Drug-drug interaction between valproic acid and meropenem: a retrospective analysis of electronic medical records from neurosurgery inpatients

Wen, Zhi Peng; Fan, Shuang Shi; Du, Can; Yin, Tongming; Zhou, Boting; Peng, Ze Feng; Xie, Yuan Yang; Zhang, W.; Chen, Y.; Xiao, Jian; Chen, X.-P.

doi:10.1111/jcpt.12501

Cited by 22 publications

(22 citation statements)

References 54 publications

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“…There are few case reports describing decreased VPA serum levels by carbapenems (Nacarkucuk et al, 2004;Clause et al, 2005;Fudio et al, 2006;Suntimaleeworakul et al, 2012). A recent study also documented the decreased VPA levels caused by concomitant use of meropenem using a large number of therapeutic drug monitoring (TDM) records (Wen et al, 2017). We present additional two cases of this significant drug interaction.…”

Section: Introductionmentioning

confidence: 73%

Meropenem-induced Valproic Acid Elimination: A Case Report of Clinically Relevant Drug Interaction

et al. 2017

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We present two case reports of drug interaction between valproic acid and meropenem. In comparison with expected population-kinetic based serum levels, we observed 90.8 and 93.5% decrease in valproic acid serum levels during concomitant administration with meropenem. If carbapenems need to be administered to valproic acid treated patient, other anticonvulsant addition seems to be the appropriate as most probably the valproic acid dose escalation would not be sufficient to achieve therapeutic serum concentration.

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Section: Introductionmentioning

confidence: 73%

Meropenem-induced Valproic Acid Elimination: A Case Report of Clinically Relevant Drug Interaction

et al. 2017

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“…One additional serious interaction to consider as the incidence of multidrug-resistant organisms increases is between carbapenem antibiotics and valproic acid. Numerous potential mechanisms exist to describe this interaction; however, it is believed that carbapanems inhibit an enzyme crucial to the production of the pharmacologically active moiety of valproic acid, resulting in significantly reduced plasma valproic acid concentrations [83,84,85]. In patients on valproic acid, alternatives to carbapenems should be utilized if possible.…”

Section: Special Considerationsmentioning

confidence: 99%

Prevention, Treatment, and Monitoring of Seizures in the Intensive Care Unit

Strein

Holton-Burke

Smith

et al. 2019

JCM

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The diagnosis and management of seizures in the critically ill patient can sometimes present a unique challenge for practitioners due to lack of exposure and complex patient comorbidities. The reported incidence varies between 8% and 34% of critically ill patients, with many patients often showing no overt clinical signs of seizures. Outcomes in patients with unidentified seizure activity tend to be poor, and mortality significantly increases in those who have seizure activity longer than 30 min. Prompt diagnosis and provision of medical therapy are crucial in order to attain successful seizure termination and prevent poor outcomes. In this article, we review the epidemiology and pathophysiology of seizures in the critically ill, various seizure monitoring modalities, and recommended medical therapy.

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“…Meropenem has been shown to have a favourable safety profile, especially in central nervous system (CNS) tolerability. Therefore, for neurosurgical patients with active seizure disorder, or those who are at a high risk of developing seizures, meropenem is preferred when carbapenem antibiotics are indicated (3). However, a series of reports have indicated that the concomitant use of VPA and carbapenems, especially meropenem, can rapidly reduce the VPA plasma concentration (1,(3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, for neurosurgical patients with active seizure disorder, or those who are at a high risk of developing seizures, meropenem is preferred when carbapenem antibiotics are indicated (3). However, a series of reports have indicated that the concomitant use of VPA and carbapenems, especially meropenem, can rapidly reduce the VPA plasma concentration (1,(3)(4)(5)(6)(7)(8). In our hospital, pharmacists found that the concomitant use of VPA and carbapenems was not completely avoided, and was accompanied decreased VPA concentration as well as a significantly higher alanine aminotransferase (ALT) value.…”

Section: Introductionmentioning

confidence: 99%

Interaction between valproic acid and carbapenems: decreased plasma concentration of valproic acid and liver injury

Li¹,

Gao²,

Liu³

et al. 2021

Ann Palliat Med

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Background: Several case reports and retrospective studies have indicated that carbapenems decrease the plasma concentration of valproic acid (VPA). This retrospective study examines the effect of carbapenems on VPA levels, and explores whether the drug-drug interaction can influence the liver function of patients.Methods: The data of 141 patients were collected from the Department of Neurosurgery at Shanxi Bethune Hospital from January 2018 to December 2019. We compared the VPA levels between the VPA monotherapy group and VPA + carbapenem group to evaluate the influence of carbapenem antibiotics on the plasma concentration of VPA. We also compared the liver injury rate of the VPA monotherapy group, VPA + meropenem group, and VPA + imipenem group to evaluate the influence of concomitant use of VPA with carbapenem antibiotics on liver function. Results:The VPA serum concentration in the VPA + meropenem group was 22.32±21.77 µg/mL, which was markedly lower than that in the VPA monotherapy group (i.e., without carbapenems) (65.17±21.49 µg/mL) (P<0.01). The rate of liver injury was significantly different between the VPA monotherapy, VPA + meropenem, and VPA + imipenem groups (χ 2 =30.13, P<0.01). Further comparisons showed that the liver injury rate of the VPA + meropenem group (35.42%) was higher than that of the VPA + imipenem (3.7%) and VPA monotherapy (1.52%) groups (P<0.01). Although no significant differences in liver injury rate were observed between the VPA + imipenem (3.7%) and VPA monotherapy (1.52%) groups, the alanine aminotransferase (ALT) value of the VPA + imipenem group after co-administration (65.22±48.01 U/L) was notably higher than before (40.48±24.97 U/L) (P<0.01). Conclusions:In this study, the interaction between VPA and carbapenems resulted in decreased plasma concentrations of VPA as well as possible liver injury. Clinicians should be aware of this potential interaction, and closely monitor VPA concentrations and liver function. Different carbapenems combined with VPA showed different effects on both VPA concentration and liver function, indicating that the mechanisms of these two effects might be related.

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Drug-drug interaction between valproic acid and meropenem: a retrospective analysis of electronic medical records from neurosurgery inpatients

Cited by 22 publications

References 54 publications

Meropenem-induced Valproic Acid Elimination: A Case Report of Clinically Relevant Drug Interaction

Meropenem-induced Valproic Acid Elimination: A Case Report of Clinically Relevant Drug Interaction

Prevention, Treatment, and Monitoring of Seizures in the Intensive Care Unit

Interaction between valproic acid and carbapenems: decreased plasma concentration of valproic acid and liver injury

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