Valproic acid-carbapenem interaction: report of six cases and a review of the literature.
OBJECTIVE
To evaluate the drug interactions between valproic acid (VPA) and carbapenem antibiotics.


METHODS
The effects of concurrent use of VPA and carbapenem antibiotics were evaluated in a retrospective observational study of hospitalized adults. Patients receiving both VPA and a carbapenem with at least two plasma VPA concentrations serially measured prior to, during, and/or after this combined treatment were included.


RESULTS
Six critically ill VPA-treated patients were identified who concurrently received meropenem (n=4), imipenem (n=1), or ertapenem (n=1). As compared with values obtained while not receiving treatment with the carbapenem, mean plasma VPA trough concentrations decreased by 58% (from 51.7 [95% confidence interval {CI} 28.0-75.4] to 21.8 [95% CI 11.1-32.5] mg/L; p = 0.025). Estimated mean VPA clearance increased by 191% (from 0.0158 [95% CI 0.0041-0.0275] to 0.0302 [95% CI 0.0169-0.0591] L/h/kg; p = 0.007). All VPA concentrations measured during concurrent VPA-carbapenem treatment were below the lower boundary of the usual therapeutic range. Five patients (83%) experienced generalized seizures during concurrent VPA-carbapenem treatment, including two with no prior history of seizures or epilepsy.


CONCLUSIONS
All recipients showed evidence of a complex pharmacokinetic and pharmacodynamic drug interaction between VPA and a carbapenem. Concurrent use of these medications should be avoided.
Tobin
Jennifer K
JK
University of Colorado Denver School of Pharmacy, Denver, CO, USA.
Golightly
Larry K
LK
Kick
Steven D
SD
Jones
Michael A
MA
D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood*; D018692:Antimanic Agents / Q000009:adverse effects / Q000097:blood*; D015780:Carbapenems / Q000009:adverse effects / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D012640:Seizures / Q000139:chemically induced; D014635:Valproic Acid / Q000009:adverse effects / Q000097:blood*
D000927:Anticonvulsants; D018692:Antimanic Agents; D015780:Carbapenems; D014635:Valproic Acid