What are the precautions and considerations when using cefepime in patients with impaired renal function or underlying neurological conditions?

From the Guidelines

Cefepime can reduce the seizure threshold, particularly in patients with impaired renal function or underlying neurological conditions, and therefore requires careful dose adjustment and monitoring to prevent neurotoxicity. The risk of neurotoxicity, including seizures, is higher in patients with renal failure, as cefepime can accumulate rapidly and significantly in these patients 1. A literature review of 37 studies on cefepime neurotoxicity found that 48% of cases occurred in patients who were overexposed to the drug, highlighting the importance of appropriate dosing based on renal function 1.

Key Considerations for Cefepime Use

• Patients with creatinine clearance 30-60 mL/min should receive reduced doses of 1-2g every 24 hours
• Patients with clearance 11-29 mL/min should receive 1g every 24 hours
• Patients with clearance ≤10 mL/min should receive 0.5-1g every 24 hours
• Hemodialysis patients require a supplemental dose after dialysis sessions
• Patients with underlying neurological conditions require careful monitoring for signs of neurotoxicity, such as encephalopathy, myoclonus, seizures, or non-convulsive status epilepticus

Monitoring and Management

• Regular neurological assessments and therapeutic drug monitoring are recommended, especially in elderly patients with reduced renal function
• If neurological symptoms develop, consider discontinuing cefepime and switching to an alternative antibiotic with less neurotoxic potential
• Symptoms typically resolve within 2-7 days after discontinuation, though temporary anticonvulsant therapy may be needed in severe cases
• Cefepime trough concentrations above 22 mg/L (when administered by discontinuous infusions) or concentrations at steady state above 35 mg/L (when administered by continuous infusion) have been associated with neurotoxicity in 50% of patients 1

From the FDA Drug Label

5.2 Neurotoxicity (No specific information about reducing seizure threshold is provided in this section, but it does mention neurotoxicity)

The FDA drug label does not answer the question.

From the Research

Cefepime and Seizure Threshold

• Cefepime has been associated with neurotoxicity, including seizures, particularly in patients with renal impairment or underlying neurological conditions 2, 3, 4, 5, 6.
• The mechanism of cefepime-induced neurotoxicity is thought to be related to its ability to cross the blood-brain barrier and exhibit concentration-dependent γ-aminobutyric acid (GABA) antagonism 2.
• Risk factors for cefepime-induced neurotoxicity include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations 2, 3, 6.

Precautions and Considerations

• Patients with impaired renal function or underlying neurological conditions should be closely monitored for signs of neurotoxicity when receiving cefepime 2, 3, 4, 5, 6.
• Dose adjustments should be made in patients with renal impairment to avoid excessive cefepime concentrations 3, 6.
• Cefepime-induced neurotoxicity can occur despite appropriate dosing, and clinicians should be aware of the potential for this adverse reaction 2, 3, 4, 5, 6.

Clinical Presentation and Management

• Cefepime-induced neurotoxicity can present with a range of symptoms, including altered mental status, myoclonus, seizures, and coma 2, 3, 4, 5, 6.
• Management of cefepime-induced neurotoxicity typically involves discontinuation of the drug, administration of antiepileptic medications, and hemodialysis in severe cases 2, 3, 4, 6.