Cefuroxime

INDICATIONS AND USAGE Cefuroxime for Injection USP and Dextrose Injection USP 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 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 may be used concomitantly with an aminoglycoside (see PRECAUTIONS ). The recommended doses of both antibacterials 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 USP and Dextrose Injection USP and other antibacterial drugs, Cefuroxime for Injection USP and Dextrose Injection USP 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 USP and Dextrose Injection USP 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 antibacterials in surgery depends on the time of administration. Cefuroxime for Injection USP and Dextrose Injection USP should usually be given one-half to 1 hour before the operation to allow sufficient time to achieve effective antibacterial 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 antibacterial does not reduce the incidence of subsequent infections but will increase the possibility of adverse reactions and the de

CLINICAL PHARMACOLOGY Following IV doses of 750 mg and 1.5 g, serum concentrations were approximately 50 and 100 mcg/mL, respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2 mcg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively. There was no evidence of accumulation of cefuroxime in the serum following IV administration of 1.5 g doses every 8 hours to normal volunteers. The serum half-life after IV injection is approximately 80 minutes. Approximately 89% of a dose of cefuroxime is excreted by the kidneys over an 8-hour period, resulting in high urinary concentrations. Intravenous doses of 750 mg and 1.5 g produced urinary levels averaging 1,150 and 2,500 mcg/mL, respectively, during the first 8-hour period. The concomitant oral administration of probenecid with cefuroxime slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Cefuroxime is detectable in therapeutic concentrations in pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor. Cefuroxime is detectable in therapeutic concentrations in cerebrospinal fluid (CSF) of adults and pediatric patients with meningitis. The following table shows the concentrations of cefuroxime achieved in cerebrospinal fluid during multiple dosing of patients with meningitis. Table 1. Concentrations of Cefuroxime Achieved in Cerebrospinal Fluid During Multiple Dosing of Patients with Meningitis Patients Dose Number of Patients Mean (Range) CSF Cefuroxime Concentrations (mcg/mL) Achieved Within 8 Hours Post Dose Pediatric patients (4 weeks to 6.5 years) 200 mg/kg/day, divided q 6 hours 5 6.6 (0.9–17.3) Pediatric patients (7 months to 9 years) 200 to 230 mg/kg/day, divided q 8 hours 6 8.3 (<2–22.5) Adults 1.5 grams q 8 hours 2 5.2 (2.7–8.9) Adults 1.5 grams q 6 hours 10 6.0 (1.5–13.5) Cefuroxime is approximately 50% bound to serum protein. Microbiology Mechanism of Action Cefuroxime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefuroxime has activity in the presence of some beta-Iactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria. Resistance Resistance to cefuroxime is primarily through hydrolysis by beta-Iactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability. Interaction with Other Antimicrobials In an in vitro study antagonistic effects have been observed with the combination of chloramphenicol and cefuroxime. Antimicrobial Activity Cefuroxime has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section: Gram-negative bacteria Enterobacter spp. Escherichia coli Klebsiella spp. Haemophilus influenzae Neisseria meningitidis Neisseria gonorrhoeae Gram-positive bacteria Staphylococcus aureus Streptococcus pneu

DOSAGE AND ADMINISTRATION This product is intended for intravenous administration only. Dosage: Adults: The usual adult dosage range for cefuroxime 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 cefuroxime therapy. A course of oral antibacterials was administered when appropriate following the completion of parenteral administration of cefuroxime. 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. 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 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 2 ). Table 2: Dosage of Cefuroxime 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 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 1 (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) × (140 - age) 72 × serum creatinine (mg/dL) Females: 0.85 × male value Note: As with antibacterial therapy in general, administration of Cefuroxime for Injection USP and Dextrose Injection USP 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. 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 antibacterials was administered to pediatric patients following the completion of parenteral administration of cefuroxime. In cases of bacterial meningitis, a larger dosage of cefuroxime is recommended, 200 to 240 mg/kg/day intraven

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 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: In addition to the adverse events reported during clinical trials, the following events have been observed during clinical practice in patients treated with cefuroxime and were reported spontaneously. Data are generally insufficient to allow an estimate of incidence or to establish causation. Immune System Disorders: Angioedema, acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction. Neurologic System Disorders: Seizure. Cephalosporin-class Adverse Reactions: In addition to the adverse reactions listed above that have been observed in patients treated with cefuroxime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibacterials: Adverse Reactions: Vomiting, abdominal pain, colitis, vaginitis including vaginal candidiasis, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, and hemorrhage. Several cephalosporins, including cefuroxime, 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.

WARNINGS BEFORE THERAPY WITH CEFUROXIME FOR INJECTION USP AND DEXTROSE INJECTION USP IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS, PENICILLINS OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS. ANTIBACTERIALS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. IF AN ALLERGIC REACTION TO CEFUROXIME OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES. Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefuroxime for Injection USP and Dextrose Injection USP, 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 antibacterial 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 antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.

CONTRAINDICATIONS Cefuroxime for Injection USP and Dextrose Injection USP is contraindicated in patients with known allergy to the cephalosporin group of antibacterials. Solutions containing dextrose may be contraindicated in patients with hypersensitivity to corn products.

OVERDOSAGE Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.