Dual topical therapy with doxepin and allopurinol mouthwash for severe methotrexate-induced oral mucositis: a pediatric case report

High-dose methotrexate (HD-MTX) is a cornerstone of chemotherapy for pediatric osteosarcoma but frequently induces severe oral mucositis, a dose-limiting toxicity characterized by painful ulceration and impaired oral function. While standard supportive care includes leucovorin rescue, hydration, and analgesics, topical agents like doxepin mouthwash offer pain relief, and allopurinol may provide mucosal protection through antioxidant effects. We report a 16-year-old male with osteosarcoma who developed World Health Organization grade 4 oral mucositis on day 3 following his first cycle of HD-MTX (10 g/m 2 ). The symptoms included severe odynophagia, dysphagia, and extensive ulcerative lesions, necessitating partial parenteral nutrition. Treatment involved dual topical therapy with doxepin (0.5% solution) and allopurinol (1 mg/mL) mouthwashes, administered 15 mL four times daily, alongside enhanced oral hygiene and systemic analgesics. Pain scores reduced from severe to 4/10 within 48 h, with mucosal improvement by day 5 and resolution to grade 1 by day 7. No significant adverse effects were noted. In subsequent cycles, prophylactic allopurinol mouthwash minimized or prevented mucositis recurrence despite higher MTX doses. This single case is suggestive of a possible role for combined doxepin and allopurinol mouthwashes for managing severe high-dose MTX-induced oral mucositis in adolescents. Mechanistically supported by doxepin’s analgesic properties and allopurinol’s antioxidant and metabolic modulation, this dual approach merits further evaluation in randomized controlled trials to optimize supportive care in pediatric oncology.