From the FDA Drug Label
Carbapenem Antibiotics A clinically significant reduction in serum valproic acid concentration has been reported in patients receiving carbapenem antibiotics (ertapenem, imipenem, meropenem) and may result in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations drop significantly or seizure control deteriorates
Carbapenems and valproate should not be used concomitantly unless closely monitored, as carbapenem antibiotics may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control 1.
- Monitor serum valproic acid concentrations frequently after initiating carbapenem therapy.
- Consider alternative antibacterial or anticonvulsant therapy if serum valproic acid concentrations drop significantly or seizure control deteriorates. This interaction is also supported by 1.
From the Research
Carbapenems should not be used concomitantly with valproate due to a significant drug interaction that can reduce valproate levels, potentially leading to loss of seizure control and decreased quality of life. This interaction occurs because carbapenems, including meropenem, imipenem, ertapenem, and doripenem, can decrease the serum concentration of valproate, leading to subtherapeutic levels and increased risk of seizures 2. The reduction in valproate concentrations can occur within 24 hours of starting the carbapenem and may persist for days after discontinuation 3.
Key Considerations
- The interaction between carbapenems and valproate can lead to a significant decrease in valproate levels, resulting in subtherapeutic concentrations and increased risk of seizures 4.
- Alternative antibiotics should be considered whenever possible to avoid this interaction and minimize the risk of decreased valproate levels and seizures 2.
- If a carbapenem is absolutely necessary for a patient on valproate, close monitoring of valproate levels is essential, and significantly increased valproate dosing may be required, though this may not fully overcome the interaction 5.
- Clinicians should be aware of the potential for reduced valproate concentrations and aggravation of seizures when using carbapenems concomitantly with valproate, and should consider temporary alternative antiepileptic therapy and adjust valproate dosing as needed 3.
Clinical Implications
- The use of carbapenems with valproate can have significant clinical implications, including decreased quality of life and increased risk of seizures and morbidity 4.
- Clinicians should prioritize the use of alternative antibiotics and closely monitor valproate levels to minimize the risk of decreased valproate levels and seizures 2.
- The interaction between carbapenems and valproate highlights the importance of careful consideration of potential drug interactions and close monitoring of patients on concomitant therapy 6.