Medication Errors and Genetic Factors as Possible Causes of Therapeutic Failures and Adverse Drug Reactions in a Group of Colombian Epilepsy Patients

Introduction: Epilepsy is a serious health problem worldwide, and its global prevalence is around 1%. Despite the introduction of new antiepileptic drugs, still more than 30% of epilepsy patients have drug-resistant forms of the disease, which leads to a significant increase in the morbidity and mortality of epilepsy [1].

Objective: To assess the impact of pharmacogenetic factors and medication errors as possible causes of therapeutic failures (TFs) and adverse drug reactions (ADRs) in a group of Colombian epileptic patients.

Methods: This was a prospective cohort analytical observational study. We included 77 adult Colombian epileptic patients, from the Liga Central Contra la Epilepsia and Hospital Universitario Mayor, to evaluate the following genetic polymorphisms: CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), C3435T (rs1045642) and IVS5-91 G > A (rs3812718), and the association with treatment response. Patients were followed long enough to confirm the existence of drug-resistant epilepsy (DRE) according to the International League Against Epilepsy (ILAE) criteria or treatment response [2], and the occurrence of ADRs. TFs and ADR were systematically evaluated for preventability using the modified Schumock and Thornton criteria [3].

Results: 53.2% of the patients had DRE and 87% of them used phenytoin. There was no association between the genetic variants evaluated and DRE. An association was found between mutant alleles of CYP2C9 and neuro-ophthalmological ADR (p = 0.001). 78% of the patients presented at least one ADR, the most frequent being those that affected the central nervous system (57%). 30% of the ADRs were associated with the patient’s genetic factors and 69% of them were classified as preventable. 36.6% of the cases of TFs could be explained by drug interactions and lack of therapeutic monitoring, so in fact, they could correspond to cases of “pseudo resistance”.

Conclusion: The alleles *2 and *3 of CYP2C9 were significantly associated with neuro ophthalmological ADRs in a sample of Colombian epileptic patients. However, the genetic variants evaluated did not explain the lack of response to antiepileptic treatment, as medication errors were identified in more than thirty percent of TF cases and almost 70% of ADRs.

Discussion: It is possible that the ABCB1 and SCN1A genes not only play a role as pharmacogenes but as biomarkers of disease [4, 5]. It is essential to implement pharmacovigilance programs in epileptic patients in order to optimize the benefit-risk ratio of antiepileptic drugs [6].