I. Cloroquina / hidroxicloroquina y azitromicina. Revisión narrativa de seguridad

Abstract

The SARS-Co-2 pandemic is affecting millions of people, producing hundreds of thousands of deaths, and collapsing healthcare systems worldwide. Due to the lack of specific treatments, repurposed drugs are routinely used in in-hospital patients, though there is no sound-based scientific evidence. The quinine derivatives chloroquine (CQ) and hydroxychloroquine (HCQ) —used as antimalarials, and in autoimmune diseases—, and the antibiotic macrolide azithromycin have been proposed as possible therapies against the SARS-CoV-2 infection and COVID-19. Shortly after this outbreak began, many clinical trials have been registered to evaluate the efficacy of CQ/HCQ, alone or combined with azithromycin, in the treatment of COVID-19 or the prevention of SARS-CoV-2 infection. In the meantime, media information about the possible use of these drugs, politic leaders’ statements and further decisions concerning their efficacy soared public expectations. Both CQ/HCQ and azithromycin are relatively inexpensive and can be administered orally; adverse effects are known at doses used in approved indications. However, their use in a much more significant number of patients increases the risk of occurrence of adverse events. Notably, the potential of both drugs to prolong QTc interval raises concerns about the potentiality to lead to fatal arrhythmias, including torsades de pointes (TdP). The potential blood-glucose-lowering effect of CQ/HCQ could also produce serious adverse effects. The Spanish Pharmacovigilance system has received six cases of serious neuropsychiatric adverse reactions.This narrative review presents a summary of safety information of CQ/HCQ in approved indications, and the emerging experience of their use in the SARS-CoV-2 infection and COVID-19. With randomised clinical trials’ results not available yet, to May 20th 2020, the evidence of efficacy and effectiveness of CQ/HCQ do not suggest a benefit of this use as a treatment of COVID-19. For these purposes, CQ/HCQ alone or in combination with azithromycin should be used only in clinical trials.