13 Things To Know About Paxlovid, the Latest COVID-19 Pill
Pfizer's COVID-19 pill, Paxlovid, appears to have a lot of positives, including an 89% reduction in the risk of hospitalization and death in clinical trials. Yale Medicine experts answer commonly asked questions about this COVID-19 treatment.
[Originally published: March 10, 2022. Updated: Sept. 5, 2023]
Note: Information in this article was accurate at the time of original publication. Because information about COVID-19 changes rapidly, we encourage you to visit the websites of the Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), and your state and local government for the latest information.
Paxlovid, the pill that has become the go-to treatment for COVID-19 treatment, was granted full approval in May by the Food And Drug Administration (FDA) for the treatment of mild-to-moderate COVID-19 in adults at high risk for severe disease, including hospitalization and death. The drug also remains available to everyone 12 and older (weighing at least 88 pounds) who has mild-to-moderate disease and is at high risk for severe disease under an FDA Emergency Use Authorization.
Paxlovid is an oral antiviral pill that can be taken at home to help keep high-risk patients from getting so sick that they need to be hospitalized. So, if you are eligible to take the pills, you can take them at home and lower your risk of going to the hospital.
The drug, developed by Pfizer, has a lot of positives: It had an 89% reduction in the risk of hospitalization and death in unvaccinated people in the clinical trial that supported the EUA, a number that was high enough to prompt the National Institutes of Health (NIH) to prioritize it over other COVID-19 treatments. Studies outside of the laboratory have since confirmed Paxlovid’s effectiveness among people who have been vaccinated. It’s cheaper than many other COVID-19 drugs (at this time, U.S. residents eligible for Paxlovid will continue to receive the medicine at no charge), and, perhaps most reassuring, it is expected to work against the latest Omicron subvariants.
“It's really our first efficacious oral antiviral pill for this virus,” says Scott Roberts, MD, a Yale Medicine infectious diseases specialist. “It shows clear benefit, and it really can prevent hospitalization and death in people who are at high risk.”
FDA approval will allow Paxlovid to remain available for adults indefinitely. Meanwhile, Pfizer continues to gather pediatric data to submit for FDA approval in children at a future date.
As far as convenience, this medication is considered an improvement over treatments like remdesivir (approved by the FDA in October 2020), which is administered by intravenous (IV) injection. The FDA also granted an EUA in December to a pill from Merck called molnupiravir (Lagevrio), but some studies suggest that molnupiravir has only a 30% reduction in the risk for hospitalization and death from COVID-19.
We asked Yale Medicine infectious diseases experts common questions about Paxlovid. Below are their responses.
1. How does Paxlovid work?
Paxlovid is an antiviral therapy that consists of two separate medications packaged together. When you take your three-pill dose, two of those pills will be nirmatrelvir, which inhibits a key enzyme that the COVID virus requires in order to make functional virus particles. After nirmatrelvir treatment, the COVID virus that is released from the cells is no longer able to enter uninfected cells in the body, which, in turn, stops the infection. The other is ritonavir, a drug that was once used to treat HIV/AIDS but is now used to boost levels of antiviral medicines.
As a COVID-19 treatment, ritonavir essentially shuts down nirmatrelvir’s metabolism in the liver, so that it doesn’t move out of your body as quickly, which means it can work longer—giving it a boost to help fight the infection.
2. When should I take Paxlovid?
You have to take Paxlovid within five days of developing symptoms.
Like all antivirals, Paxlovid works best early in the course of an illness—in this case, within the first five days of symptom onset, says Jeffrey Topal, MD, a Yale Medicine infectious diseases specialist who is involved in determining COVID-19 treatment protocols for Yale New Haven Hospital patients.
“Once you’ve been ill with the virus for more than a week, the damage done to the body in a severe case can’t be undone by the antiviral,” he says.
3. How often do I take Paxlovid?
The standard dose is three Paxlovid pills twice daily for five days for a full course that adds up to 30 pills. It helps that the pills are packaged in a “dose card,” basically a medication blister pack that allows you to punch out the pills as needed. There is also a reduced dose (two pills instead of three) for people with moderate renal impairment.
4. Is Paxlovid similar to Tamiflu?
“I think it's a good comparison,” says Dr. Roberts. Tamiflu is an antiviral drug that reduces flu symptoms. Both are prescription-only oral antiviral pills given early in illness.
Tamiflu is taken twice a day for five days, and it must be started within 48 hours of flu onset. “When you give a patient Tamiflu beyond that, it doesn’t really change the course of their flu,” Dr. Roberts says.
But there are also differences between the two, starting with the way they were studied, Dr. Topal adds. Researchers showed that Paxlovid can prevent hospitalization and death. But since influenza causes fewer severe cases, clinical trials focused on whether Tamiflu could shorten the length of flu illness—which it did, he says.
5. Can anyone get a Paxlovid prescription?
In order to qualify for a prescription, you must be at high risk for developing severe COVID-19. That means you must either be 50 or older (age remains the strongest factor for severe COVID-19 outcomes, according to the FDA), although, the agency still authorizes Paxlovid for adolescents and teenagers ages 12 and older who weigh at least 88 pounds. You also qualify if you have certain underlying conditions (including cancer, diabetes, obesity, or others). The more underlying medical conditions a person has, the higher their risk for developing a severe case of COVID-19, according to the CDC.
Determining whether a patient is at high risk for progression to severe COVID-19, including hospitalization or death, is based on the provider’s assessment of the individual patient and that patient’s medical history, according to the FDA. If you are pregnant or breastfeeding, the FDA recommends discussing your options and specific situation with your health care provider, since there is no experience using the drug in these populations. If you could become pregnant, it’s recommended that you use effective barrier contraception or do not have sexual activity while taking Paxlovid.
It’s important to note that although health care providers can write a prescription, pharmacists may also provide Paxlovid (with certain limitations) if they’ve opted to do so, provided you can share your electronic or printed medical records, including a list of medications you are already taking, and blood test results from the last 12 months.
6. How well does Paxlovid work?
The FDA’s approval of Paxlovid for adults in 2023 was based on the totality of scientific evidence submitted by Pfizer, including efficacy data from a Phase 2/3 study showing an 86% reduction in risk of COVID-19-related hospitalization or death from any cause in patients who took Paxlovid within five days of symptom onset.
When it applied for FDA authorization in 2021, Pfizer presented data from a clinical trial conducted between mid-July and early December 2021. That data showed that participants, who were given Paxlovid were 89% less likely to develop severe illness and death compared to trial participants who received a placebo. All of the trial participants were unvaccinated and they took the drug within three days of symptom onset.
In November 2022, the CDC reported on a real-world study that showed adults who took Paxlovid within five days of a COVID-19 diagnosis had a 51% lower hospitalization rate within the next 30 days than those who were not given the drug. The study included people who had been vaccinated or had a previous infection, which the CDC said implied the drug should be offered to people who are eligible regardless of their vaccination status.
7. What do we know about how Paxlovid works in kids?
Pfizer launched a clinical trial in March 2022 to study the safety and efficacy of Paxlovid in children and teenagers ages 6 to 17 who have COVID-19 symptoms and test positive for the virus, and who are neither hospitalized nor at risk for severe disease.
While Paxlovid is authorized for use in adolescents and teenagers ages 12 and up, and weighing at least 88 pounds, that age group wasn’t tested in the original clinical trial. But because many children reach 88 pounds—considered to be an adult weight—the FDA has allowed extensions of EUAs for medications such as monoclonal antibodies and remdesivir in younger age groups, adds Dr. Topal.
“Based on the pharmacokinetics of the drugs in Paxlovid, the differences in metabolism and excretion—liver and kidney function specifically—of these drugs in this age group are thought to be similar to that of adults,” Dr. Topal says.
8. Does Paxlovid work against Omicron subvariants EG.5 and BA.2.86?
Dr. Roberts says Paxlovid should work against the Omicron subvariant EG.5, which is currently the dominant strain in the U.S., and which has similarities to previous Omicron strains. The CDC reported that while it continues to monitor the situation, it expects Paxlovid to be effective against the new Omicron subvariant BA.2.86, which scientists are still learning about.
9. What are the side effects from Paxlovid?
The most common side effects of taking Paxlovid include impaired sense of taste (for example, a metallic taste in the mouth) and diarrhea, according to the FDA. Most people who take Paxlovid should not experience serious side effects, explains Dr. Roberts. “Paxlovid is usually very well-tolerated,” he says.
But people should stop taking Paxlovid and call a health care provider right away if they experience any of the following signs of an allergic reaction:
- hives
- trouble swallowing or breathing
- swelling of the mouth, lips, or face
- throat tightness
- hoarseness
- skin rash
Other possible side effects include:
- an altered or impaired sense of taste
- diarrhea
- increased blood pressure
- muscle aches
- abdominal pain
- nausea
- feeling generally unwell
Since Paxlovid is cleared by the kidneys, dose adjustments may be required for patients with mild-to-moderate kidney disease, explains Dr. Topal. “For patients with severe kidney disease—or who are on dialysis—or those with severe liver disease, Paxlovid is not recommended; the levels of the drug can become too high and could cause increased side effects,” he says.
The FDA says that anyone who takes Paxlovid should contact their health provider right away if they have any signs and symptoms of liver problems: loss of appetite, yellowing of the skin and whites of the eyes (jaundice), dark-colored urine, pale-colored stools and itchy skin, or stomach-area (abdominal) pain.
It’s worth noting that because Paxlovid is still being monitored in the real world, it is possible that all of the risks are not yet known. (The FDA has provided a fact sheet on Paxlovid with a full list of known side effects.)
10. Can I take Paxlovid if I'm taking other medications?
There is a long list of medications Paxlovid may interact with, and in some cases, doctors may not prescribe Paxlovid because these interactions may cause serious complications.
The list of drugs that Paxlovid interacts with includes some organ anti-rejection drugs that transplant patients take, as well as more common drugs like some used to treat heart arrhythmias. Paxlovid also decreases the metabolism of anticoagulants, or blood thinners, that many older adults depend on, driving up levels of those medications in the body to a point where they are unsafe, Dr. Topal explains.
Anyone who has Human Immunodeficiency Virus 1 (HIV-1) infection should talk to their health care provider before taking Paxlovid, since it may lead to some HIV-1 medicines not working as well in the future.
Paxlovid also interacts with common medications, including cholesterol-lowering statins like Lipitor. But in many cases, patients can talk to their doctors about taking a temporary break from some of those drugs while taking Paxlovid, he adds. “As always, patients should speak with their providers when starting new medications and follow their providers’ directions regarding the stopping or holding of any medications,” Dr. Topal says.
11. What is the rebound effect of Paxlovid?
There have been reports of a “rebound” of COVID-19 symptoms in some people within 2 to 8 days after completing the five-day course of Paxlovid; in those cases, some have tested positive again but have no symptoms; others have a recurrence of symptoms. Pfizer had said that in the clinical trial for Paxlovid, several participants appeared to have a rebound in virus levels, although this also occurred in some people who were given a placebo.
When it approved Paxlovid in May, the FDA said there not a clear association between Paxlovid treatment and COVID-19 rebound based on available data, and rebound rates in clinical trials were similar among participants who took Paxlovid and those who took a placebo.
However, scientists are still studying the Paxlovid rebound. The CDC says a rebound does not mean a person was resistant to Paxlovid, nor does it mean they were reinfected with the virus. In June, the CDC released guidance for clinicians, saying a brief return of symptoms may be part of the natural history of SARS-CoV-2 infection in some people, independent of treatment with Paxlovid, adding that there is no evidence additional treatment is needed. A CDC studyreported that rebound symptoms tended to be unlikely to require hospitalization and milder than symptoms experienced during the primary infection.
“The hypothesis is that the immune system didn’t have a chance to see the full extent of the virus, since Paxlovid suppressed replication early in disease,” Dr. Roberts says. Scientists are studying the effects of longer treatment durations, longer periods of isolation, and other ways of managing the problem, he adds.
For anyone who experiences a rebound, Pfizer recommends reporting it to them on its portal for adverse events associated with Paxlovid.
12. If I'm not eligible for Paxlovid, is there something else I can take?
There are other therapies for COVID-19, and anyone who cannot take Paxlovid—perhaps because it would interact with another medication—should talk to their doctor about the best approach for their situation.
13. Do I still need to be 'up to date' on vaccination if Paxlovid is available?
Vaccination, testing, and mitigation efforts such as masking, remain a key part of prevention, even as more drugs become available, says Dr. Topal.
“Early testing is key to making these drugs work,” he says. “It’s always been the Achilles’ heel of these antiviral drugs that most people don’t get tested—or they don’t have access to testing.”
He encourages taking a test even if you think you only have a cold or allergies—and if you can get one. “Home testing is a huge part of the way to really ‘operationalize’ these medications,” he says, adding that while home tests may not be as highly sensitive as the laboratory-based polymerase chain reaction (PCR) tests, they are still very helpful in making a diagnosis.
Dr. Topal says people also should remember that Paxlovid, even with its high efficacy, is not perfect, and even if it were, viruses can mutate and develop resistance to antiviral medications. “Will some people still be hospitalized? Yes—no medication is perfect,” he says. “But for many high-risk patients, this medication can really reduce that risk.”
If you are experiencing symptoms of COVID-19and think you are eligible for a treatment, you can visit the government Test-to-Treat Locater. You can use the site to search for the places near you where you can fill a COVID-19 prescription, or identify sites that provide testing, medical care, and COVID-19 medications.
For answers to more Paxlovid-related questions, read the Paxlovid FAQ provided by the FDA.
Information provided in Yale Medicine articles is for general informational purposes only. No content in the articles should ever be used as a substitute for medical advice from your doctor or other qualified clinician. Always seek the individual advice of your health care provider with any questions you have regarding a medical condition.
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