Meropenem and Seizure Threshold

Yes, meropenem can lower the seizure threshold, though it has a lower pro-convulsive potential compared to other carbapenems such as imipenem. 1

Seizure Risk with Meropenem

Meropenem has a documented pro-convulsive activity, with a relative pro-convulsive activity of 16 compared to penicillin G (which has a reference value of 100) 1
In comparison, imipenem has a higher pro-convulsive activity (71), while other beta-lactams like cefepime (160) and cefazolin (294) have significantly higher seizure risk 1
The FDA label for meropenem specifically mentions seizures as a potential adverse effect, particularly in patients with renal impairment 2
In pediatric patients with meningitis, seizure activity rates during meropenem therapy were comparable to those receiving comparator agents (cefotaxime or ceftriaxone) 2

Renal failure is the main risk factor associated with neurological toxicity of beta-lactams, including meropenem, as it may cause rapid and significant accumulation of the drug 1
For meropenem, trough concentrations above 64 mg/L have been associated with neurotoxicity in 50% of patients 1
The FDA label indicates increased incidence of seizures in patients with moderately severe renal impairment (creatinine clearance 10 to 26 mL/min) 2
High plasma concentrations of meropenem, particularly when the free concentration exceeds eight times the MIC, may increase the risk of neurological disorders 1

Meropenem should be used with caution in patients with a history of seizures or with clinical factors that may increase the risk of seizures 1
When the free minimum concentration normalized to the MIC for Pseudomonas aeruginosa exceeds 8, significant deterioration of neurological status occurred in approximately two-thirds of ICU patients treated with meropenem 1
Therapeutic drug monitoring should be considered in patients experiencing unexplained neurological manifestations, with temporary suspension of meropenem administration if necessary 1
Unlike some other antibiotics (such as metronidazole) that are contraindicated in patients with seizure disorders, meropenem can be used with appropriate monitoring and dosing adjustments 3, 4

Co-administration of meropenem with valproic acid can result in reduced valproic acid concentrations, potentially increasing the risk of breakthrough seizures in patients on anti-epileptic therapy 2
If administration of meropenem is necessary in patients receiving valproic acid, supplemental anti-convulsant therapy should be considered 2
The mechanism of this interaction is thought to involve inhibition of the hydrolysis of valproic acid's glucuronide metabolite back to valproic acid 2

Meropenem has a more favorable seizure risk profile compared to imipenem, with structural differences that may be responsible for the lower potential for epileptogenic activity 5
Safety studies have shown that meropenem-related seizures in patients with infections other than meningitis occurred at a rate of only 0.08% 6
When dosed appropriately, meropenem may be used to treat serious infections in critically ill patients with CNS disorders with minimal seizure risk 7
Meropenem is well tolerated by the CNS in clinical studies, reflecting animal data that suggests a low propensity to cause seizures compared to other carbapenems 8