NIH Updates Guidelines for Treating COVID-19 in Outpatients

With fewer monoclonal antibody treatments active against the Omicron variant than had previously been authorized for emergency use (see Contagion report on the Food and Drug Administration (FDA) rescinding those authorizations), the NIH has updated its guidelines for treating outpatients with mild-to-moderate COVID-19 to recommend several direct-acting antivirals.

The guidelines panel indicates its preference for ritonavir-boosted nirmatrelvir (Paxlovid, Pfizer) in most high-risk outpatients with mild-to-moderate symptoms. If that product is not available, or cannot be used because of drug interactions, it next recommends sotrovimab (GSK).

If neither of those products are available or are contraindicated, the panel recommends remdesivir (Veklury, Gilead), which was approved for outpatient and pediatric use by the FDA on January 21, in a supplement to the New Drug Application (NDA). The panel indicates that molnupiravir (Lagevrio, Merck) should only be administered when the other 3 options are unavailable or cannot be used.

Absent comparative clinical trials, the panel based its preference for ritonavir-boosted nirmatrelvir on data from the EPIC-HR trial, in which the product reduced the risk of hospitalization or death by 88% compared to placebo in outpatients with laboratory-confirmed SARS-CoV-2 infection. The panel notes that this efficacy is comparable to that reported for sotrovimab and remdesivir, and significantly greater than that of molnupiravir. It cautions, however, that ritonavir-boosted nirmatrelvir has potential for significant drug interactions, and so advises that it may not be a safe choice for all patients.

The panel recommended sotrovimab before remdesivir, partly on the requirement of the latter for intravenous administration on 3 consecutive days. "There may be logistical constraints to administering remdesivir in many settings," the panel indicated, "but it is an option if ritonavir-boosted nirmatrelvir and sotrovimab are not available."

Molnupiravir ranked last among the recommendations, based on a reported approximate 30% rate of reduced hospitalization or death, compared to approximately 80% with the other recommended agents. The panel also notes that the FDA emergency use authorization of molnupiravir warns of its potential reproductive toxicity and recommends women of child-bearing potential abstain from sex, or use reliable contraception for the duration of therapy and up to 4 days after receiving molnupiravir.Men are advised to abstain or use reliable contraception for at least 3 months after the last dose.

Although molnupiravir is not recommended for pregnant patients, the panel weighs that against the risk of severe COVID-19."When preferred therapies are not available, pregnant people who are at high risk of progressing to severe disease may reasonably choose molnupiravir therapy after being fully informed of the risks..."

"It should be noted that a number of factors affect the selection of the best treatment option for a specific patient," the guidelines panel indicates. "These factors include, but are not limited to, the clinical efficacy of the treatment option, the availability of the treatment option, the feasibility of administering parenteral medications, the potential for significant drug-drug interactions, and the regional prevalence of the Omicron VOC (variant of concern)."

The guidelines describe the mechanisms of action for the recommended agents, summarize data from the key clinical trials, and provide dosing regimens.It emphasizes that the update was required since the December 30 release, due to Omicron becoming dominant across the US.