Cefzil

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

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

CEFZIL (cefprozil) 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 (cefprozil) and other antibacterial drugs, CEFZIL (cefprozil) 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 (cefprozil) is administered orally.

Renal Impairment

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

Hepatic Impairment

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

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

WARNINGS

BEFORE THERAPY WITH CEFZIL (cefprozil) IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFZIL (cefprozil) , CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-SENSITIVITY AMONG 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 (cefprozil) OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including CEFZIL (cefprozil) , and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS

General

Prescribing CEFZIL (cefprozil) in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

In patients with known or suspected renal impairment (see DOSAGE AND ADMINISTRATION), careful clinical observation and appropriate laboratory studies should be done prior to and during therapy. The total daily dose of 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 (cefprozil) , should be given with caution to patients receiving concurrent treatment with potent diuretics since these agents are suspected of adversely affecting renal function.

Prolonged use of CEFZIL (cefprozil) may result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

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

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

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 (cefprozil) 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 (cefprozil) for the treatment of otitis media is supported by evidence from adequate and well-controlled studies of cefprozil in pediatric patients. (See CLINICAL STUDIES.)

The safety and effectiveness of cefprozil in the treatment of pharyngitis/tonsillitis or uncomplicated skin and skin-structure infections have been established in the age groups 2 to 12 years. Use of CEFZIL (cefprozil) for the treatment of these infections is supported by evidence from adequate and well-controlled studies of cefprozil in pediatric patients.

The safety and effectiveness of cefprozil in the treatment of acute sinusitis have been established in the age groups 6 months to 12 years. Use of CEFZIL (cefprozil) in these age groups is supported by evidence from adequate and well-controlled studies of cefprozil in adults.

Safety and effectiveness in pediatric patients below the age of 6 months have not been established for the treatment of otitis media or acute sinusitis, or below the age of 2 years for the treatment of pharyngitis/tonsillitis or uncomplicated skin and skin-structure infections. However, accumulation of other cephalosporin antibiotics in newborn infants (resulting from prolonged drug half-life in this age group) has been reported.

Geriatric Use

Of the more than 4500 adults treated with CEFZIL (cefprozil) in clinical studies, 14% were 65 years and older, while 5% were 75 years and older. When geriatric patients received the usual recommended adult doses, their clinical efficacy and safety were comparable to clinical efficacy and safety in nongeriatric adult patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals to the effects of CEFZIL cannot be excluded (see CLINICAL PHARMACOLOGY).

CEFZIL (cefprozil) is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function. See DOSAGE AND ADMINISTRATION for dosing recommendations for patients with impaired renal function.

SIDE EFFECTS

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 (cefprozil) , 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.

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.

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.

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 (cefprozil) , 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.

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.