Adverse consequences of low-dose methotrexate medication errors: data from French poison control and pharmacovigilance centers

Thierry Vial (1, 2) , Anne Marie Patat (2) , David Boels (3) , Delphine Castellan (4) , Antoine Villa (5) , Hélène Théophile (6) , Romain Torrents (7, 8) , Behrouz Kassai (9)

1 UCBL - Université Claude Bernard Lyon 1
2 HCL - Hospices Civils de Lyon
3 CAPTV Angers - Centre Antipoison et Toxicovigilance du Grand Ouest (Angers)
4 CRPV-Marseille - Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille]
5 CAPTV Paris - Centre antipoison et de toxicovigilance (Paris)
6 CHU Bordeaux
7 CAPTV Marseille - Centre antipoison et de toxicovigilance (Marseille)
8 SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
9 Evaluation et modélisation des effets thérapeutiques

ObjectiveThe objectives of this study are to carefully describe the context of methotrexate medication errors, to details medical consequences and management approaches, and to determine the rate of fatal outcome.MethodsData on methotrexate medication errors were obtained from the French network of poison control and pharmacovigilance centres, which collected and documented reported drug-induced adverse effects. Cases were included if the intake was more than 2-fold the intended weekly dose or a weekly cumulative dose ≥ 30 mg and a follow-up of at least 4 days after the last dose. Data were analysed for demographics, treatment indication, prescribed dose, drug interactions, clinical complications and medical outcomes.ResultsSeventy four patients were included. The causes of methotrexate errors resulted from an erroneous prescription renewal (23.3%), incomprehensiveness of the weekly schedule by patients or at-home caregivers (56.2%) and administration of a wrong dose by a health care professional (20.5%). Of the 70 patients who took methotrexate daily, the mean daily dose received over the whole duration of the error was 9.6 ± 4.1 mg (range 2.5–22.5) with a mean duration of the error of 11.7 ± 12.2 days (range 2 to 90). Thirteen (18%) patients remained asymptomatic and 61 (82%) developed complications of which 46 (62.2%) were severe. Nine (14.8%) patients died within 11 to 45 days after the first dosing error. Compared to patients with no or mild symptoms, those with severe symptoms were more likely to be older (75.6 ± 10.8 vs. 69.5 ± 12.9 years) and to be exposed to a higher cumulative dose (94.8 ± 46.2 vs. 68.0 ± 45.7 mg).ConclusionsThis study confirms that dosing errors with methotrexate can be lethal and persisted despite several warnings from drug agencies. Further measures are awaited from the European Medicine Agency.

Mots clés: Methotrexate; Medication error; Drug toxicity; Mortality

Domaines: Santé publique et épidémiologie

Thierry Vial, Anne Marie Patat, David Boels, Delphine Castellan, Antoine Villa, et al.. Adverse consequences of low-dose methotrexate medication errors: data from French poison control and pharmacovigilance centers. Joint Bone Spine, 2019, 86 (3), pp.351-355. ⟨10.1016/j.jbspin.2018.09.006⟩. ⟨hal-02613008⟩