{
  "abstract": "Background and Importance Methotrexate (MTX)–related neurotoxicity in children ranges from transient focal deficits and seizures to toxic leukoencephalopathy. Dextromethorphan (DXM), an N-methyl-D-aspartate (NMDA)-receptor antagonist, is used during acute episodes and as secondary prophylaxis to prevent recurrence after MTX re-exposure, but real-world paediatric evidence remains limited.Aim and Objectives To describe the real-world use, effectiveness, and safety of DXM for treatment and/or prophylaxis of MTX-related neurotoxicity in a tertiary paediatric hospital.Material and Methods Retrospective observational study of paediatric patients who received DXM with MTX between January/2020 and September/2025. Variables included demographics (age, sex, weight); DXM therapy (dose, duration, indication, adverse events (AEs)); MTX therapy (intrathecal(IT)/intravenous (IV)); timing from MTX to symptoms and from symptoms to first DXM dose; brain MRI; acute clinical resolution and neurological sequelae of previous or acute MTX-neurotoxicity at 3 and 12 months. Descriptive statistics are reported as median (range).Results Thirty-two patients were included (female 59.4%). Age at DXM start was 9.23 (1.34–18.68) years; weight 35.3 (10.3–71.8) kg. Indication: treatment 20/32 (62.5%) and prophylaxis 12/32 (37.5%). Overall DXM dose was 40 (8–75) mg, 1.03 (0.33–1.67) mg/kg, for 6 (1–25) days. In treatment patients (n=20), dose was 41 (8–75) mg, 1.01 (0.33–1.63) mg/kg for 6.5 (1–25) days; in prophylaxis patients (n=12), 30 (25–60) mg, 1.04 (0.70–1.67) mg/kg for 4 (2–10) days. DXM-related AEs occurred in 1/32 (3.1%), non-serious. MTX route: IV 23/32 (71.9%), IT 9/32 (28.1%). Time from MTX to neurotoxicity was 5.5 (0–25) days (n=20). Time from symptom onset to first treatment DXM dose was 0 (0–3) days. Brain MRI was compatible with previous or acute MTX neurotoxicity in 13/21 (61.9%) among those with MRI performed. Clinical resolution of acute MTX-neurotoxicity was documented in 20/20 (100%) treatment patients. Persistent neurological sequelae of previous or acute MTX-neurotoxicity at 3 months were recorded in 6/32 (18.8%); at 12 months, 0/29 among those with available follow-up had persistent sequelae.Conclusion and Relevance In this real-world paediatric cohort, DXM appeared feasible and clinically useful for managing and preventing MTX-related neurotoxicity. Nonetheless, further prospective, controlled studies are necessary to corroborate and extend these results and to standardise response criteria.Conflict of Interest No conflict of interest",
  "authors": [
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "A Merino Pardo"
    },
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "E Algarra Sánchez"
    },
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "B Arce Abaitua"
    },
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "MI González Rodríguez"
    },
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "A Abril Cabero"
    },
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "B Leal Pino"
    },
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "E Nieto Mártil"
    },
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "L Fernández Romero"
    },
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "B Riva De La Hoz"
    },
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "M Echávarri De Miguel"
    },
    {
      "affiliations": [
        "Hospital Infantil Universitario Niño Jesús, Pharmacy Department, Madrid, Spain"
      ],
      "name": "MT Pozas Del Río"
    }
  ],
  "title": "4CPS-222 Use of dextromethorphan for treatment and prophylaxis of methotrexate-related neurotoxicity in a real-world paediatric cohort",
  "uid": "778498dc-d23b-5736-9619-39017c5c630e"
}