The Frequency and Structure of Adverse Drug Reactions in the Pharmacotherapy of Epilepsy

Abstract

The problem of the safety of antiepileptic therapy due to the duration of treatment and the need for regular intake of antiepileptic drugs (AEDs) is extremely significant. Adverse reactions (ADRs) may outweigh any positive effect of therapy associated with seizure reduction. The purpose of the study: to analyze the frequency and structure of ADRs of AEDs. Materials and Methods: The work was carried out within the framework of comprehensive research on the topic No. 210-16 "Epidemiological, genetic and neurophysiological aspects of diseases of the nervous system (central, peripheral and vegetative) and preventive medicine" (registration number 0120.0807480). Results: The frequency of ADRs against the background of third-generation AEDs was not inferior to that against the background of receiving second-generation AEDs, while the structure of ADRs was different: third-generation AEDs had a higher incidence of ADRs from the central nervous system, including a worsening of the course of epilepsy. The ratio of the chances of valproic acid accumulation with the achievement of toxic concentration in the blood and the development of un-desirable side effects in poor metabolizers (carriers of the polymorphism of CYP2C9*2 or CYP2C9*3) the gene encoding the cytochrome P450 isoenzyme 2C9 of the liver is 5.94 and 4.27, respectively. Conclusion: A personalized approach to ensuring the safety of valproic acid preparations based on taking into account the carriage of polymorphisms of the CYP2C9 gene allows to reduce the incidence of ADRs in patients receiving valproic acid preparations from 59.28% to 10.78%. The introduction of a personalized approach to the administration of valproates to patients suffering from epilepsy in the Krasnoyarsk Territory did not lead to an increase in direct costs.