Cefepime (Cefepime Hydrochloride) - Side Effects and Adverse Reactions

Clinical Trials Experience

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 thought by the investigators to be possibly, probably, or almost certainly related to drug toxicity. Thirty-three (51%) of these sixty-four 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 (0.8%, 1.1%, and 2.0%, respectively).

However, the incidence of discontinuation due to rash increased with the higher recommended doses.

The following adverse reactions were thought to be probably related to cefepime during evaluation of the drug in clinical trials conducted in North America (n=3125 cefepime-treated patients).

Table 3: Adverse Clinical Reactions Cefepime Multiple-Dose Dosing Regimens Clinical Trials — North America

Incidence equal to or greater than 1%	Local reactionsLocal reactions, irrespective of relationship to cefepime in those patients who received intravenous infusion (n=3048). (3.0%), including phlebitis (1.3%), pain and/or inflammation (0.6%); rash (1.1%)
Incidence less than 1% but greater than 0.1%	Colitis (including pseudomembranous colitis), diarrhea, fever, headache, nausea, oral moniliasis, pruritus, urticaria, vaginitis, vomiting

At the higher dose of 2 g every 8 hours, the incidence of probably-related adverse reactions was higher among the 795 patients who received this dose of cefepime. Reactions included rash (4%), diarrhea (3%), nausea (2%), vomiting (1%), pruritus (1%), fever (1%), and headache (1%).

The following adverse laboratory changes, irrespective of relationship to therapy with cefepime, were seen during clinical trials conducted in North America.

Table 4: Adverse Laboratory Changes Cefepime Multiple-Dose Dosing Regimens Clinical Trials — North America

Incidence equal to or greater than 1%	Positive Coombs' test (without hemolysis) (16.2%); decreased phosphorus (2.8%); increased ALT/SGPT (2.8%), AST/SGOT (2.4%); eosinophils (1.7%); abnormal PTT (1.6%), PT (1.4%)
Incidence less than 1% but greater than 0.1%	Increased alkaline phosphatase, BUN, calcium, creatinine, phosphorus, potassium, total bilirubin; decreased calciumHypocalcemia was more common among elderly patients. Clinical consequences from changes in either calcium or phosphorus were not reported., hematocrit, neutrophils, platelets, WBC

Postmarketing Experience

The following adverse reactions have been reported during postapproval use of cefepime. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to readily estimate their frequency or establish a causal relationship to drug exposure.

Anaphylaxis (including anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis and thrombocytopenia) has been reported.

Encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and nonconvulsive status epilepticus have been reported. Although most cases occurred in patients with renal impairment who received doses of cefepime that exceeded the recommended dosage schedules, some cases of encephalopathy occurred in patients receiving an appropriate dosage adjustment for their degree of renal impairment.

Cephalosporin-class Adverse Reactions

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 antibiotics: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal impairment, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, hepatic impairment including cholestasis, and pancytopenia.