Methotrexate overdose in clinical practice

Background: 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. 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 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. Results: 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. Conclusion: 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.