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Side Effects
cartoon shows a woman sitting a table with pill bottles and syringes. She is holding many pills in her hand and has an inquisitive expression

Pfizer’s Paxlovid is an antiviral pill for COVID-19 currently authorized for use in those high-risk for severe outcomes, which makes it a particularly important tool in the immunocompromised patient’s arsenal against the virus. However, if your doctor prescribes you Paxlovid, a slew of questions may come to mind: How does Paxlovid work? What side effects should I expect? What happens if I miss a dose?

Bookmark this guide so you can have it handy if you’re prescribed the drug — and read on for what experts want you to know as an immunocompromised individual. 

Who Is Eligible for Paxlovid?

Paxlovid is meant to treat mild to moderate COVID-19 in adults and pediatric patients (age 12 and up) who have tested positive and are at high risk for progression to severe COVID-19, including hospitalization or death, per the U.S. Food & Drug Administration

It is not authorized for patients who are already hospitalized, as a preventive measure before or after exposure to COVID-19, or for use longer than five days. 

Although this is not required for a prescriber to write a script for Paxlovid under the Emergency Use Authorization, the FDA compiled an eligibility screening checklist for prescribers to use a tool when deciding if a patient should receive Paxlovid: 

  • A positive SARS-coV-2 test
  • Age over 18 years or over 12 years and weighing at least 40 kilograms (about 88 pounds) 
  • Has one or more risk factors for progression to severe COVID-19, such as having an immunocompromised condition or weakened immune system
  • Symptoms consistent with mild to moderate COVID-19 
  • Symptom onset within five days
  • Not requiring hospitalization due to severe or critical COVID-19 at treatment initiation
  • No known or suspected severe renal impairment 
  • No known or suspected severe hepatic impairment
  • No history of clinically significant hypersensitivity reactions to the active ingredients or other components of the product

Paxlovid is an important drug for immunocompromised patients to know about because they may have a higher risk of severe COVID-19 — which is something a doctor would consider when prescribing the drug. 

“One of the advantages of Paxlovid is that it’s pretty easy to take, and another advantage is that it works independently of the person’s immune system — in other words, it directly targets the virus,” says David Aronoff, MD, Chair of the Department of Medicine at Indiana University School of Medicine.

This can make it a helpful treatment tool for those who are immunocompromised and may not have garnered a full immune response to the vaccine. 

How Does Paxlovid Work Against COVID-19?

Each three-pill dose of Paxlovid includes two different medications packaged together: nirmatrelvir (two pills) and ritonavir (one pill). 

Nirmatrelvir inhibits the SARS-Cov-2 protein from replicating. Meanwhile, ritonavir (once used to treat HIV/AIDS) is used to boost levels on antiviral medicines and thwarts nirmatrelvir’s metabolism in the liver, per Yale Medicine. This helps nirmatrelvir stay in your body for longer and extends the amount of time it works for, giving it extra power in fighting the infection. 

You’ll receive 30 total pills — expect to take three pills twice daily for five days. You’ll receive them in a blister pack labeled with daytime and nighttime doses, so you can keep track of the medication. 

“It’s a very potent antiviral drug and will help stop the ability of the virus to reproduce itself in a patient’s body, whether they’re immunocompromised or not,” says Dr. Aronoff. “It’s really viral replication that is part of what causes damage to the infected person’s body, so when you can stop the virus from multiplying, you can limit the amount of damage the virus can do — which in turn, limits the symptoms that result from that damage.”

Like other antivirals, Paxlovid needs to be taken early in the course of the illness (within the first five days of symptom onset). That’s because damage caused by the virus in the body after a week can’t be reversed by the antiviral pill — and even within the first five days, it’s likely that taking the drug sooner is better. 

“The longer someone is symptomatic and infected, the more opportunity there is for the virus to cause harm and to start the process that leads someone into a more severe category of COVID,” says Dr. Aronoff. “The earlier we can get in the way of that process, the earlier we can prevent viral replication and damage, and the better our chances to keep someone from having severe disease.”

With COVID-19, the early part of the disease is characterized by massive viral multiplication, which causes damage. The later part of the disease is driven by the inflammation from your own immune system as it tries to respond to the infection. Inflammation and immune response, in an attempt to heal the damage caused by the virus, often lead to severe pneumonia or difficulty with kidney function. 

“The goal, therefore, is to get in early to block viral replication before the horse has the chance to leave the barn,” says Dr. Aronoff. “So yes, there can be benefits of Paxlovid on day four or day five, but the mantra with these drugs targeting the virus is the earlier, the better.” Paxlovid should start working very quickly, though it may take a few doses for the drug to reach its key concentration in the body.

If you miss a dose of Paxlovid within eight hours of the time it’s normally taken, you should take that dose as soon as possible and return to your normal dosing schedule, per the FDA. If you miss a dose by more than eight hours, skip that dose and resume the next dose at the normal time (in this case, you shouldn’t double up on doses to make up for the missed dose). 

You can take Paxlovid with or without food. 

What Are the Side Effects of Paxlovid?

Side effects of Paxlovid are usually mild and include altered taste, diarrhea, high blood pressure, and body aches.

“Side effects might include gastrointestinal upset or diarrhea due to the ritonavir component,” says Jeffrey D. Klausner, MD, MPH, Clinical Professor of Medicine, Population, and Public Health Sciences in the Keck School of Medicine of the University of Southern California

Meanwhile, the altered taste experienced with Paxlovid has been dubbed “Paxlovid mouth.” Patients have reported a metallic, bitter, or grapefruit taste in the mouth that lingers. “I imagine this is what grapefruit juice mixed with soap would taste like,” Anna Valdez, a nursing professor in Sonoma Valley, California, told The Atlantic.

As you may already know from your existing medications, altered taste is sometimes an unavoidable part of certain drugs.

“It’s not uncommon for medications to cause changes in taste — we see that quite a lot with various antibiotics that we use,” says Dr. Aronoff. “With changes in taste, sometimes mouthwashes that are highly flavored or lozenges that are flavored or gum may help.”

Taking Paxlovid with certain medications can cause serious or life-threatening side effects or change how it works (see “Who Should Not Take Paxlovid?”). 

How Well Does Paxlovid Work?

In a clinical trial, Paxlovid was found to reduce the risk of hospitalization or death by 89 percent compared to placebo in non-hospitalized high-risk adults with COVID-19, per Pfizer. One percent of patients who received Paxlovid were hospitalized through day 28 following randomization compared to 6.7 percent of patients who received a placebo. In the overall study population through day 28, no deaths were reported in patients who received Paxlovid, compared to 10 deaths in patients who received placebo. 

You may see your symptoms begin to improve as soon as one day after your first dose. “It has been reported that symptoms can improve within 24 to 48 hours,” says Julie Paik, MD, Director of Clinical Trials at the Johns Hopkins Myositis Center. 

Who Should Not Take Paxlovid?

Since the kidneys clear Paxlovid, patients with mild-to-moderate kidney disease may require dose adjustments (Paxlovid is not recommended at all for those with severe kidney disease — or who are on dialysis — or those with severe liver disease), per Yale Medicine. And of course, those who have had allergic reactions to the active ingredients in Paxlovid should not take it. 

You also shouldn’t take Paxlovid if you’re on certain types of medications. It’s important to be upfront with any prescriber about the medications you’re taking, since many may interact with Paxlovid and lead to serious complications.

According to the FDA, Paxlovid should not be taken with the following types of drugs: 

  • ​​Alpha1-adrenoreceptor antagonist: alfuzosin 
  • Analgesics: pethidine, propoxyphene 
  • Antianginal: ranolazine 
  • Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine 
  • Anti-gout: colchicine 
  • Antipsychotics: lurasidone, pimozide, clozapine 
  • Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine  
  • HMG-CoA reductase inhibitors: lovastatin, simvastatin 
  • PDE5 inhibitor: sildenafil (Revatio®) when used for pulmonary arterial hypertension (PAH)
  • Sedative/hypnotics: triazolam, oral midazolam
  • Anticancer drugs: apalutamide 
  • Anticonvulsant: carbamazepine, phenobarbital, phenytoin 
  • Antimycobacterials: rifampin 
  • Herbal products: St. John’s Wort (hypericum perforatum) 

Paxlovid can interact with several other types of drugs, including organ anti-rejection drugs, medications used to treat heart arrhythmias, and systemic corticosteroids like betamethasone, dexamethasone, and prednisone (these corticosteroid interactions increase the risk for Cushing’s syndrome, a disorder involving the hormone cortisol, and adrenal suppression). 

There is also a strong interaction with tacrolimus, an immunosuppressant commonly used by patients with autoimmune diseases or those who have had transplants,” says Dr. Paik.

For a full list of potential drug interactions, see the fact sheet from the FDA.

“You should make sure that if you’re on other medications, the person prescribing Paxlovid knows that you are on those, and have a conversation with the pharmacist who fills your medications to make sure there are not any important drug interactions,” says Dr. Aronoff.

What’s Next for Paxlovid?

“Rebound” COVID-19 symptoms have been reported in some patients who completed the five-day course of Paxlovid. This means that symptoms recurred four or five days after completing the treatment or the patient had a positive COVID-19 test even after completing the drug, per Yale Medicine. 

In the clinical trial for Paxlovid, several participants appeared to have a virus level rebound around day 10 or day 14 (though this also was seen in some given the placebo).

Experts are now studying the effects of longer treatment durations for Paxlovid. If you do experience a rebound, you can report it to Pfizer on their portal for adverse events associated with Paxlovid

In the future, Paxlovid may be used to treat those who are not high risk for COVID-19 as well — and some doctors have already prescribed it in this way. “While those non-immunocompromised or not at high-risk are unlikely to get hospitalized, Paxlovid can quickly reduce symptoms in everyone and might reduce their risk for long COVID,” says Dr. Klausner. “The impact of Paxlovid on long COVID is under study.” 

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Fact Sheet for Healthcare Providers: Emergency Use Authorization for Paxlovid. U.S. Food & Drug Administration. April 14, 2022. https://www.fda.gov/media/155050/download.  

Interview with David Aronoff, MD, Chair of the Department of Medicine at Indiana University School of Medicine

Interview with Jeffrey D. Klausner, MD, MPH, Clinical Professor of Medicine, Population, and Public Health Sciences in the Keck School of Medicine of the University of Southern California

Interview with Julie Paik, MD, Director of Clinical Trials at the Johns Hopkins Myositis Center

Paxlovid Mouth Is Real — And Gross. The Atlantic. May 5, 2022. https://www.theatlantic.com/health/archive/2022/05/pfizer-paxlovid-covid-pill-side-effects/629772/

PAXLOVID Patient Eligibility Screening Checklist Tool for Prescribers. U.S. Food & Drug Administration. May 22, 2022. https://www.fda.gov/media/158165/download

Pfizer’s Novel COVID-19 Oral Antiviral Treatment Candidate Reduced Risk of Hospitalization or Death by 89% in Interim Analysis of Phase 2/3 EPIC-HR Study. Pfizer. November 5, 2021. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate

13 Things To Know About Paxlovid, the Latest COVID-19 Pill. Yale Medicine. May 12, 2022. https://www.yalemedicine.org/news/13-things-to-know-paxlovid-covid-19

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