Prescribing Cefepime HCl in the absence of 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. As with other antimicrobials, prolonged use of it may result in overgrowth of nonsusceptible microorganisms. Repeated evaluation of the patient's condition is essential. Should superinfection occur during therapy, appropriate measures should be taken. Many cephalosporins, including cefepime, have been associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment, or p.o. nutritional state, as well as patients receiving a protracted course of antimicrobial therapy. Prothrombin time should be monitored in patients at risk, and exogenous vitamin K administered as indicated. Positive direct Coombs' tests have been reported during treatment with Cefepime HCl. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs' testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognized that a positive Coombs' test may be due to the drug. It should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis. Arginine has been shown to alter glucose metabolism and elevate serum potassium transiently when administered at 33 times the amount provided by the maximum recommended human dose of Cefepime. The effect of lower doses is not presently known.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: No long-term animal carcinogenicity studies have been conducted with cefepime. A battery of in vivo and in vitro genetic toxicity tests, including the Ames Salmonella reverse mutation assay, CHO/HGPRT mammalian cell forward gene mutation assay, chromosomal aberration and sister chromatid exchange assays in human lymphocytes, CHO fibroblast clastogenesis assay, and cytogenetic and micronucleus assays in mice were conducted. The overall conclusion of these tests indicated no definitive evidence of genotoxic potential. No untoward effects on fertility or reproduction have been observed in rats, mice, and rabbits when cefepime is administered subcutaneously at 1 to 4 times the recommended maximum human dose calculated on a mg/m2 basis.
Use in children: 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 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. 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 HCl 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 type b.
Use in elderly: Of the more than 6400 adults treated with Cefepime HCl 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 insufficiency given unadjusted doses of cefepime, including life-threatening or fatal occurrences of the following: encephalopathy, myoclonus, and seizures. 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.