antibacterial drugs including Cefzil should only be used to treat bacterial infections. They do not treat viral infections (eg, the common cold). When Cefzil 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 Cefzil 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 (eg, 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.

Clinitest® and Clinistix® are registered trademarks of the Bayer HealthCare LLC.

Carcinogenesis, Mutagenesis, and 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 (<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 µg/mL. Caution should be exercised when Cefzil is administered to a nursing woman, since the effect of cefprozil on nursing infants is unknown.

Pediatric Use

(See INDICATIONS AND USAGE and 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 Cefzil 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 Cefzil 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 Cefzil 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 Cefzil 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 Cefzil cannot be excluded (see CLINICAL PHARMACOLOGY).

Cefzil 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 (<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 (<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 Cefzil, 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.

Cefzil Dosage and Administration

Cefzil is administered orally.

aIn the treatment of infections due to Streptococcus pyogenes, Cefzil should be administered for at least 10 days.
bNot to exceed recommended adult doses.
Population/Infection Dosage
(mg)
Duration
(days)
ADULTS (13 years and older)    
    UPPER RESPIRATORY TRACT
      Pharyngitis/Tonsillitis 500 q24h 10a
      Acute Sinusitis
      (For moderate to severe infections, the higher dose
      should be used)
250 q12h or
500 q12h
10
    LOWER RESPIRATORY TRACT
      Secondary Bacterial Infection of Acute Bronchitis and
       Acute Bacterial Exacerbation of Chronic Bronchitis
500 q12h 10
    SKIN AND SKIN STRUCTURE
      Uncomplicated Skin and Skin Structure Infections 250 q12h or
500 q24h or
500 q12h
10
CHILDREN (2 years–12 years)
    UPPER RESPIRATORY TRACTb
      Pharyngitis/Tonsillitis 7.5 mg/kg q12h 10a
    SKIN AND SKIN STRUCTUREb
      Uncomplicated Skin and Skin Structure Infections 20 mg/kg q24h 10
INFANTS & CHILDREN (6 months–12 years)
    UPPER RESPIRATORY TRACTb
      Otitis Media
      (See INDICATIONS AND USAGE and
      CLINICAL STUDIES)
15 mg/kg q12h 10
      Acute Sinusitis
      (For moderate to severe infections, the higher dose
       should be used)
7.5 mg/kg q12h or
15 mg/kg q12h
10

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.
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 is Cefzil Supplied

Cefzil® (cefprozil) Tablets

Each light orange film-coated tablet, imprinted with “7720” on one side and “250” on the other, contains the equivalent of 250 mg anhydrous cefprozil.

Bottles of 100 Tablets NDC 0087-7720-60

Each white film-coated tablet, imprinted with “7721” on one side and “500” on the other, contains the equivalent of 500 mg anhydrous cefprozil.

Bottles of 50 Tablets NDC 0087-7721-50
Bottles of 100 Tablets NDC 0087-7721-60

Store at controlled room temperature, 59°–86° F (15°–30° C).

Cefzil® (cefprozil) For Oral Suspension

Each 5 mL of constituted suspension contains the equivalent of 125 mg anhydrous cefprozil.

50 mL Bottle NDC 0087-7718-40
75 mL Bottle NDC 0087-7718-62
100 mL Bottle NDC 0087-7718-64

Each 5 mL of constituted suspension contains the equivalent of 250 mg anhydrous cefprozil.

50 mL Bottle NDC 0087-7719-40
75 mL Bottle NDC 0087-7719-62
100 mL Bottle NDC 0087-7719-64

All powder formulations for oral suspension contain cefprozil in a bubble-gum flavored mixture.

Reconstitution Directions for Oral Suspension

Prepare the suspension at the time of dispensing; for ease in preparation, add water in two portions and shake well after each aliquot.

Total Amount of Water Required for Reconstitution
Bottle Size Final Concentration
125 mg/5 mL
Final Concentration
250 mg/5mL
50 mL 36 mL 36 mL
75 mL 54 mL 54 mL
100 mL 72 mL 72 mL

After mixing, store in a refrigerator and discard unused portion after 14 days.

Store at 59°–77° F (15°–25° C) prior to constitution.

U.S. Patent No. 4,520,022

Clinical Studies

Study One:

In a controlled clinical study of acute otitis media performed in the United States where significant rates of β-lactamase-producing organisms were found, cefprozil was compared to an oral antimicrobial agent that contained a specific β-lactamase inhibitor. In this study, using very strict evaluability criteria and microbiologic and clinical response criteria at the 10 to 16 days post-therapy follow-up, the following presumptive bacterial eradication/clinical cure outcomes (ie, 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 21% 41%
3–12 years 10% 19%

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 β-lactamase inhibitor. As expected in a European population, this study population had a lower incidence of β-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 to 16 days post-therapy follow-up, the following presumptive bacterial eradication/clinical cure outcomes (ie, 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 β-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.

Bristol-Myers Squibb Company
Princeton, New Jersey 08543 USA

Rev March 2007

Cefzil 
cefprozil tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) 0087-7720
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
cefprozil (cefprozil) cefprozil 250 mg
Inactive Ingredients
Ingredient Name Strength
cellulose  
hypromellose  
magnesium stearate  
methylcellulose  
simethicone  
sodium starch glycolate  
polyethylene glycol  
polysorbate 80  
sorbic acid  
titanium dioxide  
FD&C Yellow No. 6  
Product Characteristics
Color ORANGE Score no score
Shape OVAL Size 15mm
Flavor Imprint Code 7720;250
Contains         
Coating true Symbol false
Packaging
# Item Code Package Description
1 NDC:0087-7720-60 100 TABLET, FILM COATED (100 TABLET) in 1 BOTTLE
Cefzil 
cefprozil tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) 0087-7721
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
cefprozil (cefprozil) cefprozil 500 mg
Inactive Ingredients
Ingredient Name Strength
cellulose  
hypromellose  
magnesium stearate  
methylcellulose  
simethicone  
sodium starch glycolate  
polyethylene glycol  
polysorbate 80  
sorbic acid  
titanium dioxide  
Product Characteristics
Color WHITE Score no score
Shape OVAL Size 17mm
Flavor Imprint Code 7721;500
Contains         
Coating true Symbol false
Packaging
# Item Code Package Description
1 NDC:0087-7721-50 50 TABLET, FILM COATED (50 TABLET) in 1 BOTTLE
2 NDC:0087-7721-60 100 TABLET, FILM COATED (100 TABLET) in 1 BOTTLE
Cefzil 
cefprozil powder, for suspension
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) 0087-7718
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
cefprozil (cefprozil) cefprozil 125 mg  in 5 mL
Inactive Ingredients
Ingredient Name Strength
aspartame  
cellulose  
citric acid  
colloidal silicone dioxide  
FD&C Red No. 3  
flavors (natural and artificial)  
glycine  
polysorbate 80  
simethicone  
sodium benzoate  
sodium carboxymethylcellulose  
sodium chloride  
sucrose  
phenylalanine  
Product Characteristics
Color      Score     
Shape Size
Flavor Imprint Code
Contains         
Coating false Symbol false
Packaging
# Item Code Package Description
1 NDC:0087-7718-40 50 mL (50 MILLILITER) in 1 BOTTLE
2 NDC:0087-7718-62 75 mL (75 MILLILITER) in 1 BOTTLE
3 NDC:0087-7718-64 100 mL (100 MILLILITER) in 1 BOTTLE
Cefzil 
cefprozil powder, for suspension
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) 0087-7719
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
cefprozil (cefprozil) cefprozil 250 mg  in 5 mL
Inactive Ingredients
Ingredient Name Strength
aspartame  
cellulose  
citric acid  
colloidal silicone dioxide  
FD&C Red No. 3  
flavors (natural and artificial)  
glycine  
polysorbate 80  
simethicone  
sodium benzoate  
sodium carboxymethylcellulose  
sodium chloride  
sucrose  
phenylalanine  
Product Characteristics
Color      Score     
Shape Size
Flavor Imprint Code
Contains         
Coating false Symbol false
Packaging
# Item Code Package Description
1 NDC:0087-7719-40 50 mL (50 MILLILITER) in 1 BOTTLE
2 NDC:0087-7719-62 75 mL (75 MILLILITER) in 1 BOTTLE
3 NDC:0087-7719-64 100 mL (100 MILLILITER) in 1 BOTTLE
Labeler - Bristol-Myers Squibb
Revised: 09/2007
 
Bristol-Myers Squibb
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