Severe methotrexate toxicity in elderly patients under diuretics.

Area of Science:

• Rheumatology
• Clinical Pharmacology
• Geriatrics

Background:

• Low-dose methotrexate (MTX) is widely used for autoimmune diseases.
• Severe MTX toxicity is rare but life-threatening, particularly in elderly patients.
• Understanding risk factors for MTX toxicity is crucial for patient safety.

Purpose of the Study:

• To investigate the clinical presentation, course, and risk factors associated with severe low-dose methotrexate toxicity.
• To identify patient characteristics and concomitant medications that increase the risk of MTX toxicity.

Main Methods:

• Retrospective analysis of patients admitted with severe low-dose MTX toxicity.
• Comparison of these patients with a control group of elderly patients (over 70) without MTX toxicity.
• Multivariate analysis to identify independent risk factors for MTX toxicity.

Main Results:

• Twelve patients experienced severe MTX toxicity, all over 70 years old.
• Patients with toxicity had a lower median estimated glomerular filtration rate (eGFR) prior to the event compared to controls.
• Concomitant use of diuretics, proton pump inhibitors (PPIs), and levetiracetam was more frequent in patients with MTX toxicity.

Conclusions:

• Elderly patients (over 70) with reduced eGFR are at higher risk for severe MTX toxicity.
• The use of diuretics, PPIs, and levetiracetam alongside MTX significantly elevates this risk.
• These findings highlight the need for vigilant monitoring and medication review in elderly MTX users.