Besides vaccines, one of the most effective weapons in the fight against COVID-19 is Paxlovid, an antiviral pill treatment combining the drugs nirmatrelvir and ritonavir. Studies have found that Paxlovid can reduce the risk of COVID-19-related hospitalization or death in high-risk adults with mild or moderate disease by 89 percent compared with placebo.
Paxlovid is still relatively new — the U.S. Food and Drug Administration (FDA) authorized this therapy for emergency use in December 2021 — so you may be wondering how it works, who should take it, and what side effects to expect.
Answering these and other FAQs are two infectious disease specialists: William Schaffner, MD, a professor of preventive medicine and health policy at the Vanderbilt University School of Medicine in Nashville, Tennessee; and Prasanna Jagannathan, MD, assistant professor of medicine and of microbiology and immunology at Stanford University in Palo Alto, California.
What is Paxlovid, and how does it work?
Paxlovid is a drug regimen developed by Pfizer for people 12 and older who have mild to moderate COVID-19 and are at high risk of becoming severely sick or dying, per the FDA fact sheet (PDF). Patients take three pills — two tablets of nirmatrelvir and one tablet of ritonavir, packaged together — twice daily for five days.
Nirmatrelvir is specifically designed to block the activity of an enzyme that the coronavirus needs to replicate, and ritonavir slows down nirmatrelvir’s breakdown to help it remain in the body for a longer period of time at a higher concentration, per the FDA.
When should you start taking Paxlovid?
If you’re eligible, you should begin taking Paxlovid no more than five days after symptoms begin.
“Paxlovid prevents the virus from multiplying more and spreading throughout your body and making you sick,” said Dr. Schaffner. “Of course, in order for that to work, we have to get in there early. So as soon as you test positive, you should start treatment.”
Who is eligible to take Paxlovid?
Only individuals in COVID-19 high-risk groups with mild or moderate coronavirus infection should take Paxlovid. The Centers for Disease Control and Prevention (CDC) defines a high-risk person as someone who is more likely to be hospitalized, die, or need intensive care or a ventilator to help breathe. Those in the high-risk category include adults 65 and older and those with underlying medical conditions, notes the CDC.
“if you’re a smoker, if you’re immunocompromised, if you’re an organ transplant recipient, if you’re overweight or obese, if you have hypertension, if you have diabetes, if you have kidney disease — those are some of the many examples of comorbidities that are predictive of having a worst outcome if you are infected,” says Dr. Jagannathan.
Should people who aren’t at high risk take Paxlovid?
Pfizer released study results showing that for standard-risk patients, who are usually able to recover from COVID-19 without treatment, Paxlovid provides little benefit.
Does Paxlovid have any side effects?
Side effects of Paxlovid are mild and relatively infrequent, according to research from Pfizer. In a study involving close to 2,000 people, about 1 in 5 had a so-called adverse event (usually mild) whether receiving Paxlovid or placebo. These include diarrhea, muscle aches, and elevated blood pressure.
In one study, almost 6 percent of those who took Paxlovid described having dysgeusia, an altered or impaired sense of taste.
“Some have described a kind of chalky-like taste in the mouth — I’ve heard that described fairly commonly,” says Jagannathan. Other patients have described having a bitter or metallic taste in the mouth, a side effect dubbed Paxlovid mouth.
“But other than that, I think it’s really well tolerated,” Jagannathan adds.
Is there anyone who should not take Paxlovid?
Paxlovid can have harmful interactions with a number of other medications, so it’s important to discuss any drugs you’re taking with a physician or pharmacist before beginning treatment.
There can be different strategies for managing these drug interactions. For instance, patients can temporarily stop taking the cholesterol-lowering medication atorvastatin (Lipitor) while on Paxlovid and then resume after finishing the five-day course. With other medications, the doctor might recommend lowering the dose of the drug with careful monitoring while the patient takes Paxlovid.
The National Institutes of Health provides a comprehensive list of medications that do and do not cause interactions.
The FDA says that Paxlovid is not recommended for people with severe renal (kidney) or liver impairment. Physicians also need to be cautious when prescribing Paxlovid to patients with preexisting liver diseases, liver enzyme abnormalities, or liver inflammation, as ritonavir may cause liver damage.
People who can’t take Paxlovid may be able to take the oral antiviral pill treatment molnupiravir (Lagevrio) by Merck. A review by the FDA (PDF) found molnupiravir to be 30 percent effective at reducing the likelihood of hospitalization in high-risk COVID-19 patients.
Other treatment options authorized by the FDA are remdesivir (Veklury) and the monoclonal antibody therapy bebtelovimab. Both are administered via IV at outpatient infusion centers — generally at hospitals or medical centers.
What is Paxlovid rebound?
Anthony Fauci, MD, the chief medical advisor to President Joe Biden, made news when he took Paxlovid for COVID-19 in June 2022 and tested negative after finishing treatment, only to test positive again a few days later, per a story in The New York Times. His is one of many anecdotal reports detailing a phenomenon known as Paxlovid rebound.
Studies have shown that Paxlovid rebound is relatively uncommon. An analysis published in the journal Clinical Infectious Diseases of 483 high-risk patients who received Paxlovid at a time when omicron was dominant found that just four patients (0.8 percent) experienced a “rebound” of symptoms, which were generally mild, at a median of nine days after treatment. All symptoms improved without additional COVID-19 therapy.
Another study, posted on medRxiv (which has not yet been peer-reviewed), involving more than 11,000 patients who took Paxlovid, found that rebound rates at 7 and 30 days after Paxlovid treatment were 3.53 percent and 5.4 percent for COVID-19 infection, and 2.31 percent and 5.87 percent for COVID-19 symptoms. A very small percentage — less than 1 percent — were later hospitalized.
“What is happening in some people is their own immune response hasn’t built up quite enough at the end of the five days of Paxlovid, and the virus starts multiplying again, but usually, in a minor way that causes relatively minor illness,” says Schaffner.
As Dr. Fauci noted to reporters, despite the rebound, Paxlovid “did what it was supposed to do” — keep him out of the hospital.
How can I get Paxlovid?
Paxlovid is available by prescription from a doctor. Patients can also get it at a location in the national government’s Test-to-Treat program, where an on-site nurse practitioner or physician assistant can authorize the medication.
In early July the FDA expanded access to Paxlovid by allowing state-licensed pharmacists to prescribe it to eligible patients. If you test positive at a pharmacy clinic and qualify for treatment, you can fill the prescription then and there.
This policy change has the potential to open up access to Paxlovid at hundreds of thousands of pharmacies across the country.
If Paxlovid works so well, why bother getting vaccinated?
Vaccines are highly effective at preventing severe illness, so it’s best to take advantage of that protection and do all you can to avoid getting COVID-19 in the first place.
“Not getting vaccinated and depending on just Paxlovid to help would be a bit like playing viral roulette,” Schaffner says. “Besides, the vaccine has been given to many millions of people now and it’s been shown to be really very safe.”