SARS-CoV-2 infection is challenging countries and their health systems as the greatest public health emergency of international concern ever declared ¹1. Gostin LO. The great coronavirus pandemic of 2020 - 7 critical lessons. JAMA 2020; 324:1816-7.. The heavy loss of life adds to the difficulties in managing the disease, still without an effective treatment available.

Since the beginning of the pandemic, many drugs already used in other diseases have been proposed as possible therapies for COVID-19, the so-called “repositioned” drugs, including chloroquine and its byproduct hydroxychloroquine, ivermectin, nitazoxanide, remdesivir, and azithromycin. However, nearly a year after the pandemic, there is no scientific evidence to back the use of these drugs in either the prevention or treatment of COVID-19 ²2. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of Covid-19 - final report. N Engl J Med 2020; 383:1813-26.^,33. Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LCP, Veiga VC, Avezum A, et al. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med 2020; 383:2041-52.^,44. Horby P, Mafham M, Linsell L, Bell JL, Staplin N, Emberson JR, et al. Effect of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med 2020; 383:2030-40.^,55. Mitjà O, Corbacho-Monné M, Ubals M, Alemany A, Suñer C, Tebé C, et al. A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19. N Engl J Med 2020; (Online ahead of print).^,66. Siemieniuk RAC, Bartoszko JJ, Ge L, Zeraatkar D, Izcovich A, Kum E, et al. Drug treatments for covid-19 living systematic review and metanalysis. BMJ 2020; 370:m2980..

Countries that initially saw a hope for cure in some of these drugs have now eliminated them from their protocols ⁷7. Centers for Disease Control and Prevention. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html (acessado em 14/Dez/2020).
https://www.cdc.gov/coronavirus/2019-nco... . In June 2020, the U.S. government suspended the emergency use authorization that had allowed chloroquine phosphate and hydroxychloroquine sulfate to be used for treating hospitalized patients with COVID-19, outside of clinical trials. The note issued by the Food and Drug Administration (FDA) said that the possible benefits attributed to chloroquine and hydroxychloroquine failed to compensate for the known risks of their use ⁸8. U.S. Food and Drug Administration. Coronavirus (COVID-19) update: FDA revokes emergency use authorization for chloroquine and hydroxychloroquine. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and (acessado em 12/Dez/2020).
https://www.fda.gov/news-events/press-an... .

Even in this scenario, the position by the Brazilian government was to encourage the drugs’ use, lauding chloroquine and hydroxychloroquine as the “silver bullet” against COVID-19. Ministry of Health protocols still in force include these drugs as indications for the management of patients with mild, moderate, and severe symptoms and in the various phases of COVID-19’s clinical evolution ⁹9. Ministério da Saúde. Nota Informativa nº 17/2020- SE/GAB/SE/MS. Orientações do Ministério da Saúde para manuseio medicamentoso precoce de pacientes com diagnóstico da Covid-19. http://antigo.saude.gov.br/images/pdf/2020/August/12/COVID-11ago2020-17h16.pdf (acessado em 12/Dez/2020).
http://antigo.saude.gov.br/images/pdf/20... .

Promotion of the use of chloroquine and hydroxychloroquine had various consequences. A study by the Federal Council of Pharmacy compared the sales of drugs and food supplements from January to March 2019 with those of 2020, showing a 68% increase in hydroxychloroquine sales in this period ¹⁰10. Conselho Federal de Farmácia. Levantamento mostra como o medo da Covid-19 impactou venda de medicamentos. https://www.cff.org.br/noticia.php?id=5747 (acessado em 12/Dez/2020).
https://www.cff.org.br/noticia.php?id=57... . As a result, there was a widespread shortage of this drug in pharmacies, harming patients that depended on it for other health conditions ¹¹11. Conselho Nacional de Saúde. CNS recomenda ao Ministério da Saúde plano de abastecimento de cloroquina para pacientes com doenças crônicas e patologias. http://conselho.saude.gov.br/ultimas-noticias-cns/1323-cns-recomenda-ao-ministerio-da-saude-plano-de-abastecimento-de-cloroquina-para-pacientes-com-doencas-cronicas-e-patologias (acessado em 12/Dez/2020).
http://conselho.saude.gov.br/ultimas-not... .

In late May 2020, the Brazilian Federal Government announced that it had received a donation of two million doses of hydroxychloroquine from the United States ¹²12. Verdélio A. Brasil recebe 2 milhões de doses de hidroxicloroquina dos EUA. Agência Brasil 2002; 1 jun. https://agenciabrasil.ebc.com.br/politica/noticia/2020-06/brasil-recebe-dois-milhoes-de-doses-de-hidroxicloroquina-dos-eua.
https://agenciabrasil.ebc.com.br/politic... ^,1313. Ministério das Relações Exteriores. Nota à imprensa nº 62. Declaração conjunta dos governos da República Federativa do Brasil e dos Estados Unidos da América relativa à cooperação em saúde. https://www.gov.br/mre/pt-br/canais_atendimento/imprensa/notas-a-imprensa/declaracao-conjunta-dos-governos-da-republica-federativa-do-brasil-e-dos-estados-unidos-da-america-relativa-a-cooperacao-em-saude-2 (acessado em 12/Dez/2020).
https://www.gov.br/mre/pt-br/canais_aten... . The donation coincided with the abandonment of the drug’s use for treating COVID-19 in the United States. It was received by the Brazilian Army’s Chemical and Pharmaceutical Laboratory, adding to the amount already produced by that agency ¹⁴14. Exército Brasileiro. Laboratório químico farmacêutico do exército intensifica a produção de cloroquina. https://www.eb.mil.br/web/noticias/noticiario-do-exercito/-/asset_publisher/MjaG93KcunQI/content/id/11267194 (acessado em 12/Dez/2020).
https://www.eb.mil.br/web/noticias/notic... . This investment by the Brazilian government became the object of an investigation by the Federal Accounts Court ¹⁵15. Tribunal de Contas da União. Processo 039.440/2020-6. https://pesquisa.apps.tcu.gov.br/#/push/processo?numero=039.440%2F2020-6 (acessado em 12/Dez/2020).
https://pesquisa.apps.tcu.gov.br/#/push/... and was also questioned by the Chamber of Deputies, due to the amount spent on producing a drug with no scientific evidence in COVID-19, potentially violating the principle of efficiency in the public administration ¹⁶16. Câmara dos Deputados. Requerimento de informação nº 1.194, de 2020. Diário da Câmara dos Deputados. http://imagem.camara.gov.br/Imagem/d/pdf/DCD0020200925001680000.PDF#page= (acessado em 12/Dez/2020).
http://imagem.camara.gov.br/Imagem/d/pdf... .

A report that analyzed misinformation patterns among countries during the pandemic showed through hypergeometric and qualitative analyses that Brazil leads the world in terms of drug-related misinformation. Brazil has continued to cite chloroquine and hydroxychloroquine as possible treatments throughout the pandemic, indicating that the scientific evidence is not being adequately captured by the country’s public debate ¹⁷17. Machado CCV, Santos JG, Santos N, Bandeira L. International trends in misinformation and the departure from the scientific debate. https://laut.org.br/wp-content/uploads/2020/11/Political-Self-Isolation-vF.pdf (acessado em 12/Dez/2020).
https://laut.org.br/wp-content/uploads/2... . This fact bears a strong relationship to the stance by government authorities and agencies, like the Ministry of Health itself, revealing misinformation as a tactic tied closely to the country’s domestic political disputes.

In Brazil, the defense of “early treatment” based on chloroquine/hydroxychloroquine and other drugs has become a symbol of political bias in dealing with the epidemic. The alternative provided by the Brazilian government involves the supply of the so-called “kit-covid” in primary healthcare services and adopted by some Brazilian municipalities aligned with the Federal Government’s premise ¹⁸18. Celestino C. Centro de Triagem entregou mais de 12 mil kits de medicamentos para tratamento da Covid-19. Governo do Mato Grosso - Notícias 2020; 2 set. http://www.mt.gov.br/-/15304126-centro-de-triagem-entregou-mais-de-12-mil-kits-de-medicamentos-para-tratamento-da-covid-19.
http://www.mt.gov.br/-/15304126-centro-d... . “Kit-covid” consists of a range of combinations that invariably include chloroquine/hydroxychloroquine, azithromycin, ivermectin, and other drugs, depending on the location. The Federal Government is now also signaling the availability of “kit-covid” in pharmacies included in agreements with the Popular Pharmacy Program of Brazil (PFPB) ¹⁹19. Vargas M. Saúde prevê gastar R$ 250 milhões para distribuir "kit covid". O Estado de S. Paulo 2002; 11 dez. https://saude.estadao.com.br/noticias/geral,saude-preve-gastar-r-250-milhoes-para-por-kit-covid-em-farmacias-populares,70003547892.
https://saude.estadao.com.br/noticias/ge... .

The PFPB was originally created to expand access to medicines in the country, targeting the most prevalent health conditions and the lower-income population. According to estimates, notwithstanding criticisms over budget fund transfers to the private sector (to the detriment of public investment), the Program succeeded in achieving its purpose according to the principles of the National Pharmaceutical Services Policy and the National Medicines Policy. The Program covered a large contingent of users and displayed great diffusion in the country’s territory, through the government’s own pharmacies and private pharmacies under the above-mentioned agreement ²⁰20. Santos-Pinto CDB, Costa NR, Osório-de-Castro CGS. Quem acessa o Programa Farmácia Popular do Brasil? Aspectos do fornecimento público de medicamentos. Ciênc Saúde Colet 2011; 16:2963-73.^,2121. Silva RM, Caetano R. Programa "Farmácia Popular do Brasil": caracterização e evolução entre 2004-2012. Ciênc Saúde Colet 2015; 20:2943-56..

In the initial stage of the COVID-19 pandemic, the PFPB, in keeping with social distancing rules, organized to expand the amounts per patient of the Program’s drugs that were authorized for dispensing, besides facilitating drug pickup by third parties (e.g., patients’ family members), aimed at decreasing the circulation of persons, especially those belonging to risk groups ²²22. Ministério da Saúde. Alterações no programa farmácia popular devido à situação de emergência de saúde pública decorrente do coronavírus (covid19). https://antigo.saude.gov.br/noticias/assistencia-farmaceutica/46583-alteracoes-no-programa-farmacia-popular-devido-a-situacao-de-emergencia-de-saude-publica-decorrente-do-coronavirus-covid19 (acessado em 14/Dez/2020).
https://antigo.saude.gov.br/noticias/ass... . However, in December 2020, the PFPB appeared in the media again due to the possibility that it was dispensing “kit-covid” ¹⁹19. Vargas M. Saúde prevê gastar R$ 250 milhões para distribuir "kit covid". O Estado de S. Paulo 2002; 11 dez. https://saude.estadao.com.br/noticias/geral,saude-preve-gastar-r-250-milhoes-para-por-kit-covid-em-farmacias-populares,70003547892.
https://saude.estadao.com.br/noticias/ge... .

This is not the first time that the PFPB has played a role during health emergencies. Oseltamivir phosphate (Tamiflu), used in the treatment of H1N1 influenza, began to be dispensed by the PFPB in April 2010 ²³23. Ministério da Saúde. Portaria nº 367, de 22 de fevereiro de 2010. Inclui o medicamento Fosfato de Oseltamivir no Programa Farmácia Popular do Brasil - Aqui Tem Farmácia Popular, e define os valores de referência para as suas apresentações. Diário Oficial da União 2010; 23 fev.. The Institute of Drug Technology, Oswaldo Cruz Foundation (Farmanguinhos/Fiocruz) was responsible for the drug’s production, based on the active pharmaceutical ingredient the Ministry of Health had in its inventory. All the Program’s own units - some 530 at the time - supplied the drug, totaling more than two million treatments for patients with flu symptoms ²⁴24. Fundação Oswaldo Cruz. Farmácia Popular oferece remédio contra gripe H1N1. https://portal.fiocruz.br/noticia/farmacia-popular-oferece-remedio-contra-gripe-h1n1 (acessado em 14/Dez/2020).
https://portal.fiocruz.br/noticia/farmac... . Oseltamivir was also supplied by private pharmacies under the agreement mentioned above, subsidized by the government. The Ministry of Health also recommended that state and municipal health secretariats should decentralize their reserves of the drug in order to facilitate immediate access ²⁵25. Organização Pan-Americana da Saúde. Ministério da Saúde informa que a utilização oportuna do oseltamivir reduz risco de óbito por influenza A (H1N1). https://www.paho.org/bra/index.php?option=com_content&view=article&id=3455:ministerio-da-saude-informa-que-a-utilizacao-oportuna-do-oseltamivir-reduz-risco-de-obito-por-influenza-a-h1n1-3&Itemid=812 (acessado em 14/Dez/2020).
https://www.paho.org/bra/index.php?optio... . The drug’s indication, which had been approved in the country, determined that oseltamivir should only be used in patients with symptoms of severe respiratory illness and with onset of the symptoms in the previous 48 hours.

There was an initial moment of panic at the time, along with the product’s mass advertising by industry. Thus, oseltamivir, which the scientific community later showed to have limited efficacy for treating H1N1, was turned into an object of desire for persons with any suspicious symptoms ²⁶26. Gupta YK, Meenu M, Mohan P. The Tamiflu fiasco and lessons learnt. Indian J Pharmacol 2015; 47:11-6., increasing the volume of prescriptions. The drug’s dispensing throughout Brazil in the PFPB units, sponsored by the Federal Government, provided an opportunity for a discussion on the quality of this use and its appropriation by the Program for distribution of the drug’s reserves.

With the COVID-19 pandemic, the use of the Popular Pharmacy has been proposed again to promote drug distribution. However, this time there is no evidence of efficacy and safety benefits for the disease in question, while there is clear evidence of potential risks. The use of chloroquine and its byproducts can aggravate the clinical status of patients with prior cardiac disease ²⁷27. Borba MGS, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, Brito M, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial. JAMA Netw Open 2020; 3:e208857.. There are also other issues involving the prescription and dispensing of drugs for uses not approved by the regulatory agency, further expanding the health risks related to the pandemic.

Off-label use, by definition, is not authorized by the regulatory agency, but it is often absolutely necessary when the procedures for authorization fail to keep pace with the evidence of benefit, or when the lack of clinical trials in some patient groups prevents the indication that is deemed safe and potentially effective in those groups ²⁸28. Paumgartten FJR, Oliveira ACAX. Uso off label, compassivo e irracional de medicamentos na pandemia de Covid-19, consequências para a saúde e questões éticas. Ciênc Saúde Coletiva 2020; 25:3413-9..

Off-label use of chloroquine and hydroxychloroquine was admitted at the beginning of the pandemic, when there were still hypotheses concerning its efficacy in COVID-19. The position taken by the Federal Council of Medicine was that the prescribed use of these drugs in COVID-19 could result from agreement between physician and patient ²⁹29. Conselho Federal de Medicina. Parecer CFM nº 4/2020. https://sistemas.cfm.org.br/normas/visualizar/pareceres/BR/2020/4 (acessado em 16/Dez/2020).
https://sistemas.cfm.org.br/normas/visua... . However, this position has been seriously shaken since the publication of consensus statements by specialists in Brasil ³⁰30. Sociedade Brasileira de Infectologia. Atualizações e recomendações sobre a COVID-19. https://infectologia.org.br/wp-content/uploads/2020/12/atualizacoes-e-recomendacoes-covid-19.pdf (acessado em 16/Dez/2020).
https://infectologia.org.br/wp-content/u... ^,3131. Associação de Medicina Intensiva Brasileira. Diretrizes para o tratamento farmacolo´gico da COVID-19. https://www.amib.org.br/fileadmin/user_upload/amib/2020/maio/19/Diretrizes_para_o_Tratamento_Farmacologico_da_COVID_-_v18mai2020__2_.pdf (acessado em 16/Dez/2020).
https://www.amib.org.br/fileadmin/user_u... ^,3232. Falavigna M, Colpani V, Stein C, Azevedo LC, Bagattini AM, Brito GV, et al. Diretrizes para o tratamento farmacológico da COVID-19. Rev Bras Ter Intensiva 2020; 32:166-96.^,3333. National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. https://www.covid19treatmentguidelines.nih.gov/whats-new/ (acessado em 16/Dez/2020).
https://www.covid19treatmentguidelines.n... and studies pointing to the lack of clinical benefit from these drugs ³3. Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LCP, Veiga VC, Avezum A, et al. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med 2020; 383:2041-52.^,44. Horby P, Mafham M, Linsell L, Bell JL, Staplin N, Emberson JR, et al. Effect of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med 2020; 383:2030-40.^,55. Mitjà O, Corbacho-Monné M, Ubals M, Alemany A, Suñer C, Tebé C, et al. A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19. N Engl J Med 2020; (Online ahead of print)., further increasing the questioning of persistent prescription and dispensing of these drugs for COVID-19.

Pharmaceutical Services, an integral and essential component of the Brazilian health system, is responsible for making medicines available to the population, prioritizing the principles of safety and efficacy and always with rational use as part of its activities. In a pandemic scenario, with uncertainties surrounding the use of medicines, pharmaceutical counseling is more necessary than ever. The PFPB today, unlike at the moment of the H1N1 epidemic, is represented exclusively by drug retail. In private pharmacies, dispensing can be done by individuals without technical training or the requirement to provide clarifications and counsel patients on the rational use of medicines ³⁴34. Conselho Federal de Farmácia. Dados 2019. https://www.cff.org.br/pagina.php?id=801&titulo=Dados+2018 (acessado em 16/Dez/2020).
https://www.cff.org.br/pagina.php?id=801... . Thus, what are the expected results of the unmonitored supply of drugs in the “kit-covid” by the PFPB?

The possibility of the Brazilian government using the PFPB as a repository and distributor of drugs that are devoid of evidence of efficacy and safety may first cause a waste of public funds for distribution of the drugs and for reimbursing the possible operational costs incurred by private pharmacies. Such funds could be redirected to effective activities in response to the pandemic. Second, the most worrisome point is the Brazilian population’s exposure to inadmissible risks, potentially related to the nonrational use of these drugs.

We are thus witnessing the subversion of the PFPB’s role by the Brazilian government, which appears to place its political agenda ahead of the population’s health priorities and wellbeing.

References

Publication Dates

History