Methotrexate-induced pancytopenia: clinical characteristics, medication errors, and outcomes in a tertiary care centre: a retrospective single-centre study

Methotrexate (MTX) is a widely prescribed disease-modifying antirheumatic drug (DMARD) used at ≤ 25 mg/week in inflammatory conditions. Although effective, MTX-induced Pancytopenia remains a serious adverse event, often resulting from medication errors, idiosyncratic reactions, comorbidities, or polypharmacy. To comprehensively characterize methotrexate-induced Pancytopenia’s clinical profile, risk factors, and outcomes. A retrospective analysis was conducted on patients diagnosed with MTX-induced Pancytopenia between 2015 and 2024. Pancytopenia was defined as WBC < 3,500/mm³, Hb < 11 g/dL, and platelets < 150,000/mm³; severe pancytopenia met more stringent thresholds (WBC < 2,000/mm³, Hb < 10 g/dL, platelets < 50,000/mm³). Among 50 patients (35 females, median age 59.5 years), 48 had rheumatoid arthritis and 2 had psoriasis. The median MTX dose was 10 mg/week. Common symptoms included generalized weakness (n = 47), fatigue (n = 42), fever (n = 37), oral ulcers (n = 31), bleeding (n = 11), and skin lesions (n = 10). Severe Pancytopenia occurred in 46% (n = 23) and was associated with significantly higher mortality (26.1% vs. 7.4%; p = 0.04). Medication errors were identified in 26 (52%) cases, mostly at the patient level (n = 23). Time-to-onset analysis revealed a bimodal distribution: early onset (1–4 weeks, median 2 weeks) in error cases, and delayed onset (6–12 months, median 8 months) in error-free patients. Severe Pancytopenia was more frequent in early-onset cases (61% vs. 29%; p = 0.02). Eight patients died despite intervention. MTX-induced Pancytopenia is frequently attributable to preventable errors. Early-phase vigilance, patient education, clear dosing instructions, and systemic safeguards are essential to reduce life-threatening toxicity.