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.