Document Detail


Valproic acid-carbapenem interaction: report of six cases and a review of the literature.
MedLine Citation:
PMID:  20408498     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: 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:
Jennifer K Tobin; Larry K Golightly; Steven D Kick; Michael A Jones
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Drug metabolism and drug interactions     Volume:  24     ISSN:  0792-5077     ISO Abbreviation:  Drug Metabol Drug Interact     Publication Date:  2009  
Date Detail:
Created Date:  2010-04-22     Completed Date:  2010-07-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8904736     Medline TA:  Drug Metabol Drug Interact     Country:  England    
Other Details:
Languages:  eng     Pagination:  153-82     Citation Subset:  IM    
Affiliation:
University of Colorado Denver School of Pharmacy, Denver, CO, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Anticonvulsants / adverse effects,  blood*
Antimanic Agents / adverse effects,  blood*
Carbapenems / adverse effects,  pharmacology*
Drug Interactions
Female
Humans
Male
Middle Aged
Recurrence
Retrospective Studies
Seizures / chemically induced
Valproic Acid / adverse effects,  blood*
Chemical
Reg. No./Substance:
0/Anticonvulsants; 0/Antimanic Agents; 0/Carbapenems; 99-66-1/Valproic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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