Cefzil

During the first 4-hour period after drug administration, the average urine concentrations following the 250 mg, 500 mg, and 1 g doses were approximately 170 µg/mL, 450 µg/mL and 600 µg/mL, respectively.

The average plasma half-life in normal subjects is 1.3 hours. Plasma protein binding is approximately 36% and is independent of concentration in the range of 2 to 20 µg/mL. There is no evidence of accumulation of cefprozil in the plasma in individuals with normal renal function following multiple oral doses of up to 1 g every 8 hours for 10 days.

Renal Insufficiency: In patients with reduced renal function, the plasma half-life prolongation is related to the degree of the renal dysfunction and may be prolonged up to 5.2 hours. In patients with complete absence of renal function, the plasma half-life of cefprozil averaged 5.9 hours. The half-life is shortened during hemodialysis to 2.1 hours. Excretion pathways in patients with markedly impaired renal function have not been determined (see Precautions and Dosage).

Hepatic Insufficiency: In patients with impaired hepatic function, no differences in pharmacokinetic parameters were observed, when compared to normal control subjects.

Geriatrics: Following administration of a single 1 g dose of cefprozil, the average AUC observed in healthy elderly subjects (≥65 years of age) was approximately 35 to 60% higher than that of healthy young adults and the average AUC in females was approximately 15 to 20% higher than in males. The magnitude of these age and gender-related variations in the pharmacokinetics of cefprozil are not sufficient to necessitate dosage adjustments.

Children: Comparable pharmacokinetic parameters of cefprozil are observed between pediatric patients (6 months to 12 years) and adults following oral administration. The maximum plasma concentrations are achieved at 1 to 2 hours after dosing. The plasma elimination half-life is approximately 1.5 hours. The AUC of cefprozil to pediatric patients after 7.5, 15 and 30 mg/kg doses is similar to that observed in normal adult subjects after 250, 500 and 1000 mg doses, respectively.

Pharyngitis/tonsillitis caused by group A β-hemolytic (GABHS) S. pyogenes.

Substantial data establishing the efficacy of cefprozil in the subsequent prevention of rheumatic fever are not available at present, although no case was reported during its evaluation in over 978 pediatric and 831 adult patients in controlled clinical trials.

Otitis media caused by S. pneumoniae, H. influenzae. M. (Branhamella) catarrhalis.

Acute sinusitis caused by S. pneumoniae, H. influenzae, (beta-lactamase positive and negative strains), and M. (Branhamella) catarrhalis.

Uncomplicated skin and skin-structure infections caused by S. aureus (including penicillinase-producing strains) and S. pyogenes.

Uncomplicated urinary tract infections (including acute cystitis) caused by E. coli, K. pneumoniae, P. mirabilis.

Cultures and susceptibility studies should be performed when appropriate.

Cefprozil has not been studied in the chronically ill or institutionalized elderly subjects. In these subjects, drug clearance by the kidney may be reduced even with normal serum creatinine clearance. Reduction of dose or of frequency of administration may be indicated.

Nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporin antibiotics. Concomitant administration of probenecid doubled the area under the curve for cefprozil.

If an aminoglycoside is used concurrently with cefprozil, especially if high dosages of the former are used or if therapy is prolonged, renal function should be monitored because of the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics.

Less than 1% of a maternal dose is excreted in human milk. Caution should be exercised when CEFZIL is administered to a nursing mother. Consideration should be given to temporary discontinuation of nursing and use of formula feeding.

The use of CEFZIL in the treatment of acute sinusitis in these age groups is supported by evidence from adequate and well-controlled studies of cefprozil in adults and from pediatric pharmacokinetic studies.

Safety and effectiveness in children below the age of 6 months have not been established. Accumulation of other cephalosporin antibiotics in newborn infants (resulting from prolonged drug half-life in this age group) has been reported.

Evaluation of renal status before and during therapy is recommended, especially in seriously ill patients. In patients with known or suspected renal impairment (see Dosage), 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 patients with creatinine clearance values ≤30 mL/min because high and/or prolonged plasma antibiotic concentrations can occur from usual doses in such individuals. 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.

Positive direct Coombs' tests have been reported during treatment with cephalosporin antibiotics.

Cefprozil should be prescribed with caution in individuals with a history of gastrointestinal disease particularly colitis.

Reproduction studies have been performed in mice, rats, and rabbits at doses 14, 7 and 0.7 times the maximum human daily dose (1000 mg) based upon mg/m², and have revealed no evidence of harm to the fetus due to cefprozil. 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 the potential benefit justifies the potential risk.

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 (glucose oxidase) for glycosuria. 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.

Each 5 mL of constituted, bubble-gum flavored solution contains: anhydrous cefprozil 125 mg. Nonmedicinal ingredients: aspartame, citric acid, colloidal silicone dioxide, FD&C yellow No. 6, flavors (natural and artificial), glycine, microcrystalline cellulose, polysorbate 80, simethicone, sodium benzoate, sodium carboxymethylcellulose, sodium chloride and sucrose. Bottles of 75 and 100 mL.

Each white, caplet-shaped, film-coated tablet, engraved with 7721 on one side and with 500 on the other side, contains: anhydrous cefprozil 500 mg. Nonmedicinal ingredients: hydroxypropylmethylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, simethicone, sodium starch glycolate and titanium dioxide. Bottles of 100.

Store the tablets and powder for oral suspension at room temperature (15 to 30°C) and protect from light and excessive humidity.

Each 5 mL of constituted, bubble-gum flavored solution contains: anhydrous cefprozil 250 mg. Nonmedicinal ingredients: aspartame, citric acid, colloidal silicone dioxide, FD&C yellow No. 6, flavors (natural and artificial), glycine, microcrystalline cellulose, polysorbate 80, simethicone, sodium benzoate, sodium carboxymethylcellulose, sodium chloride and sucrose. Bottles of 75 and 100 mL.

Each light orange, caplet-shaped, film-coated tablet engraved with 7720 on one side and with 250 on the other side, contains: anhydrous cefprozil 250 mg. Nonmedicinal ingredients: FD&C yellow No. 6, hydroxypropylmethylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, simethicone, sodium starch glycolate and titanium dioxide. Bottles of 100.

C. difficile-associated disease (CDAD) has been reported with use of many antibacterial agents, including CEFZIL (cefprozil). CDAD may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea, or symptoms of colitis, pseudomembranous colitis, toxic megacolon, or perforation of colon subsequent to the administration of any antibacterial agent. CDAD has been reported to occur over 2 months after the administration of antibacterial agents.

Treatment with antibacterial agents may alter the normal flora of the colon and may permit overgrowth of C. difficile. C. difficile produces toxins A and B, which contribute to the development of CDAD. CDAD may cause significant morbidity and mortality. CDAD can be refractory to antimicrobial therapy.

If the diagnosis of CDAD is suspected or confirmed, appropriate therapeutic measures should be initiated. Mild cases of CDAD usually respond to discontinuation of antibacterial agents not directed against C. difficile. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial agent clinically effective against C. difficile. Surgical evaluation should be instituted as clinically indicated, as surgical intervention may be required in certain severe cases (see Adverse Effects).

slight elevations in BUN and serum creatinine.

Adverse reactions reported from post-marketing experience and which were not seen in the clinical trials include anaphylaxis, angioedema, serum sickness, colitis including pseudomembraneous colitis, erythema multiforme, fever, Stevens-Johnson syndrome, thrombocytopenia and exfoliative dermatitis. Tooth discoloration has been reported during post-marketing surveillance. The association between these events and Cefzil administration is unknown.

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. Toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, prolonged prothrombin time, positive Coombs' tests, 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 Overdose). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

genital pruritus (0.8%) and vaginitis (0.7%).

Dizziness, hyperactivity, headache, nervousness, insomnia, confusion, and drowsiness have been reported rarely (<1%) and causal relationship is uncertain. All were reversible.

diarrhea (2.7%), nausea (2.3%), vomiting (1.4%) and abdominal pain (0.9%).

transiently decreased leukocyte count and eosinophilia.

rash (1.2%), erythema (0.1%), pruritus (0.3%) and urticaria (0.07%). 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.

elevations of AST, ALT, alkaline phosphatase, and bilirubin.

Transitory abnormalities in clinical laboratory test results of uncertain etiology have been reported during clinical trials as follows:

Since no case of overdosage has been reported to date, no specific information on symptoms or treatment of overdosage is available. In animal toxicology studies, single doses as high as 5000 mg/kg were without serious or lethal consequences.

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.