Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Curr Drug Metab. 2019;20(9):714-719. doi: 10.2174/1389200220666190806140844.
A folic-acid antagonist, methotrexate, is one of the most commonly prescribed drugs with its expanding use in clinical practice. The drug requires regular monitoring given its wide range of adverse effects including bone marrow suppression, hepatic or renal dysfunction, gastrointestinal distress, mucocutaneous damage, and neurotoxicity. The toxicity usually occurs rapidly and leads to severe neutropenia, sepsis, and advanced renal failure that are difficult to manage.
This review is an update for the clinicians to understand the pharmacology, clinical features, laboratory evaluation, and treatment of patients with methotrexate overdose. High-quality literature of the past six decades was collected and reviewed in this article. Several landmark articles were reviewed using PubMed, EMBASE Ovid, and the Cochrane Library, that have important implications in current clinical practice.
Methotrexate overdose has complex toxicokinetic and produces myriad clinical features mimicking conditions of lesser severity. Organ dysfunction related to bone marrow, kidney or central nervous system is lifethreatening. The management should focus on high-quality supportive care, antidotal therapy (folinic acid and carboxypeptidase- G2) and plasma alkalization.
In accordance with the dictum "prevention is better than cure", the author emphasizes on the role of patient education, regular clinical observation, and laboratory monitoring for prompt recognition and diagnosis of methotrexate overdosing at the earliest stage.
叶酸拮抗剂甲氨蝶呤是临床实践中最常开的药物之一，其应用范围不断扩大。由于其广泛的不良反应，包括骨髓抑制、肝肾功能障碍、胃肠道不适、黏膜皮肤损伤和神经毒性，需要定期监测。该药物的毒性通常发生迅速，导致严重的中性粒细胞减少症、败血症和难以治疗的晚期肾衰竭。
本文旨在为临床医生提供甲氨蝶呤过量的药理学、临床特征、实验室评估和治疗方面的最新知识。本文综述了过去六十年的高质量文献，使用 PubMed、EMBASE Ovid 和 Cochrane 图书馆等检索工具对一些具有重要临床意义的标志性文章进行了回顾。
甲氨蝶呤过量的毒性动力学复杂，产生多种类似于较轻严重程度的临床特征。与骨髓、肾脏或中枢神经系统相关的器官功能障碍是危及生命的。治疗重点应放在高质量的支持性护理、解毒治疗（亚叶酸和羧肽酶-G2）和血浆碱化上。
根据“预防胜于治疗”的原则，作者强调了患者教育、定期临床观察和实验室监测的作用，以便在最早阶段及时识别和诊断甲氨蝶呤过量。
