Safety profile of methotrexate used off-label in ectopic pregnancy: an active monitoring study based on a Chinese hospital pharmacovigilance system.

OBJECTIVE:Methotrexate (MTX) is characterized as first-line therapy although its indication of ectopic pregnancy is off-label use. We aimed to conduct a retrospective cohort study to investigate the incidence, characteristics of adverse drug reactions (ADRs) of MTX, provide valuable insights for medical workers. METHODS:Basing on China Hospital Pharmacovigilance System (CHPS), a retrospective analysis was performed to evaluate the safety of MTX (n = 672). An active monitoring model was set to detect ADR signals from the hospital information system. Frequency, Common Terminology Criteria for Adverse Events (CTCAE) grade proportion and association of dose exposure with ADRs were presented as outcomes. RESULTS:The total incidence of ADRs was 54.0%. Anaemia (37.6%) was the most frequent ADR, followed by hepatic function abnormal (11.3%), hyperuricemia (6.1%), neutropenia (4.6%), leukopenia (4.0%), and dyslipidaemia (2.5%). For the composition of all ADRs, CTCAE grade one, two and three dominated for 86.3%, 12.1% and 1.6%, respectively. The severity of hepatic function abnormal was more serious in the two-dose exposed group (p = .021), while other types of ADRs had no statistical or clinical differences. Logistic regression analysis showed the incidence of any ADRs (OR 1.87 [1.31-2.64]; p = .001), hepatic function abnormal (OR 2.75 [1.69-4.48]; p < .001), dyslipidaemia (OR 5.15 [1.87-14.13]; p = .001) were significantly higher in the two-dose exposed group. After adjusted, the positive associations were still maintained. CONCLUSIONS:MTX is quite safe in ectopic pregnancy, despite its mild to moderate hematotoxicity, hepatotoxicity and nephrotoxicity. Taking CHPS can present the accurate denominator of the incidence of adverse drug reactions into account, our study advocates that it may have great potential to be used as an active monitoring tool for off-label drug use risk management.