Methotrexate-Associated Gastrointestinal Toxicity

Prevention and Management Strategies

• The British Journal of Dermatology recommends folic acid supplementation (1-5 mg daily on non-methotrexate days) to reduce gastrointestinal adverse effects, and taking medication before bedtime or with food may reduce nausea 1
• The Journal of the American Academy of Dermatology suggests that dividing the weekly dose into 3 doses given every 12 hours may help tolerate gastrointestinal adverse effects, and subcutaneous administration may reduce GI side effects compared to oral dosing 2
• The American Academy of Dermatology and British Journal of Dermatology recommend considering subcutaneous administration to reduce GI side effects, and folic acid supplementation to reduce gastrointestinal adverse effects 1, 2
• Praxis Medical Insights recommends stopping methotrexate during acute illness, infection, or hospitalization when GI symptoms develop, and withholding it if severe mucositis or enteritis develops 3
• The British Journal of Dermatology and Praxis Medical Insights recommend dose reduction (50% reduction for creatinine clearance 20-50 mL/min) or complete avoidance (creatinine clearance <20 mL/min) in patients with renal impairment to prevent toxicity 1, 4

Treatment of Toxicity

• Praxis Medical Insights recommends leucovorin (folinic acid) rescue for significant toxicity, and monitoring complete blood count, as GI toxicity may accompany bone marrow suppression 4