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:

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.

Last updated on RxList: 10/3/2007

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 (including β-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 (including β-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.

CEFZIL is administered orally.

Population/Infection	Dosage(mg)	Duration(days)
ADULTS (13 years and older)
UPPER RESPIRATORY TRACT
Pharyngitis/Tonsillitis	500 q24h	10a
Acute Sinusitis	250 q12h or	10
(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	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
a In the treatment of infections due to Streptococcus pyogenes, CEFZIL 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.

Creatinine Clearance (mL/min)	Dosage (mg)	Dosing Interval
30-120	standard	standard
0-29*	50% of standard	standard
* 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.

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

Bristol-Myers Squibb Company, Princeton, New Jersey 08543. USA. Rev March 2007. FDA Rev date: 9/14/2007

Last updated on RxList: 10/3/2007

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.

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.

Last updated on RxList: 10/3/2007

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.

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.

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.

Last updated on RxList: 10/3/2007

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

Last updated on RxList: 10/3/2007

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.)

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%
*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 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.

		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)
an=11; bn=5; cn =9; 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 β-lactamase-producing strains) NOTE: Cefprozil is inactive against methicillin-resistant staphylococci. Streptococcus pneumoniae Streptococcus pyogenes

Aerobic gram-negative microorganisms: Haemophilus influenzae (including β-lactamase-producing strains) Moraxella (Branhamella) catarrhalis (including β-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 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 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 β-lactamase-producing strains)	Proteus mirabilis Salmonella spp. Shigellaspp. Vibriospp.
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^1,2 (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

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.

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 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.

Last updated on RxList: 10/3/2007

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.

Last updated on RxList: 10/3/2007

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CEFPROZIL - ORAL

(seff-PRO-zill)

COMMON BRAND NAME(S): Cefzil

USES: Cefprozil is used to treat a wide variety of bacterial infections. This medication is known as a cephalosporin antibiotic. It works by stopping the growth of bacteria.

This antibiotic treats only bacterial infections. It will not work for viral infections (e.g., common cold, flu). Unnecessary use or overuse of any antibiotic can lead to its decreased effectiveness.

HOW TO USE: Take this medication by mouth usually once or twice daily, or as directed by your doctor. You may take this medicine with food if stomach upset occurs. Dosage is based on your medical condition and response to therapy. In children, the dosage is also based on weight.

Antibiotics work best when the amount of medicine in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals.

Continue to take this medication until the full-prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early may allow bacteria to continue to grow, which may result in a relapse of the infection.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Nausea, vomiting, diarrhea, stomach pain, or dizziness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: mental/mood changes, unusual tiredness/weakness.

Tell your doctor immediately if any of these rare but very serious side effects occur: yellowing of the eyes/skin, severe stomach/abdominal pain, persistent nausea/vomiting, dark urine, change in the amount of urine, signs of new infection (e.g., fever, persistent sore throat), easy bruising/bleeding.

This medication may rarely cause a severe intestinal condition (pseudomembranous colitis) due to a resistant bacteria. This condition may occur while receiving therapy or even weeks to months after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have the following symptoms because these products may make them worse. Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, blood/mucus in your stool.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection (oral or vaginal fungal infection). Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge or other new symptoms.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking cefprozil, tell your doctor or pharmacist if you are allergic to it; or to penicillins or other cephalosporin antibiotics (e.g., cephalexin); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, intestinal disease (colitis).

This drug may make you dizzy; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages.

Caution is advised when using this drug in the elderly because they may be more sensitive to its effects.

Caution is advised when using this drug in children because they may be more sensitive to its effects, especially rash.

This medication should be used only when clearly needed during pregnancy. Discuss the risk and benefits with your doctor.

This medication passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: live bacterial vaccines, probenecid.

This medication may decrease the effectiveness of combination-type birth control pills. This can result in pregnancy. You may need to use an additional form of reliable birth control while using this medication. Consult your doctor or pharmacist for details.

This medication may affect the results of certain lab tests. It may cause false positive results with certain diabetic urine testing products (cupric sulfate-type) and false negative results with certain blood glucose tests. Make sure laboratory personnel and your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include seizures.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless told to do so by your doctor. A different medication may be necessary in those cases.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.