This study aimed to characterize
adverse drug reactions (ADRs) to
hydroxychloroquine in the setting of
COVID-19, occurring in Italy in the period March to May 2020. The analysis of the combination
therapy with
azithromycin or/and
lopinavir/
ritonavir as well as a comparison with ADRs reported throughout 2019 was performed. ADRs collected by the Italian National Network of Pharmacovigilance were analyzed for their incidence, seriousness, outcome, coadministered drugs, and Medical Dictionary for Regulatory Activities classification. A total of 306 reports were gathered for the quarter of 2020: 54% nonserious and 46% serious, and half of the latter required either the hospitalization or its prolongation. However, most of them were either completely recovered (26%) or in the process of recovery (45%), except for 9 fatal cases. Throughout 2019, 38 reports were collected, 53% nonserious and 47% serious, but no deaths had been reported.
Diarrhea, prolonged QT interval, and hypertransaminasemia were the most frequently ADRs reported in 2020, significantly higher than 2019 and specific for
COVID-19 subjects treated with
hydroxychloroquine. The logistic regression analyses demonstrated that the likelihood of serious ADRs, QT prolongation, and
diarrhea significantly increased with
hydroxychloroquine dosage. Coadministration of
lopinavir/
ritonavir and
hydroxychloroquine showed a positive correlation with
diarrhea and hypertransaminasemia and a negative relationship with the ADR seriousness. The combination
therapy with
azithromycin was another independent predictor of a serious ADR.
Off-label use of
hydroxychloroquine for
COVID-19, alone or in combination regimens, was associated with increased incidence and/or seriousness of specific ADRs in patients with additional risk factors caused by the
infection.