CEFPROZIL

INDICATIONS AND USAGE Cefprozil tablets are 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 influenza (including β-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including β-lactamase-producing strains). LOWER RESPIRATORY TRACT 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 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.

DOSAGE AND ADMINISTRATION Cefprozil tablets are administered orally. Population/Infection Dosage (mg) Duration (days) ADULTS (13 years and older) UPPER RESPIRATORY TRACT Pharyngitis/Tonsillitis 500 q24h 10 In the treatment of infections due to Streptococcus pyogenes , cefprozil should be administered for at least 10 days. Acute Sinusitis (For moderate to severe infections, the higher dose should be used) 250 q12h or 500 q12h 10 LOWER RESPIRATORY TRACT 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 to 12 years) UPPER RESPIRATORY TRACT Not to exceed recommended adult doses. Pharyngitis/Tonsillitis 7.5 mg/kg q12h 10 SKIN AND SKIN STRUCTURE Uncomplicated Skin and Skin Structure Infections 20 mg/kg q24h 10 INFANTS & CHILDREN (6 months to 12 years) UPPER RESPIRATORY TRACT 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. 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.

CONTRAINDICATIONS Cefprozil is contraindicated in patients with known allergy to the cephalosporin class of antibiotics.

WARNINGS BEFORE THERAPY WITH CEFPROZIL IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO 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 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 cefprozil tablets, 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.

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.

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 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.

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/m 2 , 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.