BARCELONA — Meropenem appears to rapidly and significantly decrease serum levels of valproic acid and should be used with caution in patients who are taking the anticonvulsant, Dr. Celeste Dias reported in a poster at the annual congress of the European Society of Intensive Care Medicine.
“We strongly recommend that VPA [valproic acid] serum levels be closely monitored in these patients,” said Dr. Dias of Hospital S. Joao, Oporto, Portugal.
“In high-risk patients, electroencephalographic monitoring should be considered.”
Dr. Dias presented a case review of 12 patients aged 12–78 years who were admitted to the hospital's neurological critical care unit.
Upon admission, all were taking VPA, either for a chronic seizure disorder or for prevention of seizures resulting from an acute brain disorder or injury.
During their stay in the neurological unit, all the patients began meropenem for nosocomial infections with gram-negative bacteria.
Routine serum VPA levels showed a significant and almost immediate drop in anticonvulsant levels after meropenem was initiated.
Within 60 hours, VPA levels had decreased to 20 mg/L or less in all 12 patients.
By day 6, three patients had no measurable levels of VPA during at least one blood draw.
“These decreases happened despite the fact that we actually increased VPA dosing to the maximum dose,” Dr. Dias commented.
Patients were monitored with EEG and none developed acute seizures despite the drop in VPA levels.
However, Dr. Dias noted, four of the patients were also taking other anticonvulsants, including phenytoin, carbamazepine, and topiramate.
There are several possible mechanisms for this drug interaction, she said, including the inhibition of plasma protein binding and suppression of enterohepatic recirculation.
“Meropenem seems to inhibit the hydrolytic enzyme involved in the hydrolysis of VPA-glucuronide to VPA, which results in a decrease in plasma concentration of the active drug,” Dr. Dias commented.