Cefoxitin and Dextrose

5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions including anaphylaxis and serious skin reactions. If an allergic reaction occurs, discontinue the drug. ( 5.1 ) Use in patients with renal impairment: Dosage adjustment required for patients with impaired renal function. ( 2.3 ) Clostridium difficile -associated diarrhea: May range from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. ( 5.2 ) 5.1 Hypersensitivity Reactions to Cefoxitin or other Beta-lactam Antibacterial Drugs Serious and occasionally fatal hypersensitivity reactions (e.g., anaphylaxis) have been reported in patients on β-lactam antibacterials, including cefoxitin [see Adverse Reactions (6.1) ] . These reactions are more likely to occur in individuals with a history of β-lactam hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Cefoxitin for Injection and Dextrose Injection is contraindicated in patients with a known hypersensitivity to Cefoxitin for Injection and Dextrose Injection or other β-lactam antibacterial drugs [see Contraindications (4) ] . Before initiating therapy with Cefoxitin for Injection and Dextrose Injection, inquire about previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue Cefoxitin for Injection and Dextrose Injection and institute appropriate therapy. 5.2 Clostridium difficile -associated Diarrhea Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefoxitin for Injection and Dextrose Injection, 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. 5.3 Risk of Development of Drug-resistant Bacteria Prescribing Cefoxitin for Injection and Dextrose Injection in the absence of a 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. Prolonged use of Cefoxitin for Injection and Dextrose Injection may result in overgrowth of non-susceptible microorganisms. Repeated evaluation of the patient's condition is essential. Should superinfection occur during therapy, appropriate measures should be taken. 5.4 Drug/Laboratory Test Interactions As with cephalothin, high concentrations of cefoxitin (>100 mcg/mL) may interfere with measurement of serum and urine creatinine levels by Jaffé reaction, and produce false increases of modest degree in the levels of creatinine reported. Serum samples from patients treated with cefoxitin should not be analyzed for creatinine if withdrawn within 2 hours of drug administration. High concentrations of cefoxitin in the urine may interfere with measurement of urinary 17-hydroxy-corticosteroids by the Porter-Silber reaction, and produce false increases of modest degree in the levels reported. A false-positive reaction for glucose in the urine may occur. This has been observed with CLINITEST® reagent tablets. 5.5 Patients with a History of Gastrointestinal Disease Cefoxitin for Injection and Dextrose Injection is not recommended in individuals with a history of gastrointestinal disease, particularly colitis. 5.6 Patients with Overt or Known Subclinical Diabetes Mellitus or Carbohydrate Intolerance As with other dextrose-containing solutions, Cefoxitin for Injection and Dextrose Injection should be monitored if Cefoxitin for Injection and Dextrose Injection is prescribed in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of labeling: • Hypersensitivity Reactions to Cefoxitin or other Beta-lactam Antibacterial Drugs [see Warnings and Precautions (5.1)] • Use in Patients with Renal Impairment [see Dosage and Administration (2.3) , Use in Specific Populations (8.6)] • Clostridium difficile -associated Diarrhea [see Warnings and Precautions (5.2)] • Risk of Development of Drug-resistant Bacteria [see Warnings and Precautions (5.3)] • Drug/Laboratory Test Interactions [see Warnings and Precautions (5.4)] • Patients with a History of Gastrointestinal Disease [see Warnings and Precautions (5.5) ] • Patients with Overt or Known Subclinical Diabetes Mellitus or Carbohydrate Intolerance [see Warnings and Precautions (5.6) ] The most common adverse reactions have been local reactions following intravenous injection. Local Reactions Thrombophlebitis has occurred with intravenous administration. Skin and Subcutaneous Tissue Disorders Rash (including exfoliative dermatitis and toxic epidermal necrolysis), urticaria, flushing, pruritus, eosinophilia, fever, dyspnea, and other allergic reactions including anaphylaxis, interstitial nephritis and angioedema have been noted. Cardiovascular Disorders Hypotension. Gastrointestinal Disorders Diarrhea, including documented pseudomembranous colitis which can appear during or after antibiotic treatment. Nausea and vomiting have been reported. Nervous System Disorders Possible exacerbation of myasthenia gravis. Blood and Lymphatic System Disorders Eosinophilia, leukopenia including granulocytopenia, neutropenia, anemia including hemolytic anemia, thrombocytopenia, and bone marrow depression. A positive direct Coombs test may develop in some individuals, especially those with azotemia. Hepatobiliary Disorders Reversible elevation in SGOT, SGPT, serum LDH, and serum alkaline phosphatase; and jaundice have been reported. Renal and Urinary Disorders Elevations in serum creatinine and/or blood urea nitrogen levels have been observed. Acute renal failure has been reported. Most common adverse reactions: Local reactions. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact B. Braun Medical Inc. at 1-800-854-6851 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Cephalosporin-class Adverse Reactions In addition to the adverse reactions listed above which have been observed in patients treated with cefoxitin, the following adverse reactions and altered laboratory test results have been reported for cephalosporin class antibacterials: pruritus, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, vomiting, abdominal pain, colitis, superinfection, vaginitis including vaginal candidiasis, renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage, elevated bilirubin, pancytopenia, and neutropenia. Several cephalosporins, including Cefoxitin for Injection and Dextrose Injection, have been implicated in triggering seizures, particularly in patients with renal impairment, when the dosage was not reduced [ see Dosage and Administration (2.3) and Overdosage (10 ) ] . If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.