N.B. Lazareva1, E.V. Shikh1, E.V. Rebrova1, A.Yu. Ryazanova2
1 First Moscow State Medical University. THEM. Sechenov (Sechenovsky University), Moscow, Russian Federation
2 Volgograd State Medical University, Volgograd, Russian Federation
The rapid progress in the creation and use of a huge number of drugs (MP), on the one hand, makes it possible to increase the effectiveness of treatment, and on the other, it can cause significant harm to the health of patients due to the development of unwanted drug reactions. The latter should be carefully considered by good pharmacovigilance practice. Currently, polypharmacy as a result of iatrogeny is a serious health problem due to a decrease in the effectiveness of pharmacotherapy and the development of severe adverse drug reactions, as well as a significant increase in health care costs — both public and personal funds. Unlike geriatric practice, there are very few works devoted to pediatric polypharmacy. However, the data currently available make one think about the widespread occurrence of this phenomenon, especially among hospitalized patients.
POLYPRAGMASIA: DEFINITION AND FEATURES OF TERMINOLOGY
The term «polypharmacy» (polypragmasia, from the Greek poly — a lot, pragma — an object, thing; or in foreign literature — polypharmacy, from the Greek poly — a lot, pharmacy — medicine) first appeared in the medical literature more than 150 years ago. At that time, it was attributed exclusively to the multi-component prescriptions of the LP. In the catalog of natural science literature indexed by MeSH (Medical Subject Headings) of the US National Library of Medicine Medline, the term «polypharmacy» was included only in 1997, and since then it is often used in the literature with different meanings and definitions. Often, «polypharmacy» or polypharmacy «means the simultaneous administration of up to five or more drugs to the patient. In particular, in a systematic review by N. Masnoon et al. (2017) analyzed English-language articles on the problem of defining «polypharmacy» published in the period from 2000 to 2016. Out of 1,156 articles on this topic, 110 were included in the analysis. It was shown that in almost half of the works (46%), “polypharmacy” was understood as the purpose of exactly 5 drugs.
In the order of the Ministry of Health of the Russian Federation No. 575n of November 2, 2012 «On the approval of the procedure for the provision of medical care in the profile of» clinical pharmacology «in paragraph 6, it is prescribed that if it is necessary to simultaneously prescribe 5 drugs to a patient or> 10 names in course treatment ) the patient should be referred to a clinical pharmacologist as part of good pharmacovigilance practice. Taking into account the fact that polypharmacy often leads to drug-drug interactions and the development of an adverse side reaction, on the one hand, and also the fact that often the simultaneous administration of several drugs can be beneficial in terms of clinical efficacy, in our opinion, it is legitimate from the point of view of clinical pharmacology looks like the definition, proposed by D. Sychev et al., that polypharmacy should be defined as «simultaneous unjustified prescription of a large number of drugs.» We believe that this definition may be relevant in pediatric practice.
Polypharmacy is classified as valid and unfounded. With justified polypharmacy, several drugs are prescribed to achieve a therapeutic effect with constant monitoring of their effectiveness and safety. In case of unreasonable polypharmacy, drugs of different groups are used that can enter into drug-drug interactions and cause severe adverse drug reactions, which are not always taken into account by good pharmacovigilance practice; monitoring of pharmacological effects is not carried out, which is more common with self-medication. Some authors classify polypharmacy into small (simultaneous administration of 2–4 drugs), large (simultaneous administration of 5–9 drugs) and excessive (simultaneous administration of 10 drugs or more). Allocate «rational» polypharmacy, based on clinical evidence obtained in large pharmacoepidemiological studies. However, in this case, too, polypharmacy should be carefully monitored for safety by good pharmacovigilance practice due to the continuing high risk of adverse drug reactions. The same can be said for many chronic diseases in pediatrics.
However, there is insufficient evidence of safety for many combination therapy options, including those prescribed in clinical guidelines. It is known that for clinical trials of new drugs, it is sufficient to study their use as monotherapy. As a consequence, we are often unaware of the effect of combination therapy on disease course and prognosis. This uncertainty is further enhanced in pediatric practice, where there is a lack of research on the efficacy and safety of drug use, and good pharmacovigilance practice is not always followed. Despite the existing uncertainty about the safety of drugs in children, the consumption of drugs in pediatric practice is growing. Polypharmacy is the “norm” for hospitalized infants and children. In 2002, the United States passed the Best Pharmaceuticals for Children Act, the main goal of which is to reduce the number of medical errors, including those associated with the simultaneous administration of a large number of drugs to hospitalized children.
Despite the widespread problem, there is no single definition of polypharmacy in pediatric practice. When diagnosing polypharmacy, factors such as the amount and duration of drug intake, drug classes, drug availability, health status and clinical conditions are usually taken into account, which leads to different interpretations. Thus, H. Chen et al. When studying the use of psychotropic drugs in outpatient pediatric practice, polypharmacy meant the simultaneous use of 2 drugs, classifying polypharmacy by the duration of simultaneous drug use (more than 14, 30, 60 and 90 days). J. Feinstein et al., Analyzing insurance payments under the US state program Medicaid in outpatient pediatric practice, according to the number of prescribed drugs, they distinguished low polypharmacy (low polypharmacy, 2–5 drugs), medium (medium, 5–9) and high (high, more than 10), as well as the duration of the course of simultaneous administration of drugs, short-term (1–30 days) and long-term (more than 30 days) polypharmacy were distinguished.