Although majority of COVID-19 cases present as mild to moderate disease which can be managed at home simply with over-the-counter medicines, more severe disease states require specialised medical intervention. Early on in the battle against this global pandemic, one of the most commonly used drugs for treatment of COVID-19 was remdesivir. However, being an injectable renders it difficult to be used in a domestic setup, limiting its utility. Thus, the availability of oral drugs is a major step forward in increasing accessibility of treatment to many at risk for severe disease.
What are the different oral drugs available for COVID-19 treatment?
Designed and manufactured by India-based Glenmark Pharmaceuticals, Favipravir has been approved for use to treat mild to moderate Covid-19 in the three most populous Asian countries – China, India and Indonesia. Originally developed and approved for treatment of influenza in Japan in the year 2014, the drug has been repurposed for treatment of COVID-19 infection.
Favipravir acts by interfering with viral replication. Robust data for efficacy in COVID-19 treatment is lacking, with recent trials in the US, Mexico and Brazil failing to show any significant benefit on clinical recovery from COVID-19 late last year.
Paxlovid was granted Emergency Use Authorisation (EUA) by U.S. FDA on 22nd December 2021 for treatment of mild to moderate COVID-19 disease in adults and children ≥12 years of age who are at high risk for progression to severe disease.
The clinical trials conducted by Pfizer revealed that when taken within five days of onset of symptoms, Paxlovid reduced risk of hospitalisation or death in COVID-19 patients by 88%. Notably, in vitro studies have demonstrated efficacy against the Omicron variant.
Paxlovid is a combination of two antivirals, nirmatrelvir and ritonavir. Nirmatrelvir interferes with the ability of SARS-CoV-2 to replicate, while ritonavir retards breakdown of nirmatrelvir for enhanced efficacy.
Paxlovid is administered as three tablets (two tablets of nirmatrelvir 150mg and one tablet of ritonavir 100mg) taken together orally twice daily for five days. Common side effects include impaired taste, diarrhoea, vomiting, hypertension, muscle pain and chills.
Molnupiravir is an oral antiviral drug manufactured by Merck & Ridgeback Biotherapeutics for COVID-19 treatment. The drug was granted EUA by FDA on 23rd December 2021, for treatment of mild to moderate COVID-19 disease in adults ≥18 years of age. Molnupiravir reduces risk of hospitalization and death in COVID-19 patients by 30%. In vitro studies have demonstrated efficacy against the Omicron variant.
Molnupiravir acts by interfering with viral replication. Likewise, it should be taken within five days of onset of symptoms. The recommended dose for Molnupiravir is 800 mg (four 200 mg capsules) taken orally every 12 hours for five days, with or without food. The common side effects of the drug include dizziness, nausea and diarrhea.
Baricitinib was approved (as monotherapy) for emergency use by U.S FDA on 29th July 2021 for treatment of severe or critical COVID-19 disease in hospitalised adults and pediatric patients ≥2 years of age requiring supplemental oxygen, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). It is also one of two drugs recommended by WHO on 14th January 2022 for COVID-19 treatment.
Clinical trials have suggested that baricitinib vs placebo improves survival rate and reduces the need for ventilation, with no observed meaningful differences in rates of adverse reactions. The efficacy of drug against Omicron variant is not clear at present.
Originally FDA-approved in 2018 for the treatment of rheumatoid arthritis, the immunosuppressant works by inhibiting Janus Kinase enzymes which cause inflammation and tissue damage seen in severe COVID-19 infections.
Baricitinib is administered orally once daily, for 14 days or until hospital discharge (whichever comes first), at a dose of 4mg for patients ≥9 years of age and 2mg for patients ≥2 years to less than 9 years of age. Possible side effects may include blood clots, serious infections and laboratory anomalies (liver function tests, blood cell counts).
Efficacy of current oral drugs against Omicron variant
At present, results from in-vitro studies of oral drugs against Omicron have been promising. With the rapidly evolving SARS-CoV-2 and highly transmissible mutant variants emerging, more in-vivo trials in the real-world setting have to be conducted expediently. Convenient storage and administration of oral drugs vs injectables will extend accessibility of treatment and bolster the arsenal against this devastating virus.