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What to know about Paxlovid: Side effects, drug interactions, and rebound infections

June 17, 2022, 7:35 PM UTC
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Fabian Sommer—picture alliance/Getty Images

In December, the Food and Drug Administration authorized emergency use of Pfizer’s antiviral pill Paxlovid for people at high risk of developing severe COVID-19. The drug was 89% effective in reducing the risk of hospitalization and death when taken within three days of the onset of symptoms, and 88% effective for reducing hospitalization and death when taken within five days, according to a study performed by Pfizer

“This is kind of helping us transition from an epidemic phase into an endemic phase for COVID,” says Dr. Andrew Jameson, section chief of infectious diseases at Trinity Health Saint Mary’s Hospital. “These oral antivirals are really important tools to help us get to the point where we can live with COVID without it hurting as many people. That’s the whole goal right now.” 

This week, Pfizer halted a trial looking into the drug’s efficacy for those with a “standard risk” for developing severe COVID, citing a “non-significant” reduction in hospitalization and death for this group. Still, medical professionals tout Paxlovid’s impact for those in high-risk groups.

How does Paxlovid work?

Paxlovid is an antiviral therapy and a combination of two drugs (nirmatrelvir and ritonavir) that help prevent replication of the virus’s protein particles responsible for the spread of COVID in the body. 

Who should take Paxlovid?

Paxlovid is for people age 12 and older, with mild to moderate cases of COVID-19, who are at high risk for developing severe COVID. High-risk groups include those with certain underlying conditions, like diabetes, people who’ve had an organ transplant or who are over 65. The list of high-risk conditions is long and nuanced, so it’s best to talk to your doctor to determine whether you’re in this group.

When should I take Paxlovid? 

For Paxlovid to be effective, it needs to be taken within five days of developing symptoms. 

How do I get Paxlovid? 

“The message that I really would like to get out is, have a plan,” said Dr. Preeti Malani, professor of medicine in the division of infectious diseases at the University of Michigan. 

Malani says to contact a primary care doctor to prescribe the medication as soon as you test positive. An at-home rapid test is sufficient to get the prescription, so you don’t have to scramble to find further testing while contagious. Additionally, you can go to urgent care (some pharmacies have urgent care), where you can make an appointment online, take a test, meet with a provider, and get a prescription for the antiviral pill. 

What are the side effects of Paxlovid? 

The most common side effects include nausea, upset stomach, diarrhea, impaired taste, and muscle aches. 

Tell your doctor or health care professional about conditions you have or other drugs you’re taking. Those with severe kidney or liver disease should not take the medication, says Dr. Scott Roberts, associate medical director of infection prevention at Yale New Haven Hospital. Some medications, like those used for heart arrhythmias and to lower cholesterol, for example, can have an unsafe interaction.

“That doesn’t mean you can’t take it. It might mean it’ll be recommended that you hold a medication like a cholesterol pill, for example, but it’s really important that whoever’s prescribing medications to you knows what drugs you’re taking,” Malani says.

What is Paxlovid rebound? 

Recently, there have been reports about a “rebound effect” for those taking Paxlovid, a phenomenon where people’s symptoms improve, only to return two to eight days after their initial recovery.

Jameson suspects that because patients take the oral medication early in the disease’s progression, their immune system has not gone through its entire process of mitigating the virus. 

“Your immune system hasn’t really had a chance to catch up and really create enough antibodies to have a sustained response,” Jameson says. 

A study released this week from the Mayo Clinic found that out of the 483 qualified patients treated with Paxlvoid, only four reported rebound symptoms. 

“There’s no data to suggest that these people need extra treatment courses…but it’s a new finding, so there’s a lot of investigation going into this right now,” Roberts says.

Medical experts say further research is needed to understand the nuances in these cases but note that hospitalization remains reduced, and those at high risk for developing severe COVID-19 cases should still consider taking the drug. 

“At the start of this pandemic, I never would have imagined something so successful as a therapeutic that is oral that can be taken at home,” says Roberts. “I think this is really remarkable.”

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