Pharmacological interaction between valproic acid and carbapenem: What about levels in pediatrics?

Herrero, Ma Concepción Miranda; Romero, Andrés J. Alcaraz; Vilaplana, Vicente Escudero; Lafever, S.N. Fernández; Fernández-Llamazares, Cecilia M.; Barredo-Valderrama, Estíbaliz; Vázquez-López, M; Castro, Pedro de

doi:10.1016/j.ejpn.2014.12.010

Cited by 23 publications

(8 citation statements)

References 23 publications

(5 reference statements)

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“…The interaction between carbapenems and VPA may result in a significant decrease in serum VPA concentrations. The concomitant use of meropenem and VPA caused a 78% reduction in VPA concentrations in our patients, and 77% in the pooled analysis of the results from the literature [8,14–16,18–25,30]. The reduction of VPA concentrations occurred within 24–48 hours after the initiation of treatment with carbapenems.…”

Section: Discussionmentioning

confidence: 50%

“…In the VPA and ertapenem group, 19 patients from this study and 11 patients from seven reports [9,13,14,24,25,27,28] in the literature were included in the analysis reported in Table 2. The analysis of the VPA–ertapenem drug interaction showed a mean reduction of 71% (range, 38–98%) of VPA co‐concentrations.…”

Section: Resultsmentioning

confidence: 99%

“…In the meropenem group, the total analysis of 185 cases included 31 events from 13 case reports [8,14,18–24], 124 patients from four serial studies [15,16,25,26], and 30 patients from this study (Table 2). The VPA–meropenem drug interaction analysis showed a mean reduction of 77% (range, 34–99%) in VPA concentrations.…”

Section: Resultsmentioning

confidence: 99%

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Drug interaction between valproic acid and carbapenems in patients with epileptic seizures

Huang

Lin

Hsiao

et al. 2017

The Kaohsiung J of Med Scie

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Valproic acid (VPA) is a widely used antiepileptic drug (AED). When carbapenems are concomitantly used with VPA, the serum levels of VPA may decrease and aggravate seizures. The aim of this study was to evaluate the risk factors associated with decreased serum VPA levels and clinical outcome in patients being treated with a combination of carbapenems and VPA. Fifty-four adult patients who were treated with VPA for epileptic seizures concomitant with carbapenems for the treatment of infections were evaluated in this study. Serum VPA levels were measured before and during combination therapy with VPA and carbapenems, and the change in serum VPA levels was calculated. The risk factors related to the decrease in serum VPA levels and clinical outcomes were evaluated. Our results show that VPA concentrations were reduced to subtherapeutic levels after the introduction of carbapenems. The reduction in VPA concentrations was found within 24 hours of the start of treatment with carbapenems. VPA levels continuously declined while the combination of treatments was used, which aggravated epileptic seizures in 48% of the patients. Renal disease and enzyme-inducing AEDs were risk factors that contributed to the severity of reduced serum VPA levels during combined treatment with carbapenems. This study suggests that clinicians need to be aware of the reduction of VPA concentrations to subtherapeutic levels and the aggravation of seizures while patients are treated with a combination of carbapenems and VPA.

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Section: Discussionmentioning

confidence: 50%

Section: Resultsmentioning

confidence: 99%

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Drug interaction between valproic acid and carbapenems in patients with epileptic seizures

Huang

Lin

Hsiao

et al. 2017

The Kaohsiung J of Med Scie

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“…Таким образом, следует избегать одновременного использования препа-ратов этих классов, если это возможно [41]. Если избежать совместного назначения карбапенемов и вальпроата невозможно, следует контролировать концентрацию вальпроата в плазме [7,16,21].…”

Section: Ch I Ld Neurology R U S S I a N J O U R N A L O Funclassified

Overview of anticonvulsant therapy in full-term and premature neonates

Ивжиц

Зырянов

Родоман

et al. 2020

Rus. ž. det. nevrol.

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Convulsions in full-term and especially in premature newborns are observable pathologies. Selection of anticonvulsant therapy is very difficult: newborns have particular pharmacokinetics of drugs, insufficient data on doses and therapeutic concentrations of anticonvulsants in the blood (premature infants mainly). This article is an overview, with an emphasis on the features of dosing and pharmacokinetics of anticonvulsants in term and preterm infants.

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“…The drug interaction was classified 2 as probable (score 6), according to Drug Interaction Probability scale due to well documented evidence on adults 3 and a single study in children. 4 Carbapenems can irreversibly inhibit acylpeptide hydrolase, an enzyme that deconjugates valproate–glucuronide complex and reduces urinary elimination of VPA. 5 The abrupt onset 3 , 4 , 5 (<24 h), the slow 3 , 4 , 5 (7–20 days) time to return to therapeutic levels, and the risks associated with uncontrolled convulsions suggest to consider, when feasible, non-carbapenemic antibiotics in CP children on VPA.…”

mentioning

confidence: 99%