o 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: 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.

ment 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.

e and clinical studies ) acute sinusitis 7.5 mg/kg q12h or 10 (for moderate to severe infections, the higher dose should be used) 15 mg/kg q12h 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 to 120 standard standard 0 to 29 cefprozil is in part removed by hemodialysis; therefore, cefprozil should be administered after the completion of hemodialysis. 50% of standard standard hepatic impairment: no dosage adjustment is necessary for patients with impaired hepatic function.

ss, 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, serumsickness 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.

ata represent mean values of 12 healthy volunteers. 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 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 max ) of cefprozil. however, there was an increase of 0.25 to 0.75 hours in the time to maximum plasma concentration of cefprozil (t max ). the bioavailability of the capsule formulation of cefprozil was not affected when administered 5 minutes following an antacid. plasma protein binding is approximately 36% and is independent of concentration in the range of 2 mcg/ml to 20 mcg/ml. there was no evidence of accumulation of cefprozil in the plasma in individuals with normal renal function following multiple oral doses of up to 1000 mg every 8 hours for 10 days. in patients with reduced renal function, the plasma half-life may be prolonged up to 5.2 hours depending on the degree of the renal dysfunction. in patients with complete absence of renal function, the plasma half-life of cefprozil has been shown to be as long as 5.9 hours. the half-life is shortened during hemodialysis. excretion pathways in patients with markedly impaired renal function have not been determined. (see precautions and dosage and administration .) in patients with impaired hepatic function, the half-life increases to approximately 2 hours. the magnitude of the changes does not warrant a dosage adjustment for patients with impaired hepatic function. healthy geriatric volunteers (≥65 years old) who received a single 1 g dose of cefprozil had 35% to 60% higher auc and 40% lower renal clearance values compared with healthy adult volunteers 20 to 40 years of age. the average auc in young and elderly female subjects was approximately 15% to 20% higher than in young and elderly male subjects. the magnitude of these age- and gender-related changes in the pharmacokinetics of cefprozil is not sufficient to necessitate dosage adjustments. adequate data on csf levels of cefprozil are not available. comparable pharmacokinetic parameters of cefprozil are observed between pediatric patients (6 months to 12 years) and adults following oral administration of selected matched doses. the maximum concentrations are achieved at 1 to 2 hours after dosing. the plasma elimination half-life is approximately 1.5 hours. in general, the observed plasma concentrations of cefprozil in pediatric patients at the 7.5, 15, and 30 mg/kg doses are similar to those observed within the same time frame in normal adult subjects at the 250, 500, and 1000 mg doses, respectively. the comparative plasma concentrations of cefprozil in pediatric patients and adult subjects at the equivalent dose level are presented in the table below. mean (sd) plasma cefprozil a n=11 b n=5 c n=9 d n=11 concentrations (mcg/ml) population dose 1 h 2 h 4 h 6 h t½ (h) children 7.5 mg/kg 4.70 3.99 0.91 0.23 a 0.94 (n=18) (1.57) (1.24) (0.30) (0.13) (0.32) adults 250 mg 4.82 4.92 1.70 b 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 c 1.24 (n=19) (2.55) (2.03) (1.07) (0.27) (0.43) adults 500 mg 8.39 9.42 3.18 d 1.00 d 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 usage section. 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 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 ( mcg / ml ) interpretation ≤8 susceptible (s) 16 intermediate (i) ≥32 resistant (r) a report of "susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. a report of "intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. this category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. this category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. a report of "resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected. standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. standard cefprozil powder should provide the following mic values: microorganism mic ( mcg / ml ) enterococcus faecalis atcc 29212 4 to 16 escherichia coli atcc 25922 1 to 4 haemophilus influenzae atcc 49766 1 to 4 staphylococcus aureus atcc 29213 0.25 to 1 streptococcus pneumoniae atcc 49619 0.25 to 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 3 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 to 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 to 27 haemophilus influenzae atcc 49766 20 to 27 staphylococcus aureus atcc 25923 27 to 33 streptococcus pneumoniae atcc 49619 25 to 32

il 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 to 2 years 21% 41% 3 to 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 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 to 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).