FDA: The Wait for COVID Pills Is Over

Oral antiviral treatment for COVID-19 is now on the table following FDA’s emergency use authorization (EUA) for nirmatrelvir/ritonavir (Paxlovid), the agency announced on Wednesday.

Paxlovid is authorized for use in adults and pediatric patients with mild-to-moderate COVID-19 who are at high risk of progressing to severe illness. It is administered as three pills (two of nirmatrelvir and one of ritonavir) twice daily for 5 days, for a total of 30 pills, the agency said.

However, the FDA added that the drug is only available by prescription, must be given within 5 days of symptom onset and is not authorized for use longer than 5 days.

Importantly, the FDA said the drug is not meant as a substitute for vaccination for those where vaccines and boosters are indicated, nor is it authorized for pre-exposure or post-exposure prophylaxis.

“This authorization provides a new tool to combat COVID-19 at a crucial time in the pandemic as new variants emerge and promises to make antiviral treatment more accessible to patients who are at high risk for progression to severe COVID-19,” said Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research in an FDA statement.

Paxlovid’s problem, however, is insufficient production by manufacturer Pfizer: the company revealed that there are only 180,000 treatment courses available, and another 80 million expected by the end of 2022. The Biden administration has already claimed 10 million courses of the pills.

Experts worried about supplies for the rest of the world are calling for other companies to join in the manufacturing of the drug.

In the EPIC-HR trial, Paxlovid was found to cut COVID hospitalizations and deaths by nearly 90% in high-risk patients in interim results announced in November; this was confirmed in final data from the phase II/III trial released in mid-December. The trial of more than 2,200 people saw no deaths in the Paxlovid arm and 12 in the placebo arm through day 28.

Side effects of Paxlovid include sense of taste, diarrhea, high blood pressure and muscle aches, and the FDA added that it may cause interactions with other drugs and HIV drug resistance among people living with undiagnosed or uncontrolled HIV.

Because ritonavir may cause liver damage, the agency urged caution when administering the drug to those with pre-existing liver diseases, liver abnormalities or liver inflammation.

The drug is contraindicated for patients already taking drugs that either are “highly dependent” on the enzymes Paxlovid inhibits “for metabolism and for which elevated concentrations of certain drugs are associated with serious and/or life-threatening reactions,” and those taking drugs that induce the same enzymes as Paxlovid inhibits, the FDA said.

Paxlovid is not recommended for those with severe liver or kidney impairment, the agency added, and a healthcare provider should be consulted prior to use.

The FDA did not convene its Antimicrobial Drugs Advisory Committee (AMDAC) prior to this EUA, the way they did for molnupiravir in late November. That drug was ultimately recommended by a divided committee by a vote of 13-10, but has yet to be authorized.

Last Updated December 22, 2021