TWO ORAL THERAPIES NOW AVAILABLE TO TREAT OUTPATIENT COVID
December 28, 2021 - The FDA granted emergency use authorization to two oral therapies for the outpatient treatment of COVID. Both drugs are recommended for people at high risk for severe COVID (see high-risk criteria), and they should be taken within 5 days of symptom onset.
Paxlovid is a therapy from Pfizer that contains two medications - nirmatrelvir and ritonavir. Nirmatrelvir is a protease inhibitor that inhibits COVID replication. Ritonavir, which has no activity against COVD, is included to block the metabolism of nirmatrelvir and boost its exposure. Unfortunately, ritonavir can also block the metabolism of many other drugs, and Paxlovid has a long list of drug interactions (the University of Liverpool has published a website that offers guidance on Paxlovid drug interactions. See University of Liverpool COVID-19 drug interactions for more). In its pivotal trial, 2246 high-risk patients with laboratory-confirmed COVID were treated with Paxlovid or placebo within 5 days of symptom onset. The incidence of hospitalization or death at 28 days was 0.7% in Paxlovid-treated patients and 6.5% in placebo-treated patients. There were no deaths in the Paxlovid group and 9 in the placebo group. Paxlovid is approved for adults and children 12 years of age and older who weigh 88 pounds or more.
Molnupiravir is an antiviral drug from Merck that has a novel mechanism of action. It works by mimicking the nucleic acids that COVID uses to produce new RNA. When COVID uses molnupiravir, a sort of fake nucleic acid, errors accumulate in the RNA, and viral replication is blocked. In its pivotal trial, Molnupiravir was compared to placebo in 1433 unvaccinated, high-risk adults with laboratory-confirmed COVID and symptom onset within 5 days. The incidence of hospitalization or death at 29 days was 6.8% in Molnupiravir-treated patients and 9.7% in placebo-treated patients. There was one death in the Molnupiravir group and 9 in the placebo group. Molnupiravir should not be given to pregnant women and people under the age of 18. It also has the unusual precaution that men should not impregnate women for 3 months after use.
Until now, the only outpatient treatment for COVID was antibody infusions that have limited availability and require a visit to a healthcare facility. Once Molnupiravir and Paxlovid become widely available, they should have a significant impact on COVID hospitalizations and death.