THE RESEARCH OF UNDESIRABLE ADVERSE REACTIONS TO DRUGS FROM THE GROUP OF FLUOROQUINOLONES

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VI. RELEVANCE

Fluoroquinolones are a large group of antimicrobial drugs of the quinolone class. They are highly active synthetic chemotherapeutic agents with a broad spectrum of action, characterized by a high degree of penetration into tissues and cells and good pharmacokinetic properties, which ensure the maintenance of high concentrations of the drug at the site of infection. Today fluoroquinolones (PCs) are among the most widely used drugs in outpatient practice [1].

Fluoroquinolones, like other antibacterial drugs, can cause unwanted adverse reactions (ADRs) that are not detected in pre-registration clinical trials due to the limited number of experimental participants and are characterized by a low frequency [2]. With the introduction of drugs into widespread practice and, accordingly, their reception by people of different ages and with various concomitant pathologies, the detection of CPD with a low frequency becomes possible. This is facilitated by the work of pharmacovigilance authorities [3].

In 2020, in connection with the pandemic of the new coronavirus infection COVID-19, the use of fluoroquinolones in clinical practice has increased significantly. According to TASS, in the fall of 2020, sales of levofloxacin, one of the drugs in the PC group, increased 46 times compared to the fall of 2019. The demand for levofloxacin in 2020 increased by 4159% compared to the data for 2019. The increase in PC consumption contributed to an increase in the detection of unwanted adverse reactions.

VII. AIM

To assess the adverse side reactions that have arisen in patients when using fluoroquinolone drugs for pharmacotherapy.

VIII. MATERIALS AND METHODS

A retrospective analysis of notifications on the occurrence of CPD for the use of drugs from the group of fluoroquinolones in clinical practice (form "Notification of an adverse reaction or lack of therapeutic effect of a medicinal product" of Appendix No. 1 to "Order of Roszdravnadzor of 15.02.2017 N 1071 On approval of the Procedure for the implementation of pharmacovigilance") ... We analyzed 95 notifications sent by medical organizations of the Voronezh region to the Regional Center for Monitoring the Safety of Medicines (RCMBS) for 2018-2020. Statistical data processing was carried out using the Microsoft Excel 2010 computer program. Of interest were the data on the total number of CPD, CPD for antimicrobial drugs, CPD for drugs from the group of fluoroquinolones, the frequency of detection of certain CPD on PC and the type of adverse reaction.

IX. RESULTS

When analyzing the ratio of CPD to antimicrobial drugs (AMP) relative to the total number of CPD, it was revealed that every year more than half of the notifications are filled in due to adverse reactions to AMP (on average, 254 ± 3 notifications per year for CPD when taking AMP versus 403 ± 12 notifications per year for all medicinal products (MPs)) .At the same time, one eighth of all notifications were notifications to the CPD when using fluoroquinolones (from 13.23% in 2018 to 11.9% in 2020).

In total, from 821 medicinal products in 2018 to 742 medicinal products in 2020 were mentioned in the notifications. The mention of fluoroquinolone drugs averaged 4.41% over three years.

An important part of the work was the identification of the most frequent and most rare undesirable side reactions to the use of PC for the period from 2018 to 2020.The highest rates are observed among the hepatotoxic effect and skin allergic reactions - 29.47% each, followed by an adverse reaction in the form dyspeptic disorders - 14%. Nephrotoxic effect, angioedema and phlebitis at the injection site and have approximately the same indicators - from 4.22% to 5.26%. The following NPDs are found with the lowest frequency: bronchospasm, hemorrhagic rash, hypotension, neurotoxic effect, exacerbation of chronic pancreatitis, Lyell's syndrome and tendonitis.

When comparing the types of adverse reactions to PC, no significant differences were found. CPD type A (dose-dependent reaction) prevailed over CPD type B (dose-independent reaction): on average 18 CPD per year type A versus 13.5 CPD per year type B.

X. DISCUSSION

Thus, the CPD for antimicrobial drugs represents more than half of the CPD for all drugs, and an eighth of the CPD for all drugs is accounted for by adverse reactions when using PC. The most common NCDs when taking fluoroquinolones include hepatotoxic effect and allergic skin reactions, the least common are bronchospasm, hemorrhagic rashes, hypotension, neurotoxic effect, exacerbation of chronic pancreatitis, Lyell's syndrome and tendinitis. not essential.

XI. CONCLUSION

Fluoroquinolones are a group of antimicrobial drugs that are highly active synthetic chemotherapeutic agents with a wide spectrum of action. Nowadays, there is a steady increase in the use of PCs, especially in connection with the pandemic of the new coronavirus infection COVID-19. Undesirable side reactions not identified in pre-registration clinical trials are established by pharmacovigilance authorities using notifications of an undesirable reaction or lack of a therapeutic effect of a drug.

In order to identify undesirable adverse reactions to fluoroquinolone drugs, a retrospective analysis of the above notifications for 2018-2020 was carried out. It has been established that more than half of the total number of teaching staff are teaching staff at AMP. One-eighth of the total number of CPDs belongs to undesirable side reactions to PC. Hepatotoxic effect and allergic skin reactions are the most frequent NCDs when taking PC; bronchospasm, hemorrhagic rash, hypotension, neurotoxic effect, exacerbation of chronic pancreatitis, Lyell's syndrome and tendonitis are the least frequent adverse reactions to drugs from the fluoroquinolone group. CPR type A (dose-dependent response) prevails over dose-independent CPR when taking fluoroquinolones.

About the authors

Yulia V. Khodarina

Воронежский государственный медицинский университет

Author for correspondence.
Email: hodarina@list.ru
ORCID iD: 0000-0001-6513-7735
SPIN-code: 6314-6062
Russian Federation

Mariam M. Musaeva

Voronezh State Medical University named after N.N. Burdenko

Email: musaewa.majam@yandex.ru
ORCID iD: 0000-0002-1683-921X
SPIN-code: 5419-8706
Russian Federation

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