Off-label use of hydroxychloroquine in COVID-19: analysis of reports of suspected adverse reactions from the Italian National Network of Pharmacovigilance

This study aimed to characterize adverse drug reactions (ADRs) to hydroxychloroquine in the setting of Covid-19, occurring in Italy in the period March-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 analysed for their incidence, seriousness, outcome, co-administered drugs, MedDRA classification. 306 reports were gathered for the quarter of 2020: 54 % non-serious and 46 % serious, and half of the latter required either the hospitalisation 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 % non-serious and 47 % serious, but no death 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 ADR, QT prolongation and diarrhea significantly increased with hydroxychloroquine dosage. Co-administration 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. This article is protected by copyright. All rights reserved.