The Case
A 16-year-old boy with osteosarcoma developed World Health Organization grade 4 oral mucositis three days after receiving high-dose methotrexate. Extensive ulceration, severe pain, odynophagia, and dysphagia left him unable to maintain adequate oral intake and necessitated partial parenteral nutrition.
Alongside hydration, leucovorin rescue, enhanced oral care, systemic analgesia, and treatment of neutropenia, he received separate doxepin and allopurinol mouthwashes four times daily.
Within 48 hours, his pain decreased to 4/10. Mucosal lesions improved by day 5, and the mucositis resolved to grade 1 by day 7. During subsequent methotrexate cycles, prophylactic allopurinol mouthwash was associated with absent or minimal mucositis despite higher methotrexate doses.
Why This Case Matters
Doxepin may provide topical analgesia, while allopurinol has proposed antioxidant and mucosal-protective effects. Their combined use offers a biologically plausible supportive-care strategy for severe treatment-related mucositis.
However, recovery occurred during several concurrent interventions, methotrexate levels were unavailable, and this single case cannot establish efficacy or determine the contribution of either mouthwash. Controlled studies are needed before routine use can be recommended.
Clinical Take-Home Message
Dual topical doxepin and allopurinol mouthwashes may be considered a hypothesis-generating supportive approach to severe high-dose methotrexate-induced oral mucositis. Careful monitoring and established supportive measures remain essential.
Read the full case report:
Hadizadeh A, Esfahani H, Ghalandari N. Dual topical therapy with doxepin and allopurinol mouthwash for severe methotrexate-induced oral mucositis: a pediatric case report. Journal of Medical Case Reports. 2026.
https://doi.org/10.1186/s13256-026-06588-6