Can cefepime (Cefepime) cause seizures in patients with impaired renal function?

Cefepime Can Cause Seizures, Especially in Patients with Renal Impairment

Yes, cefepime can cause seizures, particularly in patients with impaired renal function, and requires careful dosing adjustment to prevent neurotoxicity. 1

Neurotoxicity Risk with Cefepime

Cefepime has a significant potential to cause neurotoxicity, including seizures, due to its high pro-convulsive activity compared to other beta-lactam antibiotics:

• Cefepime has a relative pro-convulsive activity of 160 (compared to penicillin G at 100), making it one of the most epileptogenic beta-lactams 2
• Only cefazolin (294) has higher pro-convulsive activity among commonly used beta-lactams 2
• Neurotoxicity can manifest as:
  • Seizures (convulsive and non-convulsive)
  • Encephalopathy
  • Myoclonus
  • Confusion
  • Status epilepticus (sometimes fatal)

Risk Factors for Cefepime-Induced Seizures

The primary risk factor for cefepime-induced neurotoxicity is renal impairment:

• Renal failure causes rapid and significant accumulation of cefepime 2
• Elderly patients are at higher risk due to age-related decline in renal function 1
• FDA label specifically warns about "serious adverse events in geriatric patients with renal impairment given unadjusted doses of cefepime, including life-threatening or fatal occurrences of encephalopathy, myoclonus, and seizures" 1

However, neurotoxicity can occur even with appropriate dosing:

• A literature review of 135 cases of cefepime neurotoxicity showed that 26% of cases occurred in patients appropriately dosed for their renal function 2
• Patients with brain disorders may be at increased risk even with normal renal function 3

Concentration-Toxicity Relationship

Specific plasma concentration thresholds have been identified for cefepime neurotoxicity:

• Trough concentrations above 22 mg/L (with discontinuous infusions) or steady-state concentrations above 35 mg/L (with continuous infusion) are associated with neurotoxicity in 50% of patients 2
• When the free drug concentration exceeds 8 times the MIC of the target bacteria, the risk of neurotoxicity significantly increases 2

Prevention of Cefepime-Induced Seizures

To prevent cefepime-induced seizures:

1. Assess renal function before initiating therapy 1
2. Adjust dosing in renal impairment - for patients with creatinine clearance ≤60 mL/min 1
3. Monitor renal function during therapy - especially in elderly patients 1
4. Consider therapeutic drug monitoring when available to maintain safe drug levels 2
5. Temporarily suspend cefepime administration in patients experiencing unexplained neurological manifestations 2

Management of Cefepime-Induced Seizures

If cefepime-induced seizures occur:

1. Discontinue cefepime immediately - neurotoxicity is reversible upon drug discontinuation 4
2. Consider hemodialysis in severe cases - hemodialysis, not peritoneal dialysis, is effective in removing cefepime 1
3. Provide supportive care including anticonvulsants if needed 4
4. Monitor for improvement - mental status typically begins to improve within 24 hours of discontinuation and returns to baseline within days 5

Important Caveats

• Cefepime-induced neurotoxicity can be easily overlooked or misdiagnosed as other neurological conditions 4
• Non-convulsive status epilepticus is a particularly concerning presentation that requires EEG for diagnosis 6
• Neurotoxicity can occur even in patients receiving renally-adjusted doses 5
• The risk-benefit balance of cefepime therapy should be carefully considered in patients with renal impairment or pre-existing neurological conditions

In conclusion, cefepime has a well-documented potential to cause seizures, especially in patients with impaired renal function. Proper dose adjustment, vigilant monitoring, and prompt recognition of early signs of neurotoxicity are essential to prevent this serious adverse effect.