Analysis of the valproic acid-meropenem interaction in hospitalised patients

Vélez-Díaz-Pallarés, Manuel; Silveira, Eva Delgado; Díaz, Ana María Álvarez; Menéndez-Conde, C. Pérez; Oliveros, Noelia Vicente; Vicedo, T. Bermejo

doi:10.1016/j.nrleng.2011.03.006

Cited by 13 publications

(16 citation statements)

References 19 publications

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“…doripenem (Hellwig et al, 2011), ertapenem (Lunde et al, 2007), and meropenem (Llinares Tello et al, 2003;Coves-Orts et al, 2005;Fudio et al, 2006;Taha et al, 2013) with VPA is associated with a clinically significant decrease in the plasma concentrations of VPA. A series of 26 patients with concomitant meropenem and VPA treatment supports the findings of these cases (Vélez Díaz-Pallarés et al, 2012). In the literature search we conducted, we could find only three previous publications reporting an interaction between imipenem and VPA (Llinares Tello et al, 2003;Fudio et al, 2006;Park et al, 2012).…”

Section: Discussionsupporting

confidence: 76%

“…The interaction was fully reversible within hours of discontinuing imipenem treatment. The effects of carbapenems on VPA concentrations seem to indicate a class effect (Mancl and Gidal, 2009), and the magnitude of the effects seem to be equal among various carbapenems; the decrease in VPA concentrations has been in the range of 50 to 96% (Llinares Tello et al, 2003;Coves-Orts et al, 2005;Hellwig et al, 2011;Lunde et al, 2007;Park et al, 2012;Taha et al, 2013;Perea et al, 2006;Vélez Díaz-Pallarés et al, 2012). The interaction has been observed when VPA has been administered either enterally (Park et al, 2002;Llinares Tello et al, 2003;Fudio et al, 2006;Taha et al, 2013) or intravenously (Coves-Orts et al, 2005;Lunde et al, 2007;Hellwig et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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Concomitant treatment with imipenem causes a rapid and extensive decrease in the plasma concentrations of valproic acid

Keränen¹,

Kuusisto²

2016

Journal of Epileptology

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Background. Valproic acid (VPA) is a wide-spectrum antiepileptic drug used both in children and in adults. We describe a clinically important interaction between VPA and imipenem, a carbapenem antimicrobial. Case presentation. Our patient was a 19-year-old man with childhood onset of mental retardation and severe epilepsy. He was hospitalized due to pneumonia. His antiepileptic drugs, including VPA, were administered intravenously. Due to pneumonia, intravenously administered imipenem was started. After the start of imipenem treatment, a dramatic decrease in the plasma concentrations of VPA occurred within 24 hours. After the discontinuation of imipenem treatment, the concentration of VPA recovered within a few hours. The decrease in VPA levels was associated with increased seizure frequency. Conclusions. The time course of the VPA-imipenem interaction suggests that mechanisms other than a change in the enzymatic elimination of VPA is the cause for this pharmacokinetic interaction. Concomitant use of VPA and imipenem should be avoided.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Concomitant treatment with imipenem causes a rapid and extensive decrease in the plasma concentrations of valproic acid

Keränen¹,

Kuusisto²

2016

Journal of Epileptology

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“…A reduction in the concentration reached even 96% while, in many cases, a therapeutic concentration of valproic acid could not be obtained [95,96]. Since interactions resulted in seizures, simultaneous administration of carbapenems is contraindicated.…”

Section: Valproic Acidmentioning

confidence: 99%

Farmakokinetyczne interakcje międzylekowe w oddziale intensywnej terapii – obserwacje jednoośrodkowe i przegląd piśmiennictwa

Łój¹,

Olender²,

Ślęzak³

et al. 2014

Anaesthesiol Intensive Ther

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Background: Drug-drug interactions constitute a serious health hazard in everyday clinical practice in critically ill patients. Drug-drug interactions may be pharmacokinetic or pharmacodynamic in their nature. We aimed to investigate the quantity and quality of possible drug-drug interactions, and their possible side effects in intensive care unit patients in a 12-month period. Methods: This retrospective study covered data on pharmacological treatment of 43 consecutive patients (11 females, 32 males) aged 62 ± 15 years, hospitalized between January 2015 and February 2016. Pharmacokinetic DDIs were identified and graded. Only severe and clinically important drug-drug interactions were subjected for further analysis. Results: Median baseline SAPS III was 53 (IQR 38-67) points. Median intensive care unit stay was 12 (6-25) days. Subjects were treated with a median number of 22 (12-27) drugs. We identified 27 (16-41) possible drug-drug interactions per patient, including 3 (1-7) drug-drug interactions of a severe grade. The total number of severe and clinically important drug-drug interactions was 253 of which 227 were analyzed in detail. No possible side-effects of drug-drug interactions were identified. Conclusions: DDIs as well as their side-effects are challenging regarding their precise evaluation, especially due to the need for multidrug treatment in critically ill patients. Concentration-controlled therapy should be recommended, especially for treatment with vancomycin, digoxin and valproate. Pantoprazole should be a proton pump-inhibitor of choice. Drug dose modification is necessary in combined treatment with fluconazole and amiodarone or rifampicin. From a clinical point of view, the most important impact of drug-drug interactions is on antibiotic treatment effectiveness, especially with meropenem when valproate is also prescribed.

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“…The addition of the beta-lactam antibiotic meropenem (MER) for antimicrobial chemotherapy to an ongoing therapy with valproic acid (VPA) leads to a well-known decrease of VPA serum concentrations [1,2]. Largely unknown is the influence of this pharmacokinetic interaction on a concurrent treatment with the second generation antipsychotic risperidone (RIS).…”

Section: Case Reportmentioning

confidence: 99%