Off label, compassionate and irrational use of medicines in Covid-19 pandemic, health consequences and ethical issues

Abstract

When Covid-19 emerged in December last year, there was no vaccine nor was there specific effective treatment for this fast-spreading and life-threatening viral respiratory infection. Clinical trials were planned and are in progress to investigate whether drugs used for influenza, HIV and other viruses, and also anthelmintics (ivermectin, nitazoxanide, niclosamide), and antimalarials (chloroquine, hydroxychloroquine) showing antiviral activity in in vitro assays, are effective and safe for Covid-19. So far there is no convincing evidence that these antiviral and antiparasitic drugs are of any benefit for Covid-19. Notwithsanding the absence of evidence of clinical efficacy, these drugs are widely used outside of clinical trials (off label) for prophylaxis and treatment of this viral infection. The rationale behind the prescription of macrolide antibiotics (azithromycin) for Covid-19 is obscure as well. The widespread prescription and use of drugs of unproven efficacy and safety for Covid-19 is at odds with the rational use of medicines, a cornerstone principle of pharmacotherapy advanced by WHO in 1985. This irrational use of drugs is cause for concern because some of them are associated with serious heart disorders and deaths.

Contemporary narrative review of treatment options for COVID‐19

“…8,9,147,148 Before the conclusive results of RCTs were published, the off-label use of hydroxychloroquine was common for treatment or prophylaxis during the early stage of the pandemic. [149][150][151] Similar phenomenon also existed for other drugs, which may be widely used before efficacy was confirmed. As in vitro anti-viral effects do not necessarily translate into clinical effects and off-label use of drugs may cause adverse events, it is necessary to interpret the results of cell culture and animal experiments as well as observational studies cautiously, and evaluate the efficacy and safety of candidate drugs with rigorously designed RCTs.…”

Medication of Hydroxychloroquine, Remdesivir and Convalescent Plasma during the COVID-19 Pandemic in Germany—An Ethical Analysis

“…Recommendations for the medication of hydroxychloroquine, remdesivir or COVID-19 convalescent plasma to treat COVID-19 are mainly based on in vitro studies, results from animal experiments and experience with other viral infections [ 23 , 31 ]. Positive results from in vitro research or animal experiments cannot simply be transferred to humans [ 35 ]—even in emergency situations, the major physiological differences between species need to be kept in mind. The efficacy and safety of hydroxychloroquine for COVID-19 are not yet known.…”

“…Remdesivir was originally developed for hepatitis C and was later considered for Ebola. However, remdesivir was not approved for the treatment of hepatitis C or Ebola because the drug did not meet efficacy requirements [ 35 ]. The drug can be described as a sleeping candidate [ 12 ].…”

Análise Epidemiológica E O Rastreio De Vacinação De Sarampo No Brasil Durante a Pandemia Do Novo Coronavírus (Sars-Cov-2) No Ano De 2020

“…Os medicamentos como os inibidores da neuraminidase viral; inibidores da protease; antimaláricos e anti-helmínticos, passaram a ser frequentemente prescritos tanto para tratamento como para profilaxia, embora sejam eficazes e seguros frente a sua finalidade terapêutica original, em casos de infecções por SARS-CoV-2, as pesquisas são insuficientes ou revelam riscos devido à necessidade de elevadas doses para uma resposta eficaz (PAUMGARTTEN et al, 2020). Desta forma, foi possível agrupar os principais problemas relacionados ao tratamento da COVID-19 desses fármacos na Tabela 2.…”