Methotrexate overdose in clinical practice

摘要

Background: A folic-acid antagonist, methotrexate, is one of the most commonly prescribed drugs withits expanding use in clinical practice. The drug requires regular monitoring given its wide range of adverse effectsincluding 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 renalfailure that are difficult to manage.Objective and Methods: 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 sixdecades was collected and reviewed in this article. Several landmark articles were reviewed using PubMed, EMBASEOvid, and the Cochrane Library, that have important implications in current clinical practice.Results and Conclusion: Methotrexate overdose has complex toxicokinetic and produces myriad clinical featuresmimicking conditions of lesser severity. Organ dysfunction related to bone marrow, kidney or central nervous systemis life-threatening. The management should focus on high-quality supportive care, antidotal therapy (folinic acid andcarboxypeptidase-G2) and plasma alkalization. In accordance with the dictum “prevention is better than cure”, theauthor emphasizes on the role of patient education, regular clinical observation, and laboratory monitoring forprompt recognition and diagnosis of methotrexate overdosing at the earliest stage.