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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">safetyrisk</journal-id><journal-title-group><journal-title xml:lang="ru">Безопасность и риск фармакотерапии</journal-title><trans-title-group xml:lang="en"><trans-title>Safety and Risk of Pharmacotherapy</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2312-7821</issn><issn pub-type="epub">2619-1164</issn><publisher><publisher-name>Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.30895/2312-7821-2024-12-4-396-408</article-id><article-id custom-type="elpub" pub-id-type="custom">safetyrisk-454</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ГЛАВНАЯ ТЕМА: ТЕНЕВЫЕ СТОРОНЫ ФАРМАКОТЕРАПИИ: НЕЖЕЛАТЕЛЬНЫЕ РЕАКЦИИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>MAIN TOPIC: THE DARK SIDE OF PHARMACOTHERAPY: ADVERSE DRUG REACTIONS</subject></subj-group></article-categories><title-group><article-title>Токсические реакции при вероятной и установленной передозировке метотрексата у пациентов ревматологического профиля: серия клинических случаев</article-title><trans-title-group xml:lang="en"><trans-title>Toxic Reactions in Probable and Confirmed Methotrexate Overdose in Rheumatology Patients: A Case Series</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5858-7877</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Докторова</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Doktorova</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Докторова Светлана Алексеевна</p><p>ул. А. Невского, д. 14, г. Калининград, 236041</p></bio><bio xml:lang="en"><p>Svetlana A. Doktorova</p><p>14 Alexander Nevsky St., Kaliningrad 236041</p></bio><email xlink:type="simple">svdoktorova96@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7916-1488</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Андреева</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Andreeva</surname><given-names>I. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Андреева Ирина Вениаминовна, канд. мед. наук, доцент</p><p>ул. Крупской, д. 28, г. Смоленск</p></bio><bio xml:lang="en"><p>Irina I. Andreeva, Cand. Sci. (Med.), Associate Professor</p><p>28 Krupskaya St., Smolensk 214019</p></bio><email xlink:type="simple">Irina.Andreeva@antibiotic.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1207-6144</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кречикова</surname><given-names>Д. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Krechikova</surname><given-names>D. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кречикова Диана Григорьевна, канд. мед. наук</p><p>1-й Краснофлотский переулок, д. 15, г. Смоленск, 214025</p></bio><bio xml:lang="en"><p>Diana G. Krechikova, Cand. Sci. (Med.)</p><p>15 1st Krasnoflotsky Ln., Smolensk 214025</p></bio><email xlink:type="simple">d.krechikova@gmail.com</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1758-3065</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Грабовецкая</surname><given-names>Ю. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Grabovetskaya</surname><given-names>Yu. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Грабовецкая Юлия Юрьевна</p><p>ул. Клиническая, д. 74, г. Калининград, 236016</p></bio><bio xml:lang="en"><p>Yuliya Yu. Grabovetskaya</p><p>74 Klinicheskaya St., Kaliningrad 236016</p></bio><email xlink:type="simple">dr.grabovetskaya@mail.ru</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0001-2185-3649</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мажаева</surname><given-names>О. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Mazhaeva</surname><given-names>O. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мажаева Ольга Сергеевна</p><p>1-й Краснофлотский переулок, д. 15, г. Смоленск, 214025</p></bio><bio xml:lang="en"><p>Olga S. Mazhaeva</p><p>15 1st Krasnoflotsky Ln., Smolensk 214025</p></bio><email xlink:type="simple">mazhdo@yandex.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2503-9580</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рафальский</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Rafalskiy</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Рафальский Владимир Витальевич, д-р мед. наук, профессор</p><p>ул. А. Невского, д. 14, г. Калининград, 236041</p></bio><bio xml:lang="en"><p>Vladimir V. Rafalskiy, Dr. Sci. (Med.), Professor</p><p>14 Alexander Nevsky St., Kaliningrad 236041</p></bio><email xlink:type="simple">v.rafalskiy@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное автономное образовательное учреждение высшего образования «Балтийский федеральный университет имени Иммануила Канта»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Immanuel Kant Baltic Federal University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное образовательное учреждение высшего образования «Смоленский государственный медицинский университет» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Smolensk State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Частное учреждение здравоохранения «Клиническая больница «РЖД-Медицина» города Смоленск»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Clinical Hospital “RZD-Medicine” of Smolensk</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>Государственное бюджетное учреждение здравоохранения «Клинико-диагностическая поликлиника Областной клинической больницы Калининградской области»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Clinical and Diagnostic Outpatient Clinic of the Regional Clinical Hospital of Kaliningrad Region</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>05</day><month>11</month><year>2024</year></pub-date><volume>12</volume><issue>4</issue><fpage>396</fpage><lpage>408</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Докторова С.А., Андреева И.В., Кречикова Д.Г., Грабовецкая Ю.Ю., Мажаева О.С., Рафальский В.В., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Докторова С.А., Андреева И.В., Кречикова Д.Г., Грабовецкая Ю.Ю., Мажаева О.С., Рафальский В.В.</copyright-holder><copyright-holder xml:lang="en">Doktorova S.A., Andreeva I.V., Krechikova D.G., Grabovetskaya Y.Y., Mazhaeva O.S., Rafalskiy V.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.risksafety.ru/jour/article/view/454">https://www.risksafety.ru/jour/article/view/454</self-uri><abstract><sec><title>ВВЕДЕНИЕ</title><p>ВВЕДЕНИЕ. Применение метотрексата в низких дозах (менее 30 мг/нед.) является стандартом терапии ревматологических заболеваний. Передозировка метотрексата вследствие ошибок со стороны пациента или медицинского персонала может привести к развитию тяжелых осложнений и жизнеугрожающих состояний.</p></sec><sec><title>ОПИСАНИЕ СЛУЧАЕВ</title><p>ОПИСАНИЕ СЛУЧАЕВ. Проведен ретроспективный анализ медицинской документации трех клинических случаев вероятной (1 случай) и установленной (2 случая) передозировки метотрексата с развитием токсических реакций у пациентов ревматологического профиля, находившихся в период 2019–2024 гг. в лечебно-профилактических учреждениях Калининградской и Смоленской областей. Анализ включал изучение клинической картины передозировки метотрексата, медицинского анамнеза, сопутствующей терапии, лабораторных показателей и тактики ведения пациентов с момента госпитализации. Все пациенты имели подтвержденные диагнозы ревматологического профиля: псориатический артрит (мужчина, 59 лет) и серопозитивный ревматоидный артрит (женщины, 68 и 57 лет). В качестве базисной противовоспалительной терапии получали метотрексат в дозе от 10 до 20 мг в неделю с обязательным приемом фолиевой кислоты не менее 5 мг в неделю. Пациенты имели сопутствующие заболевания почек, сердечно-сосудистой системы, метаболические нарушения. Основной причиной передозировки метотрексата в описанных клинических случаях явился ежедневный прием пациентом дозы метотрексата, предназначенной для применения один раз в неделю. Симптомы передозировки манифестировали в виде геморрагического синдрома, эрозивно-язвенных поражений слизистых оболочек, диспепсии и изменений лабораторных показателей. В двух случаях установленной передозировки нежелательные реакции проявились через 13 и 14 суток после начала ошибочного применения метотрексата. Летальный исход наступил у двух пациентов на 4-е и 7-е сутки от момента госпитализации; в одном случае наступило выздоровление, пациент был выписан через 40 койко-дней пребывания в стационаре.</p></sec><sec><title>ВЫВОДЫ</title><p>ВЫВОДЫ. Передозировка метотрексата может приводить к нарушениям со стороны кроветворной системы, желудочно-кишечного тракта, кожи и слизистых оболочек с развитием жизнеугрожающих состояний вплоть до летального исхода. Представленные клинические случаи подчеркивают важность четкого информирования пациентов о схеме терапии метотрексатом и возможных симптомах передозировки, что может существенно снизить вероятность такого осложнения и связанных с ним негативных последствий, обеспечивая более безопасное лечение в амбулаторной практике при ревматологических заболеваниях.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>INTRODUCTION</title><p>INTRODUCTION. Low-dose methotrexate (less than 30 mg/week) is the standard therapy for rheumatic diseases. Methotrexate overdose due to errors by patients or medical staff may lead to severe complications and life-threatening conditions.</p></sec><sec><title>CASE DESCRIPTION</title><p>CASE DESCRIPTION. This article presents a retrospective analysis of the medical records of three clinical cases of methotrexate overdose with toxic reactions (one probable and two confirmed cases) observed in rheumatology patients at general and preventive medicine clinics in the Kaliningrad and Smolensk regions in 2019–2024. The analysis examined the clinical presentation of methotrexate overdose, medical history, concomitant therapy, laboratory findings, and patient management strategy from the time of admission. All patients had confirmed rheumatic diagnoses, including psoriatic arthritis (one male, 59 years old) and seropositive rheumatoid arthritis (two females, 68 and 57 years old). As a baseline anti-inflammatory therapy, patients received methotrexate at a dose of 10–20 mg/week with the mandatory addition of folic acid at a dose of at least 5 mg/week. Patients had concomitant renal, cardiovascular, and metabolic disorders. The primary cause of these overdose cases was that the doses prescribed for weekly administration were taken daily. Overdose manifested as haemorrhagic syndrome, erosive and ulcerative mucosal lesions, dyspepsia, and changes in laboratory findings. In two confirmed overdose cases, adverse drug reactions manifested 13 and 14 days after the start of erroneous methotrexate administration. Two patients died on days 4 and 7 from admission, and one patient recovered and was discharged after 40 days of hospital stay.</p></sec><sec><title>CONCLUSIONS</title><p>CONCLUSIONS. Methotrexate overdose can lead to haematopoietic, gastrointestinal, cutaneous, and mucosal disorders and result in life-threatening conditions and even death. The described cases emphasise the importance of clearly informing patients of methotrexate dosing regimens and possible symptoms of overdose. This approach can mitigate the potential risk and adverse consequences of overdose while improving the safety of outpatient methotrexate treatment for rheumatic diseases.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>метотрексат</kwd><kwd>токсичность</kwd><kwd>передозировка</kwd><kwd>панцитопения</kwd><kwd>кровотечения</kwd><kwd>ревматоидный артрит</kwd><kwd>псориатический артрит</kwd><kwd>медицинские ошибки</kwd><kwd>безопасность лекарственных средств</kwd><kwd>клинический случай</kwd></kwd-group><kwd-group xml:lang="en"><kwd>methotrexate</kwd><kwd>toxicity</kwd><kwd>overdose</kwd><kwd>pancytopenia</kwd><kwd>haemorrhages</kwd><kwd>rheumatoid arthritis</kwd><kwd>psoriatic arthritis</kwd><kwd>medication errors</kwd><kwd>drug safety</kwd><kwd>clinical case</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена без спонсорской поддержки</funding-statement><funding-statement xml:lang="en">The study was performed without external funding</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов ЕЛ, Амирджанова ВН, Олюнин ЮА, Муравьев ЮВ, Баранов АА, Зонова ЕВ и др. Применение метотрексата при ревматоидном артрите. Рекомендации Общероссийской общественной организации «Ассоциация ревматологов России». Научно-практическая ревматология. 2023;61(4):435–49. https://doi.org/10.47360/1995-4484-2023-435-449</mixed-citation><mixed-citation xml:lang="en">Nasonov EL, Amirjanova VN, Olyunin YuA, Mura­vyev YuV, Baranov AA, Zonova EV, et al. The use of methotrexate in rheumatoid arthritis. Recommendations of the All-Russian public organization “Association of Rheumatologists of Russia”. Rheumatology Science and Practice. 2023;61(4):435–49 (In Russ.). https://doi.org/10.47360/1995-4484-2023-435-449</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Чичасова НВ, Лила АМ. Метотрексат в лечении ревматоидного артрита и псориатического артрита. Лечащий врач. 2020;(7):42–51. https://doi.org/10.26295/OS.2020.12.42.002</mixed-citation><mixed-citation xml:lang="en">Chichasova NV, Lila AM. Methotrexate in the treatment of rheumatoid arthritis and psoriatic arthritis. Lechaschi Vrach. 2020;(7):42–51 (In Russ.). https://doi.org/10.26295/OS.2020.12.42.002</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Каневская МЗ, Гурская СВ. Метотрексат в лечении ревматических заболеваний. Современная ревматология. 2013;7(4):47–53. https://doi.org/10.14412/1996-7012-2013-2438</mixed-citation><mixed-citation xml:lang="en">Kanevskaya MZ, Gurskaya SV. Methotrexate in the treatment of rheumatic disease. Modern Rheumatology Journal. 2013;7(4):47–53 (In Russ.). https://doi.org/10.14412/1996-7012-2013-2438</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Wang W, Zhou H, Liu L. Side effects of methotrexate therapy for rheumatoid arthritis: a systematic review. Eur J Med Chem. 2018;158:502–16. https://doi.org/10.1016/j.ejmech.2018.09.027</mixed-citation><mixed-citation xml:lang="en">Wang W, Zhou H, Liu L. Side effects of methotrexate therapy for rheumatoid arthritis: a systematic review. Eur J Med Chem. 2018;158:502–16. https://doi.org/10.1016/j.ejmech.2018.09.027</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Weinblatt ME. Toxicity of low dose methotrexate in rheumatoid arthritis. J Rheumatol Suppl. 1985;12 Suppl 12:35–9. PMID: 3913775</mixed-citation><mixed-citation xml:lang="en">Weinblatt ME. Toxicity of low dose methotrexate in rheumatoid arthritis. J Rheumatol Suppl. 1985;12 Suppl 12:35–9. PMID: 3913775</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Kivity S, Zafrir Y, Loebstein R, Pauzner R, Mouallem M, Mayan H. Clinical characteristics and risk factors for low dose methotrexate toxicity: a cohort of 28 patients. Autoimmun Rev. 2014;13(11):1109–13. https://doi.org/10.1016/j.autrev.2014.08.027</mixed-citation><mixed-citation xml:lang="en">Kivity S, Zafrir Y, Loebstein R, Pauzner R, Mouallem M, Mayan H. Clinical characteristics and risk factors for low dose methotrexate toxicity: a cohort of 28 patients. Autoimmun Rev. 2014;13(11):1109–13. https://doi.org/10.1016/j.autrev.2014.08.027</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Perregaard H, Aronson JK, Dalhoff K, Hellebek A. Medication errors detected in non-traditional databases: types of errors in methotrexate dosing as listed in four different Danish registers. Eur J Clin Pharmacol. 2015;71(11):1375–9. https://doi.org/10.1007/s00228-015-1910-3</mixed-citation><mixed-citation xml:lang="en">Perregaard H, Aronson JK, Dalhoff K, Hellebek A. Medication errors detected in non-traditional databases: types of errors in methotrexate dosing as listed in four different Danish registers. Eur J Clin Pharmacol. 2015;71(11):1375–9. https://doi.org/10.1007/s00228-015-1910-3</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Grissinger M. Severe harm and death associated with errors and drug interactions involving low-dose methotrexate. P T. 2018;43(4):191–248. PMID: 29622936.</mixed-citation><mixed-citation xml:lang="en">Grissinger M. Severe harm and death associated with errors and drug interactions involving low-dose methotrexate. P T. 2018;43(4):191–248. PMID: 29622936.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Pannu AK. Methotrexate overdose in clinical practice. Curr Drug Metab. 2019;20(9):714–9. https://doi.org/10.2174/1389200220666190806140844</mixed-citation><mixed-citation xml:lang="en">Pannu AK. Methotrexate overdose in clinical practice. Curr Drug Metab. 2019;20(9):714–9. https://doi.org/10.2174/1389200220666190806140844</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Vial T, Patat AM, Boels D, Castellan D, Villa A, Theo­phile H, et al. Adverse consequences of low-dose methotrexate medication errors: data from French poison control and pharmacovigilance centers. Joint Bone Spine. 2019;86(3):351–5. https://doi.org/10.1016/j.jbspin.2018.09.006</mixed-citation><mixed-citation xml:lang="en">Vial T, Patat AM, Boels D, Castellan D, Villa A, Theo­phile H, et al. Adverse consequences of low-dose methotrexate medication errors: data from French poison control and pharmacovigilance centers. Joint Bone Spine. 2019;86(3):351–5. https://doi.org/10.1016/j.jbspin.2018.09.006</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Ahmadzadeh A, Zamani N, Hassanian-Moghad­dam H, Hadeiy SK, Parhizgar P. Acute versus chro­nic methotrexate poisoning; a cross-sectional study. BMC Pharmacol Toxicol. 2019;20(1):39. https://doi.org/10.1186/s40360-019-0316-8</mixed-citation><mixed-citation xml:lang="en">Ahmadzadeh A, Zamani N, Hassanian-Moghad­dam H, Hadeiy SK, Parhizgar P. Acute versus chro­nic methotrexate poisoning; a cross-sectional study. BMC Pharmacol Toxicol. 2019;20(1):39. https://doi.org/10.1186/s40360-019-0316-8</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Moore TJ, Walsh CS, Cohen MR. Reported medication errors associated with methotrexate. Am J Health Syst Pharm. 2004;61(13):1380–4. https://doi.org/10.1093/ajhp/61.13.1380</mixed-citation><mixed-citation xml:lang="en">Moore TJ, Walsh CS, Cohen MR. Reported medication errors associated with methotrexate. Am J Health Syst Pharm. 2004;61(13):1380–4. https://doi.org/10.1093/ajhp/61.13.1380</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Salgueiro-Vázquez ME, Sáinz Gil M, Fernández Peña S, Martín Arias LH. Medication errors associated with oral administration of methotrexate. Data from spontaneous reporting and medical literature review. Med Clin (Barc). 2017;148(7):330–2. https://doi.org/10.1016/j.medcli.2016.12.003</mixed-citation><mixed-citation xml:lang="en">Salgueiro-Vázquez ME, Sáinz Gil M, Fernández Peña S, Martín Arias LH. Medication errors associated with oral administration of methotrexate. Data from spontaneous reporting and medical literature review. Med Clin (Barc). 2017;148(7):330–2. https://doi.org/10.1016/j.medcli.2016.12.003</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Cansu DÜ, Teke HÜ, Bodakçi E, Korkmaz C. How should we manage low-dose methotrexate-induced pancytopenia in patients with rheumatoid arthritis? Clin Rheumatol. 2018;37(12):3419–25. https://doi.org/10.1007/s10067-018-4242-8</mixed-citation><mixed-citation xml:lang="en">Cansu DÜ, Teke HÜ, Bodakçi E, Korkmaz C. How should we manage low-dose methotrexate-induced pancytopenia in patients with rheumatoid arthritis? Clin Rheumatol. 2018;37(12):3419–25. https://doi.org/10.1007/s10067-018-4242-8</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Singh A, Handa AC. Medication error — a case report of misadventure with methotrexate. JNMA J Nepal Med Assoc. 2018;56(211):711–15. PMID: 30381772.</mixed-citation><mixed-citation xml:lang="en">Singh A, Handa AC. Medication error — a case report of misadventure with methotrexate. JNMA J Nepal Med Assoc. 2018;56(211):711–15. PMID: 30381772.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Nimkar SV, Yelne P, Gaidhane SA, Acharya S, Kumar S. Fatal manifestations of methotrexate overdose in case of psoriasis due to dosing error. Cureus. 20227;14(10):e30041. https://doi.org/10.7759/cureus.30041</mixed-citation><mixed-citation xml:lang="en">Nimkar SV, Yelne P, Gaidhane SA, Acharya S, Kumar S. Fatal manifestations of methotrexate overdose in case of psoriasis due to dosing error. Cureus. 20227;14(10):e30041. https://doi.org/10.7759/cureus.30041</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Isoardi KZ, Harris K, Carmichael KE, Dimeski G, Chan BSH, Page CB. Acute bone marrow suppression and gastrointestinal toxicity following acute oral methotrexate overdose. Clin Toxicol (Phila). 2018;56(12):1204–6. https://doi.org/10.1080/15563650.2018.1484128</mixed-citation><mixed-citation xml:lang="en">Isoardi KZ, Harris K, Carmichael KE, Dimeski G, Chan BSH, Page CB. Acute bone marrow suppression and gastrointestinal toxicity following acute oral methotrexate overdose. Clin Toxicol (Phila). 2018;56(12):1204–6. https://doi.org/10.1080/15563650.2018.1484128</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Knoll K, Anzengruber F, Cozzio A, French LE, Murer C, Navarini AA. Mucocutaneous ulcerations and pancytopenia due to methotrexate overdose. Case Rep Dermatol. 2016;8(3):287–93. https://doi.org/10.1159/000446692</mixed-citation><mixed-citation xml:lang="en">Knoll K, Anzengruber F, Cozzio A, French LE, Murer C, Navarini AA. Mucocutaneous ulcerations and pancytopenia due to methotrexate overdose. Case Rep Dermatol. 2016;8(3):287–93. https://doi.org/10.1159/000446692</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Ajmani S, Preet Singh Y, Prasad S, Chowdhury A, Aggarwal A, Lawrence A, et al. Methotrexate-induced pancytopenia: a case series of 46 patients. Int J Rheum Dis. 2017;20(7):846–51. https://doi.org/10.1111/1756-185x.13004</mixed-citation><mixed-citation xml:lang="en">Ajmani S, Preet Singh Y, Prasad S, Chowdhury A, Aggarwal A, Lawrence A, et al. Methotrexate-induced pancytopenia: a case series of 46 patients. Int J Rheum Dis. 2017;20(7):846–51. https://doi.org/10.1111/1756-185x.13004</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Kent PD, Luthra HS, Michet C Jr. Risk factors for methotrexate-induced abnormal laboratory monitoring results in patients with rheumatoid arthritis. J Rheumatol. 2004;31(9):1727–31. PMID: 15338491</mixed-citation><mixed-citation xml:lang="en">Kent PD, Luthra HS, Michet C Jr. Risk factors for methotrexate-induced abnormal laboratory monitoring results in patients with rheumatoid arthritis. J Rheumatol. 2004;31(9):1727–31. PMID: 15338491</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Teke HU, Ozen M. Low-dose methotrexate induces pancytopenia in rheumatoid arthritis patients: are the risk factors predictors for physicians? Turk J Phys Med Rehabil. 2014;60(1):54–8. https://doi.org/10.5152/tftrd.2014.27870</mixed-citation><mixed-citation xml:lang="en">Teke HU, Ozen M. Low-dose methotrexate induces pancytopenia in rheumatoid arthritis patients: are the risk factors predictors for physicians? Turk J Phys Med Rehabil. 2014;60(1):54–8. https://doi.org/10.5152/tftrd.2014.27870</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Hamed KM, Dighriri IM, Baomar AF, Alharthy BT, Alenazi FE, Alali GH, et al. Overview of methotrexate toxicity: a comprehensive literature review. Cureus. 2022;14(9):e29518. https://doi.org/10.7759/cureus.29518</mixed-citation><mixed-citation xml:lang="en">Hamed KM, Dighriri IM, Baomar AF, Alharthy BT, Alenazi FE, Alali GH, et al. Overview of methotrexate toxicity: a comprehensive literature review. Cureus. 2022;14(9):e29518. https://doi.org/10.7759/cureus.29518</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Leaviss J, Carroll C, Essat M, van der Windt D, Grainge MJ, Card T, et al. Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review. RMD Open. 2024;10(1):e003588. https://doi.org/10.1136/rmdopen-2023-003588</mixed-citation><mixed-citation xml:lang="en">Leaviss J, Carroll C, Essat M, van der Windt D, Grainge MJ, Card T, et al. Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review. RMD Open. 2024;10(1):e003588. https://doi.org/10.1136/rmdopen-2023-003588</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Заборских ИВ, Симоненко ВБ, Сарманаев СХ, Туктарова РР, Юрина ЮО. Клинический случай передозировки метотрексата, особенность диагностики в условиях пандемии COVID-19. Клиническая медицина. 2023;101(4–5):241–6. https://doi.org/10.30629/0023-2149-2023-101-4-5-241-246</mixed-citation><mixed-citation xml:lang="en">Zaborskikh IV, Simonenko VB, Sarmanaev SKh, Tuktarova RR, Yurina YuO. Clinical case of methotrexate overdose, the peculiarity of diagnostics in the conditions of the COVID-19 pandemic. Clinical Medicine (Russian Journal). 2023;101(4–5):241–6 (In Russ.). https://doi.org/10.30629/0023-2149-2023-101-4-5-241-246</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Chan BS, Dawson AH, Buckley NA. What can clinicians learn from therapeutic studies about the treatment of acute oral methotrexate poisoning? Clin Toxicol (Phila). 2017;55(2):88–96. https://doi.org/10.1080/15563650.2016.1271126</mixed-citation><mixed-citation xml:lang="en">Chan BS, Dawson AH, Buckley NA. What can clinicians learn from therapeutic studies about the treatment of acute oral methotrexate poisoning? Clin Toxicol (Phila). 2017;55(2):88–96. https://doi.org/10.1080/15563650.2016.1271126</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Howard SC, McCormick J, Pui C-H, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. Oncologist. 2016;21(12):1471–82. https://doi.org/10.1634/theoncologist.2015-0164</mixed-citation><mixed-citation xml:lang="en">Howard SC, McCormick J, Pui C-H, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. Oncologist. 2016;21(12):1471–82. https://doi.org/10.1634/theoncologist.2015-0164</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Cairns R, Brown JA, Lynch AM, Robinson J, Wylie C, Buckley NA. A decade of Australian methotrexate dosing errors. Med J Aust. 2016;204(10):384. https://doi.org/10.5694/mja15.01242</mixed-citation><mixed-citation xml:lang="en">Cairns R, Brown JA, Lynch AM, Robinson J, Wylie C, Buckley NA. A decade of Australian methotrexate dosing errors. Med J Aust. 2016;204(10):384. https://doi.org/10.5694/mja15.01242</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Гриднева ГИ, Муравьев ЮВ, Глухова СИ, Аронова ЕС, Самаркина ЕЮ, Баймеева НВ. Анализ зависимости между ответом на терапию метотрексатом и его фармакокинетическими показателями при ревматоидном артрите. Современная ревматология. 2022;16(4):15–20. https://doi.org/10.14412/1996-7012-2022-4-15-20</mixed-citation><mixed-citation xml:lang="en">Gridneva GI, Muravyov YuV, Glukhova SI, Aronova ES, Samarkina EYu, Baimeeva NV. Analysis of the relationship between the response to methotrexate therapy and its pharmacokinetic parameters in rheumatoid arthritis. Modern Rheumatology Journal. 2022;16(4):15–20 (In Russ.). https://doi.org/10.14412/1996-7012-2022-4-15-20</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Гриднева ГИ, Муравьев ЮВ, Баймеева НВ, Сыгыр­та ВС, Глухова СИ, Гусева ИА и др. Терапевтический лекарственный мониторинг метотрексата и его метаболитов в эритроцитах и мононуклеарах больных ревматоидным артритом. Современная ревматология. 2020;14(4):60–4.. https://doi.org/10.14412/1996-7012-2020-4-60-64</mixed-citation><mixed-citation xml:lang="en">Gridneva GI, Muravyev YuV, Baimeeva NV, Sygyrta VS, Glukhova SI, Guseva IA, et al. Therapeutic drug monitoring of methotrexate and its metabolites in the red blood cells and mononuclear cells of patients with rheumatoid arthritis. Modern Rheumatology Journal. 2020;14(4):60–4 (In Russ.). https://doi.org/10.14412/1996-7012-2020-4-60-64</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Dervieux T, Greenstein N, Kremer J. Pharmaco­genomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis &amp; Rheumatism. 2006;54(10):3095–103. https://doi.org/10.1002/art.22129</mixed-citation><mixed-citation xml:lang="en">Dervieux T, Greenstein N, Kremer J. Pharmaco­genomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis &amp; Rheumatism. 2006;54(10):3095–103. https://doi.org/10.1002/art.22129</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Brady K, Qu Y, Stimson D, Apilado R, Vezza Alexander R, Reddy S, et al. Transition of methotrexate poly­glutamate drug monitoring assay from venipuncture to capillary blood-based collection method in rheumatic diseases. J Appl Lab Med. 2019;4(1):40–9. https://doi.org/10.1373/jalm.2018.027730</mixed-citation><mixed-citation xml:lang="en">Brady K, Qu Y, Stimson D, Apilado R, Vezza Alexander R, Reddy S, et al. Transition of methotrexate poly­glutamate drug monitoring assay from venipuncture to capillary blood-based collection method in rheumatic diseases. J Appl Lab Med. 2019;4(1):40–9. https://doi.org/10.1373/jalm.2018.027730</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Korell J, Stamp LK, Barclay ML, Dalrymple JM, Drake J, Zhang M, et al. A population pharmacokinetic model for low-dose methotrexate and its polyglutamated metabolites in red blood cells. Clin Pharmacokinet. 2013;52(6):475–85. https://doi.org/10.1007/s40262-013-0052-y</mixed-citation><mixed-citation xml:lang="en">Korell J, Stamp LK, Barclay ML, Dalrymple JM, Drake J, Zhang M, et al. A population pharmacokinetic model for low-dose methotrexate and its polyglutamated metabolites in red blood cells. Clin Pharmacokinet. 2013;52(6):475–85. https://doi.org/10.1007/s40262-013-0052-y</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">van de Meeberg MM, Hebing RCF, Nurmohamed MT, Fidder HH, Heymans MW, Bouma G, et al. A meta-analysis of methotrexate polyglutamates in relation to efficacy and toxicity of methotrexate in inflammatory arthritis, colitis and dermatitis. Br J Clin Pharmacol. 2023;89(1):61–79. https://doi.org/10.1111/bcp.15579</mixed-citation><mixed-citation xml:lang="en">van de Meeberg MM, Hebing RCF, Nurmohamed MT, Fidder HH, Heymans MW, Bouma G, et al. A meta-analysis of methotrexate polyglutamates in relation to efficacy and toxicity of methotrexate in inflammatory arthritis, colitis and dermatitis. Br J Clin Pharmacol. 2023;89(1):61–79. https://doi.org/10.1111/bcp.15579</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Gilani S, Khan DA, Khan FA, Ahmed M. Adverse effects of low dose methotrexate in rheumatoid arthritis patients. J Coll Physicians Surg Pak. 2012;22(2):101–4. PMID: 22313647</mixed-citation><mixed-citation xml:lang="en">Gilani S, Khan DA, Khan FA, Ahmed M. Adverse effects of low dose methotrexate in rheumatoid arthritis patients. J Coll Physicians Surg Pak. 2012;22(2):101–4. PMID: 22313647</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Shoda H, Inokuma S, Yajima N, Tanaka Y, Oobaya­shi T, Setoguchi K. Higher maximal serum concentration of methotrexate predicts the incidence of adverse reactions in Japanese rheumatoid arthritis patients. Mod Rheumatol. 2007;17(4):311–6. https://doi.org/10.1007/s10165-007-0582-y</mixed-citation><mixed-citation xml:lang="en">Shoda H, Inokuma S, Yajima N, Tanaka Y, Oobaya­shi T, Setoguchi K. Higher maximal serum concentration of methotrexate predicts the incidence of adverse reactions in Japanese rheumatoid arthritis patients. Mod Rheumatol. 2007;17(4):311–6. https://doi.org/10.1007/s10165-007-0582-y</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Takahashi C, Kaneko Y, Okano Y, Taguchi H, Oshima H, Izumi K, et al. Association of erythrocyte methotrexate-polyglutamate levels with the efficacy and hepatotoxicity of methotrexate in patients with rheumatoid arthritis: a 76-week prospective study. RMD Open. 2017;3(1):e000363. https://doi.org/10.1136/rmdopen-2016-000363</mixed-citation><mixed-citation xml:lang="en">Takahashi C, Kaneko Y, Okano Y, Taguchi H, Oshima H, Izumi K, et al. Association of erythrocyte methotrexate-polyglutamate levels with the efficacy and hepatotoxicity of methotrexate in patients with rheumatoid arthritis: a 76-week prospective study. RMD Open. 2017;3(1):e000363. https://doi.org/10.1136/rmdopen-2016-000363</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Silva MF, Ribeiro C, Gonçalves VMF, Tiritan ME, Lima Á. Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: a brief review. Biomed Chromatogr. 2018;32(5):e4159. https://doi.org/10.1002/bmc.4159</mixed-citation><mixed-citation xml:lang="en">Silva MF, Ribeiro C, Gonçalves VMF, Tiritan ME, Lima Á. Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: a brief review. Biomed Chromatogr. 2018;32(5):e4159. https://doi.org/10.1002/bmc.4159</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Maksimovic V, Pavlovic-Popovic Z, Vukmirovic S, Cvejic J, Mooranian A, Al-Salami H, et al. Molecular mechanism of action and pharmacokinetic properties of methotrexate. Mol Biol Rep. 2020;47(6):4699–708. https://doi.org/10.1007/s11033-020-05481-9</mixed-citation><mixed-citation xml:lang="en">Maksimovic V, Pavlovic-Popovic Z, Vukmirovic S, Cvejic J, Mooranian A, Al-Salami H, et al. Molecular mechanism of action and pharmacokinetic properties of methotrexate. Mol Biol Rep. 2020;47(6):4699–708. https://doi.org/10.1007/s11033-020-05481-9</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Hidi I, Mühlig A, Jahn M, Liebold F, Cialla D, Weber K, et al. LOC-SERS: towards point-of-care diagnostic of methotrexate. Anal Methods. 2014;6(12):3943–7. https://doi.org/10.1039/C3AY42240B</mixed-citation><mixed-citation xml:lang="en">Hidi I, Mühlig A, Jahn M, Liebold F, Cialla D, Weber K, et al. LOC-SERS: towards point-of-care diagnostic of methotrexate. Anal Methods. 2014;6(12):3943–7. https://doi.org/10.1039/C3AY42240B</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Shea B, Swinden MV, Tanjong Ghogomu E, Ortiz Z, Katchamart W, Rader T, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013;(5):CD000951. https://doi.org/10.1002/14651858.cd000951.pub2</mixed-citation><mixed-citation xml:lang="en">Shea B, Swinden MV, Tanjong Ghogomu E, Ortiz Z, Katchamart W, Rader T, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013;(5):CD000951. https://doi.org/10.1002/14651858.cd000951.pub2</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Комиссарова ВА. Меры минимизации рисков в фармаконадзоре: обзор отечественного и зарубежного опыта. Качественная клиническая практика. 2019;(3):33–43. EDN: LLQEPG</mixed-citation><mixed-citation xml:lang="en">Komissarova VA. Risk minimization measures in pharmacovigilance: review of national and international experience. Good Clinical Practice. 2019;(3):33–43 (In Russ.). EDN: LLQEPG</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Лукина ЮВ, Кутишенко НП, Марцевич СЮ, Шепель РН, Драпкина ОМ. Методические рекомендации: «Приверженность к лекарственной терапии у больных хроническими неинфекционными заболеваниями. Решение проблемы в ряде клинических ситуаций». Профилактическая медицина. 2020;23(3–2):42–60. https://doi.org/10.17116/profmed20202303242</mixed-citation><mixed-citation xml:lang="en">Lukina YuV, Kutishenko NP, Martsevich SYu, Shepel RN, Drapkina OM. Methodological recommendations ‘Adherence to drug therapy in patients with chronic non-communicable diseases. Addressing the problem in a number of clinical situations’. Russian Journal of Preventive Medicine. 2020;23(3–2):42–60 (In Russ.) https://doi.org/10.17116/profmed20202303242</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
