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Paxlovid side effects and how to avoid them

Paxlovid side effects include COVID-19 rebound and a bad taste in the mouth. Interactions with other drugs could cause serious or life-threatening problems.
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By | Dec. 1, 2023 Medically reviewed by Josephine Bawab, Pharm.D.
A bottle of pills spilled over: Paxlovid side effects

Key takeaways

  • Paxlovid is an FDA-authorized antiviral medication for treating mild-to-moderate COVID-19, designed to reduce viral load by preventing virus reproduction and maintaining effective drug levels in the bloodstream.

  • Common side effects of Paxlovid include taste disturbances, diarrhea, and less frequently, severe allergic reactions, liver problems, and COVID-19 symptom rebound.

  • Paxlovid interacts significantly with many other medications, potentially causing serious or life-threatening issues, necessitating careful management of drug combinations.

  • While most side effects of Paxlovid are mild and resolve after treatment, the medication requires careful prescription and adherence to safety measures, especially regarding dosing and potential drug interactions.

In this article:

Paxlovid (nirmatrelvir-ritonavir) is a prescription medication that has been given an Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) to treat COVID-19. Paxlovid is an antiviral two-drug treatment that works by reducing the viral load in the body. The first drug in the treatment, nirmatrelvir, prevents the SARS-COV-2 virus from reproducing. The second drug, ritonavir, is a protease inhibitor that prevents the liver from breaking down nirmatrelvir. This keeps nirmatrelvir at high enough levels in the bloodstream to effectively suppress the coronavirus infection. People prescribed Paxlovid will take two 150 mg nirmatrelvir tablets and one 100 mg ritonavir tablet twice per day for five days. Side effects are relatively minimal, but there are serious drug interactions that can cause severe and life-threatening problems.

Common side effects of Paxlovid

In clinical trials, the most common side effects reported were taste disturbances or bad taste (about a 6% incidence) and diarrhea (about 1%). The complete list of side effects includes:

  • Alterations to the sense of taste (bad taste or metallic taste)
  • Diarrhea
  • Headache
  • Abdominal pain
  • Nausea
  • Vomiting
  • Feeling sick (malaise)
  • Muscle aches
  • High blood pressure (hypertension)

Serious side effects of Paxlovid

Possible serious side effects of Paxlovid include:

  • Severe allergic reactions, including anaphylaxis
  • Severe skin reactions
  • Liver problems

Paxlovid and COVID-19 rebound

Some people who have been treated with Paxlovid experience a relapse of COVID-19 symptoms, a phenomenon called Paxlovid rebound. According to the Centers for Disease Control and Prevention, some cases of Paxlovid rebound involve a return of symptoms without testing positive, and some cases involve a return of symptoms with a positive COVID-19 test. Pfizer’s clinical trials determined that 1% to 2% of people treated with Paxlovid had COVID-19 rebound. The median time from the end of Paxlovid treatment to rebound symptoms was nine days. 

Paxlovid and kidney problems

Paxlovid FDA-prescribing information states that a lower dose may be needed if kidney disease is present. Paxlovid isn’t recommended for people with serious kidney disease or those who are on dialysis. 

Paxlovid and bad taste in the mouth (Paxlovid mouth)

A foul taste in the mouth is the most commonly reported adverse effect of Paxlovid. Although clinical trials found that 5% to 6% of trial participants complained of taste disturbance (dysgeusia), a subsequent study found the incidence to be over 17%. Whatever the incidence is, it’s common enough that it’s been given a name: Paxlovid mouth. Some people report taste disturbance within an hour of taking the first dose. More research is needed to identify the cause, but the bad taste will go away when treatment is discontinued.

How soon do Paxlovid side effects start?

People may notice taste changes within hours of taking the first dose of Paxlovid. Other side effects are minor and could occur at any time during the five-day treatment regimen.

How long do Paxlovid side effects last?

Most Paxlovid side effects will pass when the five-day treatment period ends. Liver problems or allergic reactions may take several days or weeks to resolve.

What are the long-term side effects of Paxlovid?

As of this date, there are no long-term side effects associated with Paxlovid. However, Paxlovid has only recently gone through clinical trials and is currently FDA-approved because the COVID-19 pandemic is considered a public health emergency. Healthcare providers may discover other adverse effects in the future, including long-term side effects. 

Paxlovid interactions

Paxlovid has a boxed warning that highlights significant drug-drug interactions. 

The liver has several enzymes and mechanisms for breaking down drugs. The ritonavir component of Paxlovid interferes with several of them. As a result, drugs broken down through these mechanisms will build up in the body, significantly raising the risk for adverse effects. For this reason, Paxlovid cannot be taken with any medication that would cause serious or life-threatening problems due to high drug concentrations caused by an interaction. These include:

Paxlovid should not be taken with any drugs that speed up the mechanisms that break down nirmatrelvir, as those drugs will significantly reduce Paxlovid’s ability to fight the virus that causes COVID-19. These drugs include:

The FDA also warns that Paxlovid interferes with the effectiveness of hormonal birth control, so women are urged to use alternative contraception when taking Paxlovid.

Safety measures while using Paxlovid

Because of its emergency authorization, Paxlovid is only prescribed to adults and children 12 years and older with mild-to-moderate COVID-19 who are at high risk of developing severe COVID-19, including hospitalization or death. The safety of Paxlovid is fairly well-established, but more safety data may become available as more people take the drug.

Precautions

Paxlovid cannot be used by anyone who has had a severe hypersensitivity reaction to nirmatrelvir or ritonavir. 

Several medical conditions may require dosage restrictions. People with moderate kidney disease may need to take a reduced dose. People with severe kidney disease may not be able to take the drug at all. Those with liver disorders can take the drug if liver dysfunction is mild or moderate, but Paxlovid should be avoided in people with severe liver dysfunction. 

Ritonavir is used to treat HIV, the virus that causes AIDS. Giving Paxlovid to someone with both COVID-19 and HIV can increase the risk of developing resistance to the protease inhibitor drug class to treat HIV. Therefore, it is very important that anyone with HIV speaks to their infectious disease specialist before taking Paxlovid.

Children

Paxlovid has FDA approval for use in children as young as 12 years old who weigh at least 88 pounds. As with adults, children are only prescribed Paxlovid if they have a high risk of developing severe COVID-19.

Pregnancy

Because Paxlovid is an emergency-approved drug that is still early in its formal approval process, there is limited information on the safety of taking it while pregnant. However, prior studies of its individual components, nirmatrelvir and ritonavir, show that it is considered safe to take during pregnancy.

Breastfeeding

There is a lack of research on the effects of Paxlovid on lactation and nursing. Women who are breastfeeding should ask for medical advice about the risks and benefits of taking Paxlovid. 

Dependence

Paxlovid does not cause dependency. There are no known withdrawal symptoms when the drug is discontinued.

Overdose

There is a lack of information about the consequences or symptoms of a Paxlovid overdose. If too much Paxlovid is taken, call the prescribing healthcare provider or get emergency medical care. 

Recalls

Paxlovid has not been recalled for any reason. 

How to avoid Paxlovid side effects

As a prescription medication, Paxlovid can be risky to take. The risks of side effects can be reduced by following some fundamental rules:

1. Tell the prescriber about all medical conditions

The prescribing healthcare provider needs to know about all past and present medical conditions—particularly kidney problems, liver problems, hepatitis, or an HIV infection.

2. Tell the prescriber and pharmacist about all drugs and supplements you’re taking

The riskiest aspect of taking Paxlovid involves drug interactions. Give your prescriber or pharmacist a complete list of all prescription drugs, over-the-counter medications, and dietary supplements you’re taking. A healthcare professional can tell you which of those drugs are unsafe to take with Paxlovid.

3. Take Paxlovid as instructed

Paxlovid is a complicated medicine to take, requiring three pills to be taken for each dose in order for it to be effective. Never take an extra dose or tablet to make up for a missed dose. 

How to treat side effects of Paxlovid

Most Paxlovid side effects are minimal. A few can be more problematic. Here’s how to handle some of the most unpleasant or serious side effects of Paxlovid:

  • Bad taste: Getting a persistent, bad taste in the mouth is among the least pleasant side effects a drug can have. Fortunately, an unpleasant taste in the mouth is not a health threat unless someone stops eating or drinking. Although there’s little to do about it, a few things may help. Don’t eat foods with a bitter taste. Don’t put metal in your mouth; use plastic utensils instead. Brushing your teeth or eating candies may also help.
  • Liver problems: Paxlovid can injure the liver. If you notice symptoms of liver dysfunction, such as pale stools, jaundice (yellowing of the eyes or skin), dark-colored urine, upper abdominal pain, itchy skin, or loss of appetite, immediately contact a healthcare provider. You may need to stop taking the drug.
  • COVID-19 rebound: If COVID-19 symptoms return in the days or weeks following Paxlovid treatment, begin isolation at home just as you would with a new infection. Many people with Paxlovid rebound get over their symptoms quickly. In that case, isolation can end five days after the fever recedes. People with Paxlovid rebound do not need further treatment with the drug.
  • Hypersensitivity reactions: Immediately stop taking Paxlovid and get immediate medical help if you notice symptoms of hypersensitivity, such as a skin rash, hives, blisters, peeling skin, trouble breathing, facial swelling, difficulty swallowing, or tightness in the throat. These are all signs of a potentially severe allergic reaction or drug reaction.

Bottom line: Is Paxlovid safe?

At this time, Paxlovid is only used in people infected with mild-to-moderate COVID-19 who are at risk of developing severe and potentially life-threatening COVID-19. That means the risks of Paxlovid must be weighed against the risk of hospitalization or death. Paxlovid has relatively few possible side effects. Most side effects are mild and not commonly experienced. The most significant warnings about taking Paxlovid are in regard to its potentially severe or fatal drug interactions.