Warning against concomitant use of VPA-carbapenem ineffective: study

Simultaneous use of carbapenem and valproic acid (VPA) is not common, but the best practice advisory (BPA) that warns clinicians of an interaction between these two drugs leading to significant declines in VPA levels does not appear to work in 63 percent of instances, reveals a study.

Notably, reductions in VPA levels may result in serious consequences for patients who are being treated for seizure disorder and unknown implications for alternative indications.

The authors conducted a retrospective chart review on all patients who had concomitant prescription of a carbapenem and VPA at Hartford Hospital in Connecticut, US, over 1 year. They obtained data on the level of care, duration of concomitant therapy, indications, VPA levels during or surrounding overlap, documentation of the interaction, and therapeutic implications.

Carbapenem was administered to 591 patients and VPA to 645. The BPA fired 126 times in 24 patients, and 15 received concomitant prescription of these medications. Among those on concomitant use, eight (53 percent) received VPA for seizures, while the remaining patients (47 percent) received this drug for other indications.

Additionally, eight of nine VPA levels were subtherapeutic during carbapenem therapy. Polypharmacy was also observed in all patients on VPA for nonconvulsive indications.

“Reductions in VPA efficacy for any indication should be expected with concomitant carbapenem administration,” the authors said.

“Antibiotics other than carbapenems should be considered when coverage of multidrug resistant Gram-negative pathogens is required in patients whose VPA treatment cannot be interrupted or switched to a therapeutic alternative,” they added.