What is the frequency of ceftriaxone-induced seizures in patients with impaired renal function?

Frequency of Ceftriaxone-Induced Seizures in Patients with Impaired Renal Function

Ceftriaxone-induced seizures occur with low frequency in patients with impaired renal function, with ceftriaxone having a relative pro-convulsive activity of only 12 compared to penicillin G (100), but the risk increases significantly with drug accumulation in severe renal impairment. 1, 2

Risk Assessment and Incidence

Ceftriaxone has a relatively low seizure potential compared to other beta-lactam antibiotics:

• According to the French Society of Pharmacology and Therapeutics, ceftriaxone has a relative pro-convulsive activity of 12 (compared to penicillin G at 100) 1
• For comparison, cefazolin (294) and cefepime (160) have much higher seizure potential 1

In patients with renal impairment:

• Neurological adverse events primarily occur in the setting of drug accumulation
• The FDA label warns specifically about neurological outcomes including encephalopathy, seizures, myoclonus, and non-convulsive status epilepticus in patients with severe renal impairment who experience ceftriaxone overdosage 2
• In a 2021 French Pharmacovigilance Database study of 152 cases of serious CNS adverse events from ceftriaxone:
  • 49.3% exhibited convulsions, status epilepticus, or myoclonia
  • The median age was 74.5 years
  • Median creatinine clearance was 35 mL/min
  • Median time to onset was 4 days 3

Pharmacokinetic Considerations

Ceftriaxone has unique pharmacokinetic properties that affect its seizure risk in renal impairment:

• Unlike many other beta-lactams, ceftriaxone typically does not require dose adjustment for renal insufficiency at doses of 2 grams or less per day 4
• Ceftriaxone is not significantly eliminated during hemodialysis 4
• In overdosage situations, drug concentration would not be reduced by hemodialysis or peritoneal dialysis 2

Risk Factors for Ceftriaxone-Induced Seizures

The risk of seizures is higher in patients with:

• Severe renal impairment 2, 3
• Advanced age 3
• Pre-existing CNS conditions 5
• Excessive dosing relative to renal function 5
• Plasma concentrations exceeding toxicity thresholds 3

Monitoring and Prevention

To minimize the risk of seizures in patients with impaired renal function:

• Monitor for early neurological symptoms (confusion, encephalopathy, myoclonus) that may precede seizures 3
• Consider EEG monitoring in high-risk patients, as 74% of patients with CNS adverse events had abnormal EEGs 3
• Maintain appropriate dosing (generally ≤2g/day) in patients with renal impairment 4
• Discontinue ceftriaxone immediately if neurological symptoms develop 2, 6

Clinical Course and Outcomes

When seizures do occur:

• They are typically reversible upon drug discontinuation 6, 7
• Median duration of neurological symptoms is approximately 4.5 days after drug discontinuation 3
• Serious outcomes can occur: in the French database study, 7.9% of patients with CNS adverse events died, and 10.5% had life-threatening reactions 3

Practical Recommendations

• In patients with renal impairment, maintain vigilance for neurological symptoms during ceftriaxone therapy, especially after day 4 of treatment 3, 8
• Consider alternative beta-lactams with lower seizure potential (like cefotaxime with relative pro-convulsive activity of 8.8) in patients with severe renal impairment and history of seizures 1
• If ceftriaxone must be used in high-risk patients, consider therapeutic drug monitoring when available 5

While ceftriaxone generally has a favorable safety profile in renal impairment compared to many other beta-lactams, clinicians should remain vigilant for the potential development of neurological adverse events, particularly seizures, in this vulnerable population.