Disproportionality analysis
Table 2 shows the disproportionality analysis results for the ADRs for which a statistically significant association was found in one of the two periods. As shown, for certain ADRs there were differences between these two periods. There were some statistically significant associations with several ADRs in the pandemic period, but not in the previous period. Such was the case of cardiac arrhythmias, to be more specific, the Torsade de Pointes /QT prolongation (TdP/QTp) with a ROR (-ROR) equal to 132.8 (76.7) and 39 cases reported during this period; severe hepatic disorders, 18.7 (14.7); dyslipidaemias, 12.1 (6.1); shock, 9.5 (6.9); and ischaemic colitis, 8.9 (2.6). In the pre-pandemic period, there was a statistically significant association with a number of malignancies, haematopoietic cytopaenias, agranulocytosis, and interstitial pulmonary disease, with the following ROR (-ROR) values: 2.3 (1.3), 2.5 (1.7), 3.2 (1.9), 5.0 (2.6), respectively. Some ADRs presented statistically significant disproportion in both periods, though their incidence was higher during the pandemic period. Some example of this are rhabdomyolysis/myopathy, which ROR increased from 5.2 to 8.0; haemolytic disorders (from 3.6 to 6.6), and suicidal/self-injury behaviour (from 3.1 to 5.9). On the contrary, in the case of retinal disturbances, statistical disproportion dropped from 15.4 in the pre-pandemic period to 5.1 in the pandemic period.
Concerning the analysis on the potential interactions (see Table 3), the Ω statistic, as estimated for the most frequently reported active ingredients and the most relevant ADRs, indicated that some ADRs could be increasing with the use of HCQ concomitantly with other drugs as follow: azithromycin, ceftriaxone or lopinavir for TdP/QTp; azithromycin, ceftriaxone and tocilizumab for hepatic disorders, and azithromycin and ceftriaxone for dyslipidaemias. These interactions were not found in the period before the Covid-19 pandemic outburst.