Poisoning related to therapeutic error in prolonged low-dose methotrexate treatment.

Aims: To study the predictive factors for the development of clinical manifestations in poisoning due to the erroneous taking of low-dose methotrexate (MTX).

Methods: A retrospective observational study was performed. Only cases of erroneous administration in non-oncologic outpatients were included (July 2008-March 2020).

Results: Forty-one cases were included. All patients were taking MTX for the first time. In 36 cases, patients took MTX daily instead of weekly. In the other five patients, MTX was sold instead of methylergometrine. Clinical manifestations were absent in 12/41 patients (29.3%). All 29 (70.7%) symptomatic patients recognized the medication error when they developed clinical manifestations: dermatological, haematological and gastrointestinal symptoms. Statistical results showed that symptomatic patients were older, received a higher amount of total dose and were treated for longer. Moreover, the probability of being symptomatic increases as a function of age and of total dose. Asymptomatic patients were treated with folinic acid (30 mg/m /day) for 5 days. Symptomatic patients were treated with folinic acid together with treatments for the specific clinical manifestations. No patients were treated with glucarpidase. All patients fully recovered.

Conclusions: When MTX is prescribed for the first time, it is important to clearly communicate with patients to avoid therapeutic errors. In our experience, age, total dose taken and number of days of assumption are predictive for the presence/absence of clinical manifestations. These parameters must be evaluated together to identify patients needing maximum starting treatment with folinic acid and closer monitoring.