Cefuroxime

INDICATIONS AND USAGE Cefuroxime for Injection is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases: Lower Respiratory Tract Infections , including pneumonia, caused by Streptococcus pneumoniae , Haemophilus influenzae (including ampicillin-resistant strains), Klebsiella spp., Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains), Streptococcus pyogenes , and Escherichia coli . Urinary Tract Infections caused by Escherichia coli and Klebsiella spp. Skin and Skin­-Structure Infections caused by Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains), Streptococcus pyogenes , Escherichia coli , Klebsiella spp., and Enterobacter spp. Septicemia caused by Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains), Streptococcus pneumoniae , Escherichia coli , Haemophilus influenzae (including ampicillin-resistant strains), and Klebsiella spp. Meningitis caused by Streptococcus pneumoniae , Haemophilus influenzae (including ampicillin-resistant strains), Neisseria meningitidis , and Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains). Gonorrhea: Uncomplicated and disseminated gonococcal infections due to Neisseria gonorrhoeae (penicillinase- and non–penicillinase-producing strains) in both males and females. Bone and Joint Infections caused by Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains). Clinical microbiological studies in skin and skin­-structure infections frequently reveal the growth of susceptible strains of both aerobic and anaerobic organisms. Cefuroxime for Injection has been used successfully in these mixed infections in which several organisms have been isolated. In certain cases of confirmed or suspected gram-positive or gram-negative sepsis or in patients with other serious infections in which the causative organism has not been identified, Cefuroxime for Injection may be used concomitantly with an aminoglycoside (see PRECAUTIONS ). The recommended doses of both antibiotics may be given depending on the severity of the infection and the patient's condition. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefuroxime for Injection and other antibacterial drugs, Cefuroxime for Injection 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. Prevention: The preoperative prophylactic administration of Cefuroxime for Injection may prevent the growth of susceptible disease-causing bacteria and thereby may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures (e.g., vaginal hysterectomy) that are classified as clean-contaminated or potentially contaminated procedures. Effective prophylactic use of antibiotics in surgery depends on the time of administration. Cefuroxime for Injection should usually be given one-half to 1 hour before the operation to allow sufficient time to achieve effective antibiotic concentrations in the wound tissues during the procedure. The dose should be repeated intraoperatively if the surgical procedure is lengthy. Prophylactic administration is usually not required after the surgical procedure ends and should be stopped within 24 hours. In the majority of surgical procedures, continuing prophylactic administration of any antibiotic does not reduce the incidence of subsequent infections but will increase the possibility of adverse reactions and the development of bacterial resistance. The perioperative use of Cefuroxime for Injection has also been effective during open heart surgery for surgical patients in whom infections at the operative site would present a serious risk. For these patients it is recommended that therapy with Cefuroxime for Injection be continued for at least 48 hours after the surgical procedure ends. If an infection is present, specimens for culture should be obtained for the identification of the causative organism, and appropriate antimicrobial therapy should be instituted.

DOSAGE AND ADMINISTRATION Dosage: Adults: The usual adult dosage range for Cefuroxime for Injection is 750 mg to 1.5 grams every 8 hours, usually for 5 to 10 days. In uncomplicated urinary tract infections, skin and skin­-structure infections, disseminated gonococcal infections, and uncomplicated pneumonia, a 750 mg dose every 8 hours is recommended. In severe or complicated infections, a 1.5 gram dose every 8 hours is recommended. In bone and joint infections, a 1.5-gram dose every 8 hours is recommended. In clinical trials, surgical intervention was performed when indicated as an adjunct to therapy with Cefuroxime for Injection. A course of oral antibiotics was administered when appropriate following the completion of parenteral administration of Cefuroxime for Injection. In life-threatening infections or infections due to less susceptible organisms, 1.5 grams every 6 hours may be required. In bacterial meningitis, the dosage should not exceed 3 grams every 8 hours. The recommended dosage for uncomplicated gonococcal infection is 1.5 grams given intramuscularly as a single dose at 2 different sites together with 1 gram of oral probenecid. For preventive use for clean-contaminated or potentially contaminated surgical procedures, a 1.5-gram dose administered intravenously just before surgery (approximately one-half to 1 hour before the initial incision) is recommended. Thereafter, give 750 mg intravenously or intramuscularly every 8 hours when the procedure is prolonged. For preventive use during open heart surgery, a 1.5 gram dose administered intravenously at the induction of anesthesia and every 12 hours thereafter for a total of 6 grams is recommended. Impaired Renal Function: A reduced dosage must be employed when renal function is impaired. Dosage should be determined by the degree of renal impairment and the susceptibility of the causative organism (see Table 4 ). Table 4. Dosage of Cefuroxime for Injection in Adults With Reduced Renal Function Creatinine Clearance mL/min) Dose Frequency > 20 750 mg - 1.5 grams q8h 10 - 20 750 mg q12h < 10 750 mg q24h Since Cefuroxime for Injection is dialyzable, patients on hemodialysis should be given a further dose at the end of the dialysis. When only serum creatinine is available, the following formula 4 (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function. Males: Creatinine clearance (mL/min) = Weight (kg) x (140 - age) 72 x serum creatinine (mg/dL) Females: 0.85 x male value Note: As with antibiotic therapy in general, administration of Cefuroxime for Injection should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended in infections caused by Streptococcus pyogenes in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment for several weeks; and doses smaller than those indicated above should not be used. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated. Pediatric Patients Above 3 Months of Age: Administration of 50 to 100 mg/kg/day in equally divided doses every 6 to 8 hours has been successful for most infections susceptible to Cefuroxime for Injection. The higher dosage of 100 mg/kg/day (not to exceed the maximum adult dosage) should be used for the more severe or serious infections. In bone and joint infections, 150 mg/kg/day (not to exceed the maximum adult dosage) is recommended in equally divided doses every 8 hours. In clinical trials, a course of oral antibiotics was administered to pediatric patients following the completion of parenteral administration of Cefuroxime for Injection. In cases of bacterial meningitis, a larger dosage of cefuroxime is recommended, 200 to 240 mg/kg/day intravenously in divided doses every 6 to 8 hours. In pediatric patients with renal insufficiency, the frequency of dosing should be modified consistent with the recommendations for adults. Preparation of Solution and Suspension: The directions for preparing Cefuroxime for Injection for both IV and IM use are summarized in Table 5 . For Intramuscular Use: Each 750-mg vial of Cefuroxime for Injection should be constituted with 3 mL of Sterile Water for Injection. Shake gently to disperse and withdraw completely the resulting suspension for injection. For Intravenous Use: Each 750-mg vial should be constituted with 8.3 mL of Sterile Water for Injection. Withdraw completely the resulting solution for injection. Each 1.5-gram vial should be constituted with 16 mL of Sterile Water for Injection, and the solution should be completely withdrawn for injection. Table 5. Preparation of Solution Strength Amount of Diluent to be Added (mL) Volume to be Withdrawn Approximate Cefuroxime Concentration (mg/mL) 750-mg Vial 3 (IM) Total Note: Cefuroxime for Injection is a suspension at IM concentrations. 225 750-mg Vial 8.3 (IV) Total 90 1.5-gram Vial 16.0 (IV) Total 90 Administration: After constitution, Cefuroxime for Injection may be given intravenously or by deep IM injection into a large muscle mass (such as the gluteus or lateral part of the thigh). Before injecting intramuscularly, aspiration is necessary to avoid inadvertent injection into a blood vessel. Intravenous Administration: The IV route may be preferable for patients with bacterial septicemia or other severe or life-threatening infections or for patients who may be poor risks because of lowered resistance, particularly if shock is present or impending. For direct intermittent IV administration, slowly inject the solution into a vein over a period of 3 to 5 minutes or give it through the tubing system by which the patient is also receiving other IV solutions. For intermittent IV infusion with a Y-type administration set, dosing can be accomplished through the tubing system by which the patient may be receiving other IV solutions. However, during infusion of the solution containing Cefuroxime for Injection, it is advisable to temporarily discontinue administration of any other solutions at the same site. For continuous IV infusion , a solution of Cefuroxime for Injection may be added to an IV infusion pack containing one of the following fluids: 0.9% Sodium Chloride Injection; 5% Dextrose Injection; 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; or 1/6 M Sodium Lactate Injection. Solutions of Cefuroxime for Injection, like those of most beta-lactam antibiotics, should not be added to solutions of aminoglycoside antibiotics because of potential interaction. However, if concurrent therapy with Cefuroxime for Injection and an aminoglycoside is indicated, each of these antibiotics can be administered separately to the same patient. Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete. Preparation for Administration: 1. Suspend container from eyelet support. 2. Remove protector from outlet port at bottom of container. 3. Attach administration set. Refer to complete directions accompanying set.

ADVERSE REACTIONS Cefuroxime is generally well-tolerated. The most common adverse effects have been local reactions following IV administration. Other adverse reactions have been encountered only rarely. Local Reactions: Thrombophlebitis has occurred with IV administration in 1 in 60 patients. Gastrointestinal: Gastrointestinal symptoms occurred in 1 in 150 patients and included diarrhea (1 in 220 patients) and nausea (1 in 440 patients). The onset of pseudomembranous colitis may occur during or after antibacterial treatment (see WARNINGS). Hypersensitivity Reactions: Hypersensitivity reactions have been reported in fewer than 1% of the patients treated with Cefuroxime for Injection and include rash (1 in 125). Pruritus, urticaria, and positive Coombs' test each occurred in fewer than 1 in 250 patients, and, as with other cephalosporins, rare cases of anaphylaxis, drug fever, erythema multiforme, interstitial nephritis, toxic epidermal necrolysis, and Stevens-Johnson syndrome have occurred. Blood: A decrease in hemoglobin and hematocrit has been observed in 1 in 10 patients and transient eosinophilia in 1 in 14 patients. Less common reactions seen were transient neutropenia (fewer than 1 in 100 patients) and leukopenia (1 in 750 patients). A similar pattern and incidence were seen with other cephalosporins used in controlled studies. As with other cephalosporins, there have been rare reports of thrombocytopenia. Hepatic: Transient rise in SGOT and SGPT (1 in 25 patients), alkaline phosphatase (1 in 50 patients), LDH (1 in 75 patients), and bilirubin (1 in 500 patients) levels has been noted. Kidney: Elevations in serum creatinine and/or blood urea nitrogen and a decreased creatinine clearance have been observed, but their relationship to cefuroxime is unknown. Postmarketing Experience with Cefuroxime for Injection: In addition to the adverse events reported during clinical trials, the following events have been observed during clinical practice in patients treated with Cefuroxime for Injection and were reported spontaneously. Data are generally insufficient to allow an estimate of incidence or to establish causation. Immune System Disorders: Cutaneous vasculitis. Neurologic: Seizure. Non-site specific: Angioedema. Cephalosporin-class Adverse Reactions: In addition to the adverse reactions listed above that have been observed in patients treated with Cefuroxime for Injection, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: Adverse Reactions: Vomiting, abdominal pain, colitis, vaginitis including vaginal candidiasis, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, hemorrhage. Several cephalosporins, including Cefuroxime for Injection, have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see DOSAGE AND ADMINISTRATION ). If seizures associated with drug therapy should occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated. Altered Laboratory Tests: Prolonged prothrombin time, pancytopenia, agranulocytosis. To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceutical Corp. at 1-877-233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.