Are new oral anti-COVID-19 drugs effective?

08 Nov 2021
Respiratory conditions
  • COVID-19
Type of resource
IPCRG COVID-19 and respiratory Q&A

What the research says:

The oral antiviral agent molnupiravir has also been approved for use in the UK (MHRA 2021). There are currently no other oral agents approved for the treatment of patients with COVID-19 in the community care setting (Siemeiniuk et al 2020). Systemic oral steroid treatment (dexamethasone, prednisolone, methylprednisolone, hydrocortisone) is recommended for in-hospital or advanced care at home of patients with COVID-19 illness (WHO 2020). Evidence is emerging that high-dose oral steroids may reduce the risk for severe hypoxia in COVID-19 illness. Oral agents with limited evidence of efficacy and under evaluation for the treatment of patients with COVID-19 in the community care setting are shown in the Table below:

aMHRA Press release. First oral antiviral for COVID-19, Lagevrio (molnupiravir), approved by MHRA. Available at: https://www.gov.uk/government/news/first-oral-antiviral-for-covid-19-lagevrio-molnupiravir-approved-by-mhra. bTardiff et al 2021; cPfizer Press Release. Available at: https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate. See also Owen et al 2021; dApproved for the treatment of influenza and currently under investigation in the PRINCIPLE Study; eApproved for the treatment of HIV infection and currently under investigation in the PRINCIPLE Study; fReis et al 2021.

What this means for your clinical practice:

  • The oral antiviral agent molnupiravir has also been approved for use in the UK for the treatment of patients with non-severe COVID-19 who are at the highest risk for hospitalisation. There are currently no other guideline-recommended oral treatments for the management of the acute COVID-19 infection in the community setting although other treatments are approved for use in this setting.
  • Medicinal treatment of acute COVID-19 should currently focus on symptomatic relief. 
    • Standard antipyretics, paracetamol or ibuprofen, can be used for the management of fever and pain, there is no evidence to suggest they halt progression to more severe disease. 
    • Diarrhoea and nausea should be managed according to local standard of care
  • Antibiotic prophylaxis is not advised and antibiotics should not be prescribed unless there is a clinical suspicion of a bacterial infection, the risk of which has been shown to be low.
  • A number of oral drugs are currently under investigation including antiviral agents, oral steroids or prophylactic oral anticoagulants for the treatment of patients with COVID-19 in the community setting.

Useful links and supporting references:

Merck and Ridgeback’s investigational oral antiviral molnupiravir reduced the risk of hospitalization or death by approximately 50 percent compared to placebo for patients with mild or moderate COVID-19 in positive interim analysis of Phase 3 study. Available at: https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/. Accessed October 2021.

Owen DR, et al. An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19. Pre-print, not yet peer reviewed, available at: https://www.medrxiv.org/content/10.1101/2021.07.28.21261232v1. Accessed October 2021.

PRINCIPLE study in community patients: https://www.principletrial.org/.Accessed October 2021.

Reis G, et al. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. Lancet Glob Health 2021;S2214-109X(21)00448-4. Available at: https://doi.org/10.1016/S2214-109X(21)00448-4. Accessed: November 2021.

Siemieniuk RAC, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ 2020;370;m2980. Available at: https://www.bmj.com/content/370/bmj.m2980. Accessed October 2021.

Tardiff JC, et al. Efficacy of colchicine in non-hospitalized patients with COVID-19. Pre-print, not yet peer reviewed, available at: https://www.medrxiv.org/content/10.1101/2021.01.26.21250494v1. Accessed October 2021.

World Health Organization. A living WHO guideline on drugs for covid-19. Available at: https://www.bmj.com/content/370/bmj.m3379. Accessed October 2021.

Authors:

Tiago Maricoto, MD, PhD (Family Doctor, Aradas Health Unit and University of Beira Interior, CACB-Clinical Academic Centre of Beiras, Portugal) for and on behalf of the IPCRG practice driven answers review group.