Does meropenem lower the seizure threshold?

From the Guidelines

Meropenem can lower the seizure threshold, particularly at high doses, as evidenced by the recommendation to use high doses with caution due to the association with seizures. This is supported by the study published in Intensive Care Medicine in 2015 1, which notes that high doses of meropenem are associated with seizures. When prescribing meropenem, it is essential to:

• Use caution in patients with a history of seizures or brain lesions
• Adjust dosing in patients with renal impairment
• Monitor patients closely for signs of seizure activity, especially during the first few days of treatment
• Consider alternative antibiotics in high-risk patients if clinically appropriate The mechanism by which meropenem lowers the seizure threshold is thought to be related to its ability to inhibit GABA receptors in the brain, which can lead to neuronal hyperexcitability, although this specific mechanism is not mentioned in the provided study 1. It is crucial to weigh the benefits of meropenem against the potential risks, particularly in patients with a history of seizure disorders or other risk factors.

Key considerations for meropenem use include:

• Recommended dose: 2 g/8 h for patients with normal renal function, as outlined in the study 1
• Potential for seizures at high doses, highlighting the need for careful dose selection and monitoring
• Importance of adjusting dosing in patients with renal impairment to minimize the risk of adverse effects.

Overall, while meropenem is a valuable antibiotic for treating various infections, its potential to lower the seizure threshold, especially at high doses, necessitates careful patient selection, dose adjustment, and monitoring to ensure safe and effective use.

From the FDA Drug Label

5.3 Seizure Potential Seizures and other adverse CNS experiences have been reported during treatment with meropenem for injection. These experiences have occurred most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) or with bacterial meningitis and/or compromised renal function

Meropenem and Seizure Threshold:

• Meropenem may lower the seizure threshold in certain patients, particularly those with pre-existing CNS disorders or compromised renal function.
• The drug label recommends close adherence to the recommended dosage regimens, especially in patients with known factors that predispose to convulsive activity.
• Dosage adjustment is recommended in patients with advanced age and/or adult patients with creatinine clearance of 50 mL/min or less.
• If focal tremors, myoclonus, or seizures occur, evaluate neurologically, place on anti-convulsant therapy if not already instituted, and re-examine the dosage of meropenem to determine whether it should be decreased or discontinued 2.

From the Research

Meropenem and Seizure Threshold

• Meropenem has been reported to lower the seizure threshold in certain patients, particularly those with renal impairment or receiving high doses 3.
• A study published in 2020 reported a case of a 65-year-old female patient with end-stage renal disease who developed tonic-clonic convulsions after receiving meropenem at the recommended dose 3.
• Another study published in 2009 noted that carbapenem antibiotics, including meropenem, are associated with a higher risk of seizures, particularly in patients with lower body weight, elderly, or those with impaired renal function 4.
• However, the same study also suggested that when dosed appropriately, meropenem may be used to treat serious infections in critically ill patients with central nervous system disorders or injury with minimal seizure risk 4.

Pharmacokinetics and Pharmacodynamics

• Meropenem pharmacokinetics are affected by renal function, with significant interindividual variability in plasma and cerebrospinal fluid concentrations 5.
• A study published in 2022 found that high doses of meropenem (up to 8-10 g/day) may be required to achieve effective concentrations in cerebrospinal fluid, particularly for less susceptible organisms 5.
• Alternative dosing strategies, such as prolonged infusion or continuous infusion, may improve pharmacodynamic target attainment rates and clinical outcomes 6, 7.
• However, the evidence for these alternative dosing strategies is largely based on pharmacokinetic and pharmacodynamic simulations, and more clinical studies are needed to confirm their efficacy and safety 6, 7.

Clinical Implications

• Clinicians should be aware of the potential risk of seizures associated with meropenem, particularly in patients with renal impairment or receiving high doses 3, 4.
• Dosing regimens for meropenem should be individualized based on patient factors, such as renal function and body weight, to minimize the risk of adverse effects and optimize pharmacodynamic target attainment rates 5, 6, 7.
• Further studies are needed to fully understand the relationship between meropenem and seizure threshold, as well as the optimal dosing strategies for this antibiotic 3, 5, 4, 6, 7.