Two oral antivirals receive FDA authorization for COVID-19 treatment

USA: As the number of Omicron cases continues to increase in India and worldwide, two recently approved antiviral pills could be a game-changer for the most vulnerable. However, the experts have cautioned that the new medications may not be safe for everyone and might require careful monitoring by doctors and pharmacists. 

The U.S. Food and Drugs Administration (FDA) has recently given approval for Emergency Use Authorisation (EUA) to two drugs to be used in certain patients. The drugs are described are -- Molnupiravir, developed by Merck and Ridgeback Biotherapeutics for treating mild-to-moderate COVID-19 in adults who are at risk for severe disease, and Paxlovid, developed by Pfizer Inc for treating mild-to-moderate Covid-19 in adults and children 12 years and older, who are likely to be at greater risk for severe infection. 

Both treatments are available by prescription only and should be initiated as soon as possible after a diagnosis of COVID-19 and within five days of symptom onset.

About Paxlovid

Pfizer's Paxlovid is authorized for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kilograms or about 88 pounds) with positive results of direct SARS-CoV-2 testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

Paxlovid's treatment is a combination of two pills taken over five days-- the Paxlovid cocktail consists of two tablets of the antiviral nirmatrelvir and one tablet of ritonavir. However, one of the two drugs in the antiviral cocktail could result in severe or life-threatening interactions with widely used medications, including blood thinners, statins, and some antidepressants. And, Paxlovid is not recommended for people with severe kidney or liver disease.

Nirmatrelvir (Paxlovid, Pfizer) is a viral protease inhibitor with expected in vitro activity against all clinically significant SARS-CoV-2 variants to date. In an unpublished manufacturer-supported study, nirmatrelvir boosted with the CYP3A inhibitor ritonavir reduced rates of hospitalization or all-cause death by almost 90% among unvaccinated high-risk adults outpatients with confirmed mild-to-moderate COVID-19.

A study involving vaccinated standard-risk adults is ongoing. The drug has also been authorized for unvaccinated children and teens 12 and older. The dosing regimen consists of two 150-mg nirmatrelvir tablets and one 100-mg ritonavir tablet taken together twice daily for 5 days. Renal impairment requires dose reduction; patients with severe liver or kidney disease should not receive treatment. Coadministration with drugs metabolized by CYP3A or those inducing the enzyme may be dangerous. No specific adverse effects have been associated with nirmatrelvir plus ritonavir to date.

About Molnupiravir

Merck's molnupiravir is authorized for the treatment of mild-to-moderate COVID-19 in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate. 

Molnupiravir is not authorized for use in patients younger than 18 years of age because molnupiravir may affect bone and cartilage growth. It is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in patients hospitalized due to COVID-19 because the benefit of treatment has not been observed in people when treatment started after hospitalization due to COVID-19.   

Molnupiravir (Lagevrio, Merck) is a nucleoside analog that induces fatal mutations in the SARS-CoV-2 genome; it too has demonstrated in vitro activity against all clinically significant viral variants.

In a manufacturer-supported study of high-risk unvaccinated adult outpatients with mild-to-moderate COVID-19, the drug reduced rates of hospitalization or all-cause mortality by about 30%. Because of concerns about possible mutagenicity, molnupiravir is not recommended during pregnancy; and because of possible toxicity to the bone, cartilage, or both, the drug has not been authorized for children or teens younger than 18. The dose is four 200-mg capsules twice daily for 5 days. Side effects have been limited to mild decreases in hemoglobin. No renal or hepatic adjustments are necessary, and no drug-drug interactions have been identified. An FDA advisory committee also articulated concerns about the drug's potential ability to generate viral mutants of concern.

Reference:

1) Coronavirus (COVID-19) Update: FDA Authorizes Additional Oral Antiviral for Treatment of COVID-19 in Certain Adults

2) Coronavirus (COVID-19) Update: FDA Authorizes First Oral Antiviral for Treatment of COVID-19