These sources examine the pharmacological profile and clinical management of methotrexate, a medication used to treat malignancies and autoimmune conditions. The drug functions by inhibiting folate metabolism, yet it carries a significant risk of systemic toxicity, particularly affecting the kidneys, lungs, and liver. Research indicates that certain drug-drug interactions, such as with proton pump inhibitors, can dangerously elevate serum levels by slowing drug clearance. Clinical guidelines emphasize the necessity of urinary alkalinisation and vigorous hydration to prevent renal injury during high-dose therapy. Furthermore, the documents detail the use of leucovorin rescue and glucarpidase to mitigate adverse effects and counteract lethal concentrations in the blood. Together, these materials provide a comprehensive framework for balancing the drug's therapeutic benefits against its potential for severe organ damage.