A.V. Matveev1,2, A.E. Krasheninnikov1, E.A. Egorova2
1 — National Research Center for Pharmacovigilance, Moscow, Russian Federation;
2 — Crimean Federal University V.I. Vernadsky, Medical Academy. S. I. Georgievsky, Simferopol, Russian Federation

Drug use is inherently associated with adverse drug reactions (ADRs). According to WHO-ART, the Adverse reaction terminology (ART) developed by the World Health Organization (WHO), ADR is any harmful or unpleasant reaction resulting from an intervention associated with the use of a drug (MP). which can be dangerous with subsequent prescriptions of the drug and suggests preventive measures or specific treatment, and also makes it necessary to change the regimen and / or dose of the drug or to cancel it.

In the Rules of Good Pharmacovigilance Practices (GVP) of the Eurasian Economic Union, the term “adverse reaction” refers to an unintentional adverse reaction of the body associated with the use of a drug and suggesting at least a possible relationship with the use of a suspected drug. It is known that in terms of mortality, ADRs are second only to cardiovascular, oncological, bronchopulmonary diseases and injuries. Children belong to special categories of patients, in the appointment of which drugs require special attention and caution. According to various sources, the incidence of ADR in hospitalized children ranges from 0.6 to 16.8%; at the same time, the duration of hospitalization also increases — by 8.25%. It is much more difficult to assess the incidence of ADR in children in outpatient practice. The high risk of side effects of drugs in children is associated, first of all, with the peculiarities of the pharmacokinetic and pharmacodynamic processes in their body. Drugs can also specifically affect the sexual development and immune system of children, as well as their physical and mental development. Moreover, the manifestations of ADR in this category of patients may differ significantly from the manifestations of adverse reactions in adults.

Insufficient study of drugs before they enter the pharmaceutical market does not allow their use in pediatric practice and, as a result, sharply reduces the number of drugs allowed for use in children. The lack of pharmacokinetic studies in pediatrics explains the lack of pediatric dosage forms in many drugs, which leads to difficulties in dosing. A limited number of clinical trials of drugs with the participation of children leads to the fact that doctors prescribe drugs to children, not only in disregard of the information set forth in the officially approved instructions for the medical use of drugs, but also using unlicensed drugs. The frequency of drug use with violations of instructions for use (hereinafter «off-label» — from the English «off» — outside, «label» — label, instruction) in pediatrics varies from 18 to 60% of all prescriptions, and in newborns it reaches 90 %. At the same time, the frequency of reporting is not high, which complicates the standard operating procedures (SOPs) of pharmacovigilance, the formation of documents on pharmacovigilance and the master file. “Unlicensed drugs” are chemicals used as medicines; imported drugs approved for use in other countries; modifications of approved drugs. Unlicensed drugs are used most often in very low birth weight infants, in children with cancer and with primary and secondary immunodeficiencies (HIV). Improving the safety of drug use in pediatric practice is inseparable from the identification, registration and analysis of ADRs within the framework of good pharmacovigilance practice. The study of the causes, patterns of development, features, consequences and methods of prevention of ADR in children will improve the effectiveness and quality of pharmacotherapy.

In the Republic of Crimea for the period 2011–2016. of all registered ADRs, 25% occurred in children, and every third adverse reaction was recorded in children in the first year of life. The most common causes of ADR were antimicrobials, drugs that affect the respiratory system, and non-steroidal anti-inflammatory drugs. Allergic reactions were the main clinical manifestations of ADR. It should be noted that ignoring the officially approved instructions for medical use of the drug plays an important role in the development of ADR in childhood. This is superimposed on the lack of reporting on the use of off-label drugs, which complicates the standard operating procedures (SOP) of pharmacovigilance, the formation of documents on pharmacovigilance and the master file. The main off-label drugs are cephalosporins (often used in pediatrics). The analysis carried out within the framework of good pharmacovigilance practice also showed that the most common cases in pediatric practice are cases of irrational choice of doses, as well as violations of the frequency of administration of drugs. The spontaneous reporting method is the main effective tool for identifying and studying the structure of off-label drug prescriptions in children. It is obvious that further development and improvement of the pharmacovigilance system is necessary to improve the quality of pharmacotherapy in childhood.