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Joint Bone Spine
Volume 86, n° 3
pages 351-355 (mai 2019)
Doi : 10.1016/j.jbspin.2018.09.006
accepted : 6 September 2018
Original Articles

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

Thierry Vial a, , Anne Marie Patat a, David Boels b, Delphine Castellan c, Antoine Villa d, Hélène Theophile e, Romain Torrents f, Behrouz Kassai a
a Department of pharmacotoxicology, poison control and regional pharmacovigilance centres, hospices civils de Lyon, 69424 Lyon, France 
b Poison control centre, university hospitals, 49033 Angers, France 
c Regional pharmacovigilance centre, university hospitals, 13009 Marseille, France 
d Poison control centre, GH–Fernand Widal, Lariboisière, Saint-Louis, university hospitals, 75475 Paris, France 
e Regional pharmacovigilance centre, university hospitals, 33076 Bordeaux, France 
f Poison control centre, university hospitals and Aix-Marseille university, Inserm, SESSTIM UMR 912, 13274 Marseille, France 

Corresponding author at: Service hospitalo-universitaire de pharmacotoxicologie, hospices civils de Lyon, 162, avenue Lacassagne, 69424 Lyon cedex 03, France.Service hospitalo-universitaire de pharmacotoxicologie, hospices civils de Lyon162, avenue LacassagneLyon cedex 0369424France

Despite warnings from national drug agencies or public institutions, oral methotrexate medication errors still occur.
The adverse consequences of these errors are potentially very severe and death can be observed after as little as four consecutive days of error.
A substantial number of medication errors resulted from prescription renewal and administration of a wrong dose during hospitalization or in a nursing home.

The full text of this article is available in PDF format.

The 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.


Data 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.


Seventy 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).


This 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.

The full text of this article is available in PDF format.

Keywords : Methotrexate, Medication error, Drug toxicity, Mortality

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