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. 2023 Nov 1;10(11):1775.
doi: 10.3390/children10111775.

Analysis of Adverse Drug Reactions in Pediatric Patients with Epilepsy: An Intensive Pharmacovigilance Study

Ernestina Hernández García  1   2 , Lizbeth Naranjo  3 , Luz Adriana Pichardo-Macías  4 , María Josefa Bernad Bernad  5 , Lucila Isabel Castro-Pastrana  6 , Matilde Ruíz García  7 , Tanya Alejandra García Bernal  8 , Jessica Lizbeth Mendoza Solís  9 , David Calderón Guzmán  10 , Luisa Díaz-García  11 , Julieta Griselda Mendoza-Torreblanca  10 , Juan Luis Chávez Pacheco  1
Affiliations

Analysis of Adverse Drug Reactions in Pediatric Patients with Epilepsy: An Intensive Pharmacovigilance Study

Ernestina Hernández García et al. Children (Basel). .

Abstract

Epilepsy is a chronic neurological disease characterized by the presence of spontaneous seizures, with a higher incidence in the pediatric population. Anti-seizure medication (ASM) may produce adverse drug reactions (ADRs) with an elevated frequency and a high severity. Thus, the objective of the present study was to analyze, through intensive pharmacovigilance over 112 months, the ADRs produced by valproic acid (VPA), oxcarbazepine (OXC), phenytoin (PHT), and levetiracetam (LEV), among others, administered to monotherapy or polytherapy for Mexican hospitalized pediatric epilepsy patients. A total of 1034 patients were interviewed; 315 met the inclusion criteria, 211 patients presented ADRs, and 104 did not. A total of 548 ASM-ADRs were identified, and VPA, LEV, and PHT were the main culprit drugs. The most frequent ADRs were drowsiness, irritability, and thrombocytopenia, and the main systems affected were hematologic, nervous, and dermatologic. LEV and OXC caused more nonsevere ADRs, and PHT caused more severe ADRs. The risk analysis showed an association between belonging to the younger groups and polytherapy with ADR presence and between polytherapy and malnutrition with severe ADRs. In addition, most of the severe ADRs were preventable, and most of the nonsevere ADRs were nonpreventable.

Keywords: adverse drug reactions; anti-seizure medication; epilepsy; generalized estimating equations; levetiracetam; logistic regression; phenytoin; risk factors; valproic acid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Number of adverse drug reactions due to antiepileptics (ASM-ADR) among pediatric patients with epilepsy.
Figure 2
Figure 2
Comparison of different causality degrees for each anti-seizure medication (ASM) that provoked adverse drug reactions (ADRs) in pediatric patients with epilepsy. There was a significant difference among the different causality degrees of ADRs provoked by valproic acid (VPA), levetiracetam (LEV), phenytoin (PHT), oxcarbazepine (OXC), and clonazepam (CZP). Goodness of fit chi-squared test. * p value < 0.05. Topiramate (TPM), carbamazepine (CBZ), clobazam (CLB), and gabapentin (GBP).
Figure 3
Figure 3
Comparison of the different severity degrees of adverse drug reactions (ADRs) caused by the main ASM administered to pediatric patients with epilepsy. There was a significant difference among the severity degrees of ADRs caused by valproic acid (VPA), levetiracetam (LEV), phenytoin (PHT), oxcarbazepine (OXC), topiramate (TPM), and clonazepam (CZP). Goodness of fit chi-squared test. * p value < 0.05. Carbamazepine (CBZ), clobazam (CLB), and gabapentin (GBP).
Figure 4
Figure 4
Comparison of the different seriousness degrees of adverse drug reactions (ADRs) caused by the main anti-seizure medication (ASM) administered to pediatric patients with epilepsy. There was a significant difference among the severity degrees of ADRs caused by levetiracetam (LEV), phenytoin (PHT), and clonazepam (CZP). Goodness of fit chi-squared test. * p value < 0.05. Valproic acid (VPA), oxcarbazepine (OXC), topiramate (TPM), carbamazepine (CBZ), clobazam (CLB), and gabapentin (GBP).
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