CEFEPIME- cefepime_injection, solution

Cefepime is an antibacterial drug. [See Microbiology (12. 4) Similar to other beta-lactam antibacterial drugs, the time that the unbound plasma concentration of cefepime exceeds the MIC of the infecting organism has been shown to best correlate with efficacy in animal models of infection. However, the pharmacokinetic/pharmacodynamic relationship for cefepime has not been evaluated in patients. Pharmacokinetic parameters for cefepime in healthy adult male volunteers (n=9) following single 30-minute intravenous infusions of cefepime 500 mg, 1 g, and 2 g are summarized in Table 6 Table 6: Mean Pharmacokinetic Parameters for Cefepime (+/-SD), Intravenous Administration CEFEPIME Parameter 500 mg IV 1 g IV 2 g IV C max 39. 3) AUC, hmcg/mL 70. 6) Number of subjects (male) 9 9 9 Distribution The average steady-state volume of distribution of cefepime is 18. The serum protein binding of cefepime is approximately 20% and is independent of its concentration in serum. Concentrations of cefepime achieved in specific tissues and body fluids are listed in Table 7 Table 7: Mean Concentrations of Cefepime in Specific Body Fluids (mcg/mL) or Tissues (mcg/g) Tissue or Fluid Dose/Route # of Patients Mean Time of Sample Post-Dose (h) Mean Concentration Blister Fluid 2 g IV 6 1. 4 mcg/mL Bronchial Mucosa 2 g IV 20 4. 1 mcg/g Sputum 2 g IV 5 4 7. 4 mcg/mL Urine 500 mg IV 8 0-4 292 mcg/mL 1 g IV 12 0-4 926 mcg/mL 2 g IV 12 0-4 3120 mcg/mL Bile 2 g IV 26 9. 8 mcg/mL Peritoneal Fluid 2 g IV 19 4. 3 mcg/mL Appendix 2 g IV 31 5. 2 mcg/g Gall Bladder 2 g IV 38 8. 9 mcg/g Prostate 2 g IV 5 1 31. 5 mcg/g Data suggest that cefepime does cross the inflamed blood-brain barrier. The clinical relevance of these data is uncertain at Metabolism and Excretion Cefepime is metabolized to N-methylpyrrolidine (NMP), which is rapidly converted to the N-oxide (NMP-N-oxide). Urinary recovery of unchanged cefepime accounts for approximately 85% of the administered dose. Less than 1% of the administered dose is recovered from urine as NMP, 6. 8% as NMP-N-oxide, and 2. 5% as an epimer of cefepime. Because renal excretion is a significant pathway of elimination, patients with renal dysfunction and patients undergoing hemodialysis require dosage adjustment [see Dosage and Administration (2) Specific Populations Patients with Renal Impairment Cefepime pharmacokinetics have been investigated in patients with various degrees of renal impairment (n=30). The average half-life in patients requiring hemodialysis was 13. 7) hours and in patients requiring continuous peritoneal dialysis was 19 (+/-2. Cefepime total body clearance decreased proportionally with creatinine clearance in patients with abnormal renal function, which serves as the basis for dosage adjustment recommendations in this group of patients [see Dosage and Administration (2) Patients with Hepatic Impairment The pharmacokinetics of cefepime were unaltered in patients with hepatic impairment who received a single 1 g dose (n=11). Geriatric Patients Cefepime pharmacokinetics have been investigated in elderly (65 years of age and older) men (n=12) and women (n=12) whose mean (SD) creatinine clearance was 74. There appeared to be a decrease in cefepime total body clearance as a function of creatinine clearance. Therefore, dosage administration of cefepime in the elderly should be adjusted as appropriate if the patient’s creatinine clearance is 60 mL/min or less [see Dosage and Administration (2) Pediatric Patients Cefepime pharmacokinetics have been evaluated in pediatric patients from 2 months to 11 years of age following single and multiple doses on every 8 hours (n=29) and every 12 hours (n=13) schedules. Following a single intravenous dose, total body clearance and the steady-state volume of distribution averaged 3. 0) mL/min/kg and 0. 1) L/kg, respectively. The urinary recovery of unchanged cefepime was 60. 4)% of the administered dose, and the average renal clearance was 2. 1) mL/min/kg. There were no significant effects of age or gender (25 male vs. 17 female) on total body clearance or volume of distribution, corrected for body weight. No accumulation was seen when cefepime was given at 50 mg per kg every 12 hours (n=13), while C max 1/2 Mechanism of Action Cefepime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefepime has a broad spectrum of in vitro Antimicrobial Activity Cefepime has been shown to be active against most isolates of the following bacteria, both in vitro [see Indications and Usage (1) ]: Gram-negative bacteria Enterobacter Escherichia coli Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa Gram-positive bacteria Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes The following in vitro in vitro Gram-positive bacteria Staphylococcus epidermidis Staphylococcus saprophyticus Streptococcus agalactiae NOTE: Most isolates of enterococci, eg, Enterococcus faecalis Gram-negative bacteria Acinetobacter calcoaceticus lwoffii Citrobacter diversus Citrobacter freundii Enterobacter agglomerans Haemophilus influenzae Hafnia alvei Klebsiella oxytoca Moraxella catarrhalis Morganella morganii Proteus vulgaris Providencia rettgeri Providencia stuartii Serratia marcescens NOTE: Cefepime is inactive against many isolates of Stenotrophomonas Xanthomonas maltophilia Pseudomonas maltophilia Susceptibility Test Methods For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: http://www.

Cefepime Injection is a cephalosporin antibacterial indicated in the treatment of the following infections caused by susceptible isolates of the designated microorganisms: pneumonia ( 1. 5 To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefepime Injection and other antibacterial drugs, Cefepime Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. 6 Cefepime Injection is indicated for pneumonia (moderate to severe) caused by Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter Cefepime Injection as monotherapy is indicated for empiric treatment of febrile neutropenic patients. In patients at high risk for severe infection (including patients with a history of recent bone marrow transplantation, with hypotension at presentation, with an underlying hematologic malignancy, or with severe or prolonged neutropenia), antimicrobial monotherapy may not be appropriate. Insufficient data exist to support the efficacy of cefepime monotherapy in such patients [ see Clinical Studies (14) Cefepime Injection is indicated for uncomplicated and complicated urinary tract infections (including pyelonephritis) caused by Escherichia coli Klebsiella pneumoniae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Cefepime Injection is indicated for uncomplicated skin and skin structure infections caused by Staphylococcus aureus Streptococcus pyogenes Cefepime Injection is indicated for complicated intra-abdominal infections (used in combination with metronidazole) caused by Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter Bacteroides fragilis [see Clinical Studies (14) To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefepime Injection and other antibacterial drugs, Cefepime 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.

Recommended Dosage in Adults With Creatinine Clearance (CrCL) Greater Than 60 mL/min ( 2. 1 Site and Type of Infection (Adults) Dose (IV) Frequency Duration (Days) Moderate to Severe Pneumonia For Pseudomonas aeruginosa 2. 1 1-2 g Every 10 Empiric therapy for febrile neutropenic patients 2 g Every 7 Or until resolution of neutropenia ( 2. 1 Mild to Moderate Uncomplicated or Complicated Urinary Tract Infections 0. 5-1 g Every 7-10 Severe Uncomplicated or Complicated Urinary Tract Infections 2 g Every 10 Moderate to Severe Uncomplicated Skin and Skin Structure Infections 2 g Every 10 Complicated Intra-abdominal Infections (used in combination with metronidazole) 2 g Every 7-10 2. 4 The recommended adult dosages and routes of administration are outlined in Table 1 Table 1: Recommended Dosage Schedule for Cefepime Injection in Adult Patients with Creatinine Clearance (CrCL) Greater Than 60 mL/min Site and Type of Infection Dose Frequency Duration (days) Adults Moderate to Severe Pneumonia due to S. pneumoniae P. aeruginosa For Pseudomonas aeruginosa , K. pneumoniae, Enterobacter 1-2 g IV Every 8-12 hours 10 Empiric therapy for febrile neutropenic patients [see Indications and Usage (1) Clinical Studies (14) 2 g IV Every 8 hours 7 or until resolution of neutropenia. In patients whose fever resolves but who remain neutropenic for more than 7 days, the need for continued antimicrobial therapy should be re-evaluated frequently. Mild to Moderate Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E. pneumoniae, P. mirabilis 0. 5-1 g IV Every 12 hours 7-10 Severe Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E. pneumoniae 2 g IV Every 12 hours 10 Moderate to Severe Uncomplicated Skin and Skin Structure Infections due to S. pyogenes 2 g IV Every 12 hours 10 Complicated Intra-abdominal Infections (used in combination with metronidazole) caused by E. aeruginosa , K. pneumoniae, Enterobacter B. fragilis [see Clinical Studies (14) 2 g IV Every 8-12 hours 7-10 The maximum dose for pediatric patients should not exceed the recommended adult dose. The usual recommended dosage in pediatric patients up to 40 kg in weight for durations as given above for adults is: Cefepime Injection in Galaxy Container should be used only in pediatric patients who require the entire 1 or 2 g dose and not any fraction thereof. Adult Patients Adjust the dose of Cefepime Injection in patients with creatinine clearance less than or equal to 60 mL/min to compensate for the slower rate of renal elimination. In these patients, the recommended initial dose of Cefepime Injection should be the same as in patients with CrCL greater than 60 mL/min except in patients undergoing hemodialysis. The recommended doses of Cefepime Injection in patients with renal impairment are presented in Table 2 When only serum creatinine is available, the following formula (Cockcroft and Gault equation) 1 Males: Creatinine Clearance (mL/min) = Weight (kg) x (140 en dash age) 72 x serum creatinine (mg/dL) Females: 0. 85 x above value Table 2: Recommended Dosing Schedule for Cefepime Injection in Adult Patients With Creatinine Clearance Less Than or Equal to 60 mL/min Creatinine Clearance (mL/min) Recommended Maintenance Schedule Greater than 60 500 mg every 1 g every 2 g every 2 g every 30en dash60 500 mg every 1 g every 2 g every 2 g every 11en dash29 500 mg every 500 mg every 1 g every 2 g every Less than 11 250 mg every 250 mg every 500 mg every 1 g every Continuous 500 mg every 1 g every 2 g every 2 g every Hemodialysis On hemodialysis days, Cefepime Injection should be administered following hemodialysis. Whenever possible, Cefepime Injection should be administered at the same time each day. 1 g on day 1, then 500 mg every 24 hours thereafter 1 g every In patients undergoing Continuous Ambulatory Peritoneal Dialysis (CAPD), Cefepime Injection may be administered at the recommended doses at a dosage interval of every 48 hours (see Table 2 In patients undergoing hemodialysis, approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be removed during a 3-hour dialysis period. The dosage of Cefepime Injection for hemodialysis patients is 1 g on Day 1 followed by 500 mg every 24 hours for the treatment of all infections except febrile neutropenia, which is 1 g every 24 hours. Cefepime Injection should be administered at the same time each day and following the completion of hemodialysis on hemodialysis days (see Table 2 Pediatric Patients Data in pediatric patients with impaired renal function are not available; however, since cefepime pharmacokinetics are similar in adults and pediatric patients [see Clinical Pharmacology (12. 3) Table 1 Table 2 Cefepime Injection in Galaxy Container is for intravenous administration using sterile equipment after thawing to room temperature. Thawing of Plastic Container Thaw frozen container at room temperature 25°C (77°F) or under refrigeration 5°C (41°F). Do not force thaw by immersion in water baths or by microwave irradiation. [See How Supplied/Storage and Handling (16) Check for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired. Do not add supplementary medication. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Visually inspect the container. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, the container should be discarded. Caution: Do not use plastic containers in series connections. Preparation for intravenous administration. Cefepime Injection should be administered intravenously over approximately 30 minutes. Intermittent intravenous infusion with a Y-type administration set can be accomplished with compatible solutions. However, during infusion of Cefepime Injection, it is desirable to discontinue the other solution. Solutions of cefepime, like those of most beta-lactam antibacterial drugs, should not be added to solutions of ampicillin at a concentration greater than 40 mg per mL, and should not be added to metronidazole, vancomycin, gentamicin, tobramycin, netilmicin sulfate or aminophylline because of potential interaction. However, if concurrent therapy with cefepime is indicated, each of these antibacterials can be administered separately. As with other cephalosporins, the color of Cefepime Injection tend to darken depending on storage conditions; however, when stored as recommended, the product potency is not adversely affected.

The following adverse reactions are discussed in other sections of the labeling: [see Warnings and Precautions (5. 1) [see Warnings and Precautions (5. 2) Clostridioides difficile [see Warnings and Precautions (5. 3) 6. 1 To report SUSPECTED ADVERSE REACTIONS, contact Baxter at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www. gov/medwatch. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials using multiple doses of cefepime, 4137 patients were treated with the recommended dosages of cefepime (500 mg to 2 g intravenously every 12 hours). There were no deaths or permanent disabilities thought related to drug toxicity. Sixty‑four (1. 5%) patients discontinued medication due to adverse reactions. Thirty-three (51%) of these 64 patients who discontinued therapy did so because of rash. The percentage of cefepime-treated patients who discontinued study drug because of drug-related adverse reactions was similar at daily doses of 500 mg, 1 g, and 2 g every 12 hours (0. 1%, and 2%, respectively). However, the incidence of discontinuation due to rash increased with the higher recommended doses. The following adverse reactions ( Table 3 Table 3: Adverse Reactions in Cefepime Multiple-Dose Dosing Regimens Clinical Trials in North America INCIDENCE EQUAL TO OR GREATER THAN 1% Local adverse reactions (3%), including phlebitis (1. 3%), pain and/or inflammation (0. 6%) Local reactions, irrespective of relationship to cefepime in those patients who received intravenous infusion (n=3048). INCIDENCE LESS THAN 1% BUT GREATER THAN 0. 1% Colitis (including pseudomembranous colitis), diarrhea, erythema, fever, headache, nausea, oral moniliasis, pruritus, urticaria, vaginitis, vomiting, anemia At the higher dose of 2 g every 8 hours, the incidence of adverse reactions was higher among the 795 patients who received this dose of cefepime. They consisted of rash (4%), diarrhea (3%), nausea (2%), vomiting (1%), pruritus (1%), fever (1%), and headache (1%). The following ( Table 4 Table 4: Adverse Laboratory Changes in Cefepime Multiple-Dose Dosing Regimens Clinical Trials in North America INCIDENCE EQUAL TO OR GREATER THAN 1% Positive Coombs’ test (without hemolysis) (16. 2%); decreased phosphorus (2. 8%); increased Alanine Transaminase (ALT) (2. 8%), Aspartate Transaminase (AST) (2. 4%), eosinophils (1. 7%); abnormal PTT (1. 6%), Prothrombin Time (PT) (1. 4%) INCIDENCE LESS THAN 1% BUT GREATER THAN 0. 1% Increased alkaline phosphatase, Blood Urea Nitrogen (BUN), calcium, creatinine, phosphorus, potassium, total bilirubin; decreased calcium Hypocalcemia was more common among elderly patients. Clinical consequences from changes in either calcium or phosphorus were not reported. A similar safety profile was seen in clinical trials of pediatric patients. The following adverse reactions have been identified during post-approval use of Cefepime Injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In addition to the adverse reactions reported during North American clinical trials with cefepime, the following adverse reactions have been reported during worldwide postmarketing experience. Encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), aphasia, myoclonus, seizures, and nonconvulsive status epilepticus have been reported [see Warnings and Precautions (5. 2)] Anaphylaxis including anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis, and thrombocytopenia, have been reported. In addition to the adverse reactions listed above that have been observed in patients treated with cefepime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibacterial drugs: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, fall in prothrombin activity, hepatic dysfunction including cholestasis, and pancytopenia.

Cefepime Injection is contraindicated in patients who have shown immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibacterials, penicillins or other beta-lactam antibacterial drugs. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

5 Risk summary There are no cases of cefepime exposure during pregnancy reported from postmarketing experience or from clinical trials. Available data from published observational studies and case reports over several decades with cephalosporin use in pregnant women have not established drug-associated risks of major birth defects, miscarriage or adverse maternal or fetal outcomes (see Data Cefepime was not associated with adverse developmental outcomes in rats, mice, or rabbits when administered parenterally during the period of organogenesis. The doses used in these studies were 1. 6 times (rats), approximately equal to (mice) and 0. 3 times (rabbits) the maximum recommended clinical dose ( see Data) The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Human Data While available studies cannot definitively establish the absence of risk, published data from case-control studies and case reports over several decades have not identified an association with cephalosporin use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups. Animal data Cefepime was not embryocidal and did not cause fetal malformations when administered parenterally during the period of organogenesis to rats at doses up to 1000 mg/kg/day, to mice at doses up to 1200 mg/kg/day, or to rabbits at doses up to 100 mg/kg/day. These doses are 1. 6 times (rats), approximately equal to (mice), and 0. 3 times (rabbits) the maximum recommended clinical dose based on body surface area. Risk Summary Cefepime is present in human milk at low concentration (0. A nursing infant consuming approximately 1000 mL of human milk per day would receive approximately 0. 5 mg of cefepime per day. There is no information regarding effects of cefepime on milk production or on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for cefepime and any potential adverse effects on the breastfed child from cefepime or from the underlying maternal condition. The safety and effectiveness of cefepime in the treatment of uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, pneumonia, and as empiric therapy for febrile neutropenic patients have been established in the age groups 2 months up to 16 years. Use of Cefepime Injection in these age groups is supported by evidence from adequate and well-controlled studies of cefepime in adults with additional pharmacokinetic and safety data from pediatric trials [see Clinical Pharmacology (12) Safety and effectiveness in pediatric patients below the age of 2 months have not been established. There are insufficient clinical data to support the use of Cefepime Injection in pediatric patients under 2 months of age or for the treatment of serious infections in the pediatric population where the suspected or proven pathogen is Haemophilus influenzae Cefepime Injection in Galaxy Container should be used only in pediatric patients who require the entire 1 or 2 g dose and not any fraction thereof. Of the more than 6400 adults treated with cefepime in clinical studies, 35% were 65 years or older while 16% were 75 years or older. When geriatric patients received the usual recommended adult dose, clinical efficacy and safety were comparable to clinical efficacy and safety in nongeriatric adult patients. Serious adverse events have occurred in geriatric patients with renal impairment given unadjusted doses of cefepime, including life-threatening or fatal occurrences of the following: encephalopathy, myoclonus, and seizures [see Warnings and Precautions (5) Adverse Reactions (6) This drug 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 renal function should be monitored [see Clinical Pharmacology (12) Warnings and Precautions (5) Dosage and Administration (2) Adjust the dose of Cefepime Injection in patients with creatinine clearance less than or equal to 60 mL/min to compensate for the slower rate of renal elimination [see Dosage and Administration (2.

3 The administration of cefepime may result in a false-positive reaction for glucose in the urine with certain methods. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used [see Warning and Precautions (5. 5)] Renal function should be monitored carefully if high doses of aminoglycosides are to be administered with Cefepime Injection because of the increased potential of nephrotoxicity and ototoxicity of aminoglycoside antibacterial drugs. Nephrotoxicity has been reported following concomitant administration of other cephalosporins with potent diuretics such as furosemide.

OVERDOSAGE
Patients who receive an overdose should be carefully observed and given supportive treatment. In the presence of renal impairment, hemodialysis, not peritoneal dialysis, is recommended to aid in the removal of cefepime from the body. Accidental overdosing has occurred when large doses were given to patients with impaired renal function. Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and neuromuscular excitability [see Warnings and Precautions (5) Adverse Reactions (6) Dosage and Administration (2)
NONCLINICAL TOXICOLOGY
No animal carcinogenicity studies have been conducted with cefepime. In chromosomal aberration studies, cefepime was positive for clastogenicity in primary human lymphocytes, but negative in Chinese hamster ovary cells. In other in vitro in vivo
CLINICAL STUDIES
The safety and efficacy of empiric cefepime monotherapy of febrile neutropenic patients have been assessed in two multicenter, randomized trials, comparing cefepime monotherapy (at a dose of 2 g intravenously every 8 hours) to ceftazidime monotherapy (at a dose of 2 g intravenously every 8 hours). These studies comprised 317 evaluable patients. Table 8 Table 8: Demographics of Evaluable Patients (First Episodes Only) Cefepime Ceftazidime Total 164 153 Median age (yr) 56 (range, 18-82) 55 (range, 16-84) Male 86 (52%) 85 (56%) Female 78 (48%) 68 (44%) Leukemia 65 (40%) 52 (34%) Other hematologic malignancies 43 (26%) 36 (24%) Solid tumor 54 (33%) 56 (37%) Median ANC nadir (cells per microliter) 20 (range, 0-500) 20 (range, 0-500) Median duration of neutropenia (days) 6 (range, 0-39) 6 (range, 0-32) Indwelling venous catheter 97 (59%) 86 (56%) Prophylactic antibiotics 62 (38%) 64 (42%) Bone marrow graft 9 (5%) 7 (5%) SBP less than 90 mm Hg at entry 7 (4%) 2 (1%) ANC = absolute neutrophil count; SBP = systolic blood pressure Table 9 Table 9: Pooled Response Rates for Empiric Therapy of Febrile Neutropenic Patients % Response Cefepime Ceftazidime Outcome Measures (n = 164) (n = 153) Primary episode resolved with no treatment modification, no new febrile episodes or infection, and oral antibiotics allowed for completion of treatment 51 55 Primary episode resolved with no treatment modification, no new febrile episodes or infection, and no post-treatment oral antibiotics 34 39 Survival, any treatment modification allowed 93 97 Primary episode resolved with no treatment modification and oral antibiotics allowed for completion of treatment 62 67 Primary episode resolved with no treatment modification and no post-treatment oral antibiotics 46 51 Insufficient data exist to support the efficacy of cefepime monotherapy in patients at high risk for severe infection (including patients with a history of recent bone marrow transplantation, with hypotension at presentation, with an underlying hematologic malignancy, or with severe or prolonged neutropenia). No data are available in patients with septic shock. Patients hospitalized with complicated intra-abdominal infections participated in a randomized, double-blind, multicenter trial comparing the combination of cefepime (2 g every 12 hours) plus intravenous metronidazole (500 mg every 6 hours) versus imipenem/cilastatin (500 mg every 6 hours) for a maximum duration of 14 days of therapy. The study was designed to demonstrate equivalence of the two therapies. The primary analyses were conducted on the protocol-valid population, which consisted of those with a surgically confirmed complicated infection, at least one pathogen isolated pretreatment, at least 5 days of treatment, and a 4 to 6 week follow-up assessment for cured patients. Subjects in the imipenem/cilastatin arm had higher APACHE II scores at baseline. The treatment groups were otherwise generally comparable with regard to their pretreatment characteristics. The overall clinical cure rate among the protocol-valid patients was 81% (51 cured/63 evaluable patients) in the cefepime plus metronidazole group and 66% (62/94) in the imipenem/cilastatin group. The observed differences in efficacy may have been due to a greater proportion of patients with high APACHE II scores in the imipenem/cilastatin group.
REFERENCES
1. Nephron.

Baxter Healthcare Company

CEFEPIME- cefepime_injection, solution Product manual source documgent