Clinical outcomes and adverse events in patients hospitalised with COVID‐19, treated with off‐label hydroxychloroquine and azithromycin

Abstract

Aims To assess clinical outcomes and adverse drug events in patients hospitalised with COVID‐19 treated with off‐label hydroxychloroquine (HCQ) and azithromycin (Az). Methods We performed a retrospective analysis of hospitalised patients who had a positive polymerase chain reaction test for SARS‐CoV‐2 and received HCQ plus Az or no targeted therapy. The primary end point was clinical improvement on day 7 defined as either hospital discharge or an improvement of 2 points on a 6‐category ordinal scale. Secondary outcomes included mortality at day 28, intensive care admission, requirement for mechanical ventilation and incidence of adverse events. Results Data from a total of 134 patients were evaluated; 82 patients received HCQ/Az and 52 patients received no targeted therapy. Clinical improvement was seen in 26.8% of patients who received HCQ/Az but this was not significant. The rates of intensive care transfer and mechanical ventilation were higher in the treatment group, but these differences were not significant. Mortality at day 28 was significantly higher in the treatment group (P = .03). Hypoglycaemia elevated liver function tests and QT prolongation were monitored in both groups. The risk of QT prolongation was significantly higher in the treatment group. Treatment was stopped early in 6 (7.3%) patients due to adverse events. Conclusion Although patients who received HCQ/Az were more severely ill the administration of these repurposed drugs did not result in clinical improvement and was associated with a significant increase in toxicity. This descriptive study highlights the importance of monitoring all repurposed agents for adverse events.

Lactoferrin as potential supplementary nutraceutical agent in COVID-19 patients:in vitroandin vivopreliminary evidences

“…In our study, we observed that Lf therapy reduced transaminases levels, decreasing the risk of liver-injury among COVID-19 patients, which is a very frequent complication in SARS-CoV2 severe forms (Wang et al, 2020). Moreover, since several treatments used to treat COVID-19 severe patients, such as hydroxychloroquine, are linked to liver injuries (Kelly et al, 2020), it could be rational to use Lf together with other therapies, in order to increase viral clearance and reduce adverse events of other treatments.…”

Adverse drug reactions in SARS-CoV-2 hospitalised patients: a case-series with a focus on drug–drug interactions

“…As such, caution should always be observed when combining azithromycin with other molecules that increase the QT interval, such as HCQ. In particular, QT prolongation seems to be significantly higher in patients who received the two medications concomitantly [28]. The exact mechanism by which azithromycin and other macrolides prolong the QT interval is through a blockade of the rapid component, IKr, of the delayed rectifier potassium current IK, which is encoded by the hERG [29], similarly to HCQ.…”

“…Considering that QT prolongation could be an asymptomatic and potentially fatal event, it should be always strictly monitored. The risk factors for QT prolongation and TdS are female sex, older age, heart disease, exposure to QT interval prolonging drugs or metabolic inhibitors, bradycardia, and electrolyte disturbance [28]. The cornerstone of the management of acquired QT prolongation includes the identification and discontinuation of any suspected drug and the prompt correction of any metabolic abnormalities [32].…”

Use of hydroxychloroquine and chloroquine in patients with COVID-19: a meta-analysis of randomized clinical trials

“…As for the effects of cardiac conduction, other than those already mentioned, we must consider branch block and atrioventricular block [ 29 ]. CQ and HCQ uses, when associated with azithromycin, increase the risk of hepatotoxicity [ 32 ], cardiotoxicity, and hypoglycemia [ 33 ].…”