warnings and cautions
5 WARNINGS AND PRECAUTIONS • Hypersensitivity Reactions: Cross-hypersensitivity among beta-lactam antibacterial drugs may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Cefepime for Injection occurs, discontinue the drug. ( 5.1 ) • Neurotoxicity: May occur especially in patients with renal impairment administered unadjusted doses. If neurotoxicity associated with Cefepime for Injection therapy occurs, discontinue the drug. ( 5.2 ) • Clostridioides difficile -Associated Diarrhea (CDAD): Evaluate if diarrhea occurs. ( 5.3 ) 5.1 Hypersensitivity Reactions Before therapy with Cefepime for Injection is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other beta-lactams. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterial drugs has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Cefepime for Injection occurs, discontinue the drug and institute appropriate supportive measures. 5.2 Neurotoxicity Serious adverse reactions have been reported including life-threatening or fatal occurrences of the following: encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), aphasia, myoclonus, seizures, and nonconvulsive status epilepticus [ see Adverse Reactions (6.2) ]. Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment. However, some cases of neurotoxicity occurred in patients receiving a dosage adjustment appropriate for their degree of renal impairment. In the majority of cases, symptoms of neurotoxicity were reversible and resolved after discontinuation of cefepime and/or after hemodialysis. If neurotoxicity associated with cefepime therapy occurs, discontinue cefepime and institute appropriate supportive measures. 5.3 Clostridioides difficile -Associated Diarrhea Clostridioides difficile -Associated Diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefepime for 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 antibacterial drug 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 drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. 5.4 Development of Drug-Resistant Bacteria Prescribing Cefepime for 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. As with other antimicrobials, prolonged use of Cefepime for Injection 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. 5.5 Drug/Laboratory Test Interactions Urinary Glucose The administration of cefepime may result in a false-positive reaction for glucose in the urine when using some methods (e.g. Clinitest™ tablets) [ see Drug Interactions (7.1) ] . Coombs’ Tests Positive direct Coombs’ tests have been reported during treatment with Cefepime for Injection. In patients who develop hemolytic anemia, discontinue the drug and institute appropriate therapy. Positive Coombs’ test may be observed in newborns whose mothers have received cephalosporin antibacterial drugs before parturition. Prothrombin Time Many cephalosporins, including cefepime, have been associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment, or poor 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.