title: Valproic acid-carbapenem interaction: report of six cases and a review of the literature.
abstract: 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.
authors.affiliation: University of Colorado Denver School of Pharmacy, Denver, CO, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Tobin
authors.forename: Larry K
authors.initials: LK
authors.lastname: Golightly
authors.forename: Steven D
authors.initials: SD
authors.lastname: Kick
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jones
mesh_terms: 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*
chemical_list: D000927:Anticonvulsants; D018692:Antimanic Agents; D015780:Carbapenems; D014635:Valproic Acid