Antimalarials and macrolides: a review of off-label pharmacotherapies during the first wave of the SARS-CoV-2 pandemic

Abstract

We critically analyzed clinical trials performed with chloroquine (CQ) and hydroxychloroquine (HCQ) with or without macrolides during the first wave of COVID-19 and discussed the design and limitations of peer-reviewed studies from January to July 2020. Seventeen studies were eligible for the discussion. CQ and HCQ did not demonstrate clinical advantages that justified their inclusion in therapeutic regimens of free prescription for treatment or prophylactic purposes, as suggested by health authorities, including in Brazil, during the first wave. Around August 2020, robust data had already indicated that pharmacological effects of CQ, HCQ and macrolides as anti-SARS-CoV-2 molecules were limited to in vitro conditions and largely based on retrospective trials with low quality and weak internal validity, which made evidence superficial for decision-making. Up to that point, most randomized and nonrandomized clinical trials did not reveal beneficial effects of CQ or HCQ with or without macrolides to reduce lethality, rate of intubation, days of hospitalization, respiratory support/mechanical ventilation requirements, duration, type and number of symptoms, and death and were unsuccessful in increasing virus elimination and/or days alive in hospitalized or ambulatory patients with COVID-19. In addition, many studies have demonstrated that side effects are more common in CQ-or HCQ-treated patients.

Uso de cloroquina, azitromicina e ivermectina durante a pandemia da COVID-19: Uma revisão integrativa

“…As concentrações sob o regime de dosagem atualmente recomendado estão abaixo da margem de segurança para efeitos colaterais, o que sugere que esses regimes de dosagem são geralmente seguros (Meo et al, 2020) Relatar as características biológicas, moleculares, farmacológicas e clínicas da cloroquina e hidroxicloroquina para o tratamento da COVID-19 Não foram encontradas evidências claras de benefícios da terapia com cloroquina para a infecção ambulatorial inicial ou para a profilaxia (Das et al, 2020) Avaliar Autores (Axfors et al, 2021;Das et al, 2020;Ferreira et al, 2023;Gumilang et al, 2021;Kashour et al, 2021;Meo et al, 2020;Nicol et al, 2020;Tleyjeh et al, 2021;Yao et al, 2021) Farmacocinética -Dose única: 155 mg de hidroxicloroquina e 300 mg ou 600 mg de cloroquina; Não se investigou: parâmetros de exposição, tempo para atingir a concentração sérica máxima e interação com alimentos na absorção; -Distribuição: concentrada nas hemácias, com ligação média a proteínas plasmáticas de 59% (30 a 50% para a hidroxicloroquina), além de baço, pulmões, rins e fígado; -Metabolização: hepática; -Eliminação: renal de 30 a 60 dias.…”