safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2020-8-3-109-122safetyrisk-190Research ArticleОБЗОРЫREVIEWSЛекарственно-индуцированные нейтропения и агранулоцитозDrug-Induced Neutropenia and Agranulocytosishttps://orcid.org/0000-0002-0795-8225ОстроумоваО. Д.OstroumovaO. D.

д-р мед. наук, профессор

ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

ул. Трубецкая, д. 8, стр. 2, Москва, 119991

 Dr. Sci. (Med.), Professor

2/1/1 Barrikadnaya St., Moscow 125993

8/2 Trubetskaya St., Moscow 119991

ostroumova.olga@mail.ruhttps://orcid.org/0000-0001-5801-3742КочетковА. И.KochetkovA. I.

канд. мед. наук

ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

Cand. Sci. (Med.)

2/1/1 Barrikadnaya St., Moscow 125993

ak_info@list.ruhttps://orcid.org/0000-0002-2923-6450ПавлееваЕ. Е.PavleevaE. E.

канд. мед. наук

ул. Делегатская, д. 20/1, Москва, 127423

Cand. Sci. (Med.)

20/1 Delegatskaya St., Moscow 127423

pavleeva.elena@mail.ruhttps://orcid.org/0000-0001-8551-1421КравченкоЕ. В.KravchenkoE. V.

ул. Делегатская, д. 20/1, Москва, 127423

20/1 Delegatskaya St., Moscow 127423

effetivo@icloud.comФедеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации; Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И. М. Сеченова» Министерства здравоохранения Российской ФедерацииРоссияRussian Medical Academy of Continuous Professional Education; I. M. Sechenov First Moscow State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияRussian Medical Academy of Continuous Professional EducationRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Московский государственный медико-стоматологический университет им. А. И. Евдокимова» Министерства здравоохранения Российской ФедерацииРоссияA. I. Yevdokimov Moscow State University of Medicine and DentistryRussian Federation20201108202083109122Copyright © Остроумова О.Д., Кочетков А.И., Павлеева Е.Е., Кравченко Е.В., 20202020Остроумова О.Д., Кочетков А.И., Павлеева Е.Е., Кравченко Е.В.Ostroumova O.D., Kochetkov A.I., Pavleeva E.E., Kravchenko E.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/190

Лекарственно-индуцированные нейтропения и агранулоцитоз представляют собой серьезные и потенциально угрожающие жизни осложнения фармакотерапии. Цель работы: систематизация и анализ данных научной литературы о распространенности, факторах риска, патофизиологических механизмах, клинической картине, способах профилактики и лечения лекарственно-индуцированных нейтропении и агранулоцитоза и лекарственных средствах, применение которых наиболее часто вызывает развитие этих состояний. В результате проведенного анализа установлено, что одной из главных причин возникновения лекарственно-индуцированных нейтропении и агранулоцитоза является применение цитотоксических лекарственных средств (алкилирующих агентов, антиметаболитов, таксанов), нестероидных противовоспалительных препаратов, антибиотиков, антитромбоцитарных, антитиреоидных, антиревматических, антиаритмических, антипсихотических лекарственных средств. Частота встречаемости лекарственно-индуцированных нейтропении и агранулоцитоза в целом низкая, от 3 до 16 случаев на 1 млн человек в год. К основным факторам риска развития этих состояний относят пожилой возраст, женский пол, наличие химио- или лучевой терапии в анамнезе, недостаточное питание, коморбидную патологию. При нейтропении и агранулоцитозе вне зависимости от этиологии могут наблюдаться такие симптомы, как лихорадка, озноб, апатия, миалгия, слабость, фарингит, гингивит, синусит, стоматит, бронхит, сепсис. Практических методов для ранней диагностики или предотвращения лекарственно-индуцированных нейтропении и агранулоцитоза не существует. Успешное лечение этих состояний базируется на принципе быстрого распознавания и немедленной отмены лекарственного средства, применение которого потенциально явилось причиной их развития. Профилактика нейтропении, ассоциированной с химиотерапией, заключается в снижении дозы химиотерапевтического агента. Практикующим врачам важно иметь настороженность в отношении риска возникновения лекарственно-индуцированных нейтропении и агранулоцитоза. Необходимо повышать информированность специалистов здравоохранения о методах диагностики, профилактики и особенностях ведения пациентов с данными состояниями.

Drug-induced neutropenia and agranulocytosis are serious and potentially life-threatening complications of pharmacotherapy. The aim of the review was to systematise and analyse scientific literature on the prevalence, risk factors, pathogenesis, clinical picture, methods of prevention and treatment of drug-induced neutropenia and agranulocytosis, and medicinal products that most often lead to their development. The analysis revealed that one of the major reasons of drug-induced neutropenia and agranulocytosis is the use of cytotoxic drugs (alkylating agents, antimetabolites, taxanes), non-steroidal anti-inflammatory drugs, antibiotics, antiplatelet, antithyroid, antirheumatic, antiarrhythmic, and antipsychotic drugs. The incidence of drug-induced neutropenia and agranulocytosis is generally low—from 3 to 16 cases per 1 million patients annually. The main risk factors for the development of these conditions include old age, female sex, history of chemotherapy or radiation therapy, malnutrition, and comorbidities. The symptoms in patients with neutropenia and agranulocytosis regardless of etiology can include fever, chills, apathy, myalgia, weakness, pharyngitis, gingivitis, sinusitis, stomatitis, bronchitis, and sepsis. There are no practical methods for early diagnosis or prevention of drug-induced neutropenia and agranulocytosis. Successful management of these conditions relies on timely identification and immediate withdrawal of the potential causative drug. Prevention of chemotherapy-associated neutropenia may consist in reducing the dose of the chemotherapeutic agent. Practicing physicians should be aware of the risk of drug-induced neutropenia and agranulocytosis. It is important to raise awareness among healthcare professionals of the methods of diagnosis and prevention of these conditions, as well as specific aspects of managing patients with these conditions.

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The authors declare that there are no conflicts of interest present.