Can meropenem be given to a patient with a history of seizures?

Meropenem Use in Patients with Seizure History

Meropenem can be given to patients with a history of seizures, but requires careful risk assessment, dose adjustment for renal function, continuation of anticonvulsant therapy, and avoidance of concomitant valproic acid use. 1

Key Safety Considerations from FDA Labeling

Seizure Risk Profile

• Seizures and adverse CNS events have been reported with meropenem, occurring most commonly in patients with CNS disorders (including history of seizures), bacterial meningitis, or compromised renal function 1
• In clinical trials of 2,904 immunocompetent adults treated for non-CNS infections, the overall seizure rate was 0.7% (20 patients), and all patients who developed seizures had pre-existing contributing factors including prior seizure history or CNS abnormalities 1
• In patients with infections other than meningitis, the incidence of drug-related seizures was only 0.08% 2

Critical Management Requirements

Anticonvulsant Continuation:

• Continue anti-convulsant therapy in patients with known seizure disorders throughout meropenem treatment 1
• If focal tremors, myoclonus, or seizures occur during treatment, perform neurological evaluation, initiate or optimize anticonvulsant therapy, and reassess meropenem dosage for potential reduction or discontinuation 1

Dose Adjustment:

• Dosage adjustment is mandatory in patients with creatinine clearance ≤50 mL/min, as renal impairment is the primary risk factor for meropenem-induced neurotoxicity 1
• Close adherence to recommended dosing regimens is essential, especially in patients with factors predisposing to convulsive activity 1

Critical Drug Interaction: Valproic Acid

The Carbapenem-Valproate Interaction

The concomitant use of meropenem and valproic acid or divalproex sodium is generally not recommended 1

Mechanism and Clinical Impact:

• Co-administration of carbapenems including meropenem causes rapid reduction in valproic acid concentrations, dropping levels below the therapeutic range 1, 3, 4
• This interaction significantly increases the risk of breakthrough seizures 1, 3, 4
• Increasing valproic acid dosage may not be sufficient to overcome this interaction 1

Clinical Evidence:

• A case report documented an 85-year-old patient who experienced rapid declines in valproic acid concentrations on two separate occasions when meropenem was administered, with seizures occurring during the second treatment period despite previous tolerance 3
• Another case described a 55-year-old woman with 16 years of seizure control on valproic acid who developed breakthrough seizures within 5 days of meropenem initiation; seizures resolved and valproic acid levels normalized after meropenem discontinuation 4

Management Algorithm for Valproic Acid Patients

Preferred Approach:

• Consider alternative antibacterial agents (non-carbapenems) to treat infections in patients whose seizures are well-controlled on valproic acid or divalproex sodium 1

If Meropenem is Necessary:

• Consider supplemental anticonvulsant therapy beyond valproic acid 1
• Implement very close serum valproic acid concentration monitoring 3
• Maintain intensive clinical observation for seizure activity 3
• Be aware that the interaction effect is unpredictable, even in patients who previously tolerated the combination 3

Comparative Safety with Other Beta-Lactams

Meropenem has favorable CNS tolerability compared to other carbapenems:

• Meropenem is well tolerated by the CNS with seizures reported infrequently, allowing use at high doses and in patients with meningitis 5
• The incidence of seizures with meropenem is low even in meningitis patients, with no drug-related seizures reported in this population in clinical trials 2
• Meropenem has demonstrated a favorable safety profile across nearly 5,000 patients in clinical trials 2

Special Populations

Pediatric Patients:

• Meropenem is particularly useful in bacterial meningitis treatment in children, with low seizure incidence despite CNS penetration 6
• The drug has demonstrated high efficacy and safety in children aged 1 month to 12 years with various severe infections 6

Elderly Patients:

• Exercise particular caution in elderly patients with CNS disorders, as they may be at higher risk for drug interactions and adverse effects 3
• Ensure appropriate dose adjustment for age-related decline in renal function 1

Common Pitfalls to Avoid

• Failing to adjust dose for renal impairment, which is the primary risk factor for beta-lactam neurotoxicity 1
• Continuing valproic acid without considering alternative anticonvulsants when meropenem is clinically necessary 1
• Discontinuing baseline anticonvulsant therapy during meropenem treatment 1
• Assuming prior tolerance predicts future safety when re-challenging with meropenem-valproate combination 3