Pfizer’s COVID-19 pill has some serious medication interactions

A young woman takes a pill with a glass of water from her bed.

Paxlovid® is one of the most effective treatments available to prevent severe COVID-19. But the FDA-authorized antiviral may be risky if you take certain long-term medications.

Pfizer’s Paxlovid (nirmatrelvir and ritonavir tablets) is an oral antiviral regimen for the treatment of mild-to-moderate COVID-19. The oral medication is intended for patients 12 years and older who have tested positive for COVID-19 and are at high risk for developing severe disease — either due to age or underlying health conditions, such as diabetes, heart disease, cancer, chronic lung disease, or a weakened immune system.

Paxlovid can be taken in the comfort of your own home. No hospital, no doctor’s office, no IV.

While the clinical study that led to Paxlovid‘s Emergency Use Authorization (EUA) shows it to be highly effective at preventing hospitalization and death if started early enough, the treatment poses a number of serious risks if you take other long-term medications.

We spoke with two Express Scripts® Pharmacy registered pharmacists, Robert Sardon and Marie Jacinto-Dearing, about how Paxlovid works, which medications interact with Paxlovid, and how your care team can work together to decide if Paxlovid is right for you.

How does Paxlovid work?

SARS-CoV-2, the virus that causes COVID-19, requires an enzyme called a protease to be able to multiply within our bodies. Paxlovid works by binding to the protease enzyme and prevents the virus from making more copies of itself. This cuts down the amount of time a patient is sick and helps to limit the damage caused by the virus.

How is Paxlovid taken?

Paxlovid comes in two doses. The standard dose is a combination of two 150mg tablets of the antiviral nirmatrelvir and one 100mg tablet of the antiviral ritonavir. Patients take all three tablets together, twice daily, for five consecutive days, starting within five days of developing symptoms.

If you have kidney disease or any condition that affects kidney function, your doctor or pharmacist may prescribe a lower-dose pack of Paxlovid consisting of only one 150mg tablet of nirmatrelvir and one 100mg tablet of ritonavir.

It’s important to note that Paxlovid is not used to prevent COVID-19 and isn’t authorized for patients who are already hospitalized with severe COVID-19 or for use for more than five consecutive days.

What are the side effects of Paxlovid?

As with any medication, there may be side effects that occur when taking Paxlovid. The most common reported side effects are altered sense of taste, diarrhea, high blood pressure, and sore or achy muscles. Patients should reach out to their doctor or pharmacist immediately if they experience loss of appetite, yellowing of skin or eyes, itchy skin, or dark-colored urine as these may indicate liver problems.

There have been reports of some people relapsing — developing COVID-19 symptoms again and testing positive for COVID-19 days after finishing their full 5-day treatment of Paxlovid. (This is often referred to as “COVID rebound.”) If you relapse, the FDA does not recommend repeating a treatment course of Paxlovid or taking Paxlovid for a longer period of time. Instead, reach out to your doctor to find out how best to treat your symptoms and continue to follow health guidelines.

Who should not take Paxlovid?

Patients should let their doctor or healthcare provider know if they have kidney or liver disease or any other serious illness. The dose of the medication may need to be adjusted or, in some cases, it may not be recommended. Paxlovid has not been studied in those who are pregnant or breastfeeding. These patients should discuss alternative options with their healthcare provider or pharmacist.

How does Paxlovid interact with other medications?

“The reason there are many medication interactions with Paxlovid is because of the ritonavir,” explains Sardon. “The body metabolizes nirmatrelvir, the antiviral, so quickly that the medication wouldn’t be able to do its job without ritonavir.”

Ritonavir works by suppressing a key liver enzyme that breaks down the nirmatrelvir. This makes it so the nirmatrelvir can remain in the body long enough to effectively stop the virus from replicating. However, Paxlovid’s ritonavir also keeps your liver from metabolizing other drugs, Sardon warns — hence all the interactions.

What medications interact with Paxlovid?

Paxlovid has the potential to interact with more than 20 different classes of prescription medications. Some of the more common ones are cholesterol medications known as statins, antiplatelet medications given after a heart attack or stent placement, cardiac medications that treat abnormal heart rhythms, medications that treat seizure disorders, birth-control medications, and opioid pain relievers.

Even some over-the-counter herbal supplements, such as St. John’s Wort, should be avoided while taking Paxlovid.

“Vitamins and minerals can impact other medications,” says Jacinto-Dearing. “Our pharmacists see this come up a lot where patients forget to mention everything they’re taking, including over-the-counter medications or supplements.”

For this reason, Jacinto-Dearing says it’s crucial that patients make their healthcare providers and pharmacists aware of all the medications and supplements they’re taking, both prescription and non-prescription. She also suggests not stopping any of your current medications in order to start taking Paxlovid without reaching out to your doctor or pharmacist first.

Where can I get Paxlovid?

While the initial supply of Paxlovid was very limited — only 65,000 treatment courses at the time the EUA was issued – it’s now widely available in most pharmacies and health clinics across the country.

Additionally, the White House launched a test-to-treat program that allows people to both get tested for COVID-19 and receive Paxlovid on the spot at no cost. You can find a list of available test-to-treat locations here.

What are my other options?

In addition to Paxlovid and monoclonal antibody treatments, the FDA issued an EUA for Merck’s oral antiviral Lagevrio® (molnupiravir) to treat adults with mild-to-moderate COVID-19 who are at high risk of severe disease. While there are no known medication interactions with Lagevrio at this time, the clinical trial found the antiviral treatment cut the risk of hospitalization and death by 30% within five days of when symptoms begin.

That’s significantly less effective than Paxlovid, which, at the time of the clinical trial in 2021, cut the risk by 88%. A more recent study by the CDC found that adults who took Paxlovid had a 51% lower hospitalization rate than those who didn’t.

Working with your care team

The release of Paxlovid is still a game-changer in the fight against COVID-19, but because of the risk for serious medication interactions, taking the antiviral is a decision your entire care team needs to make together.

If your prescription plan include Express Scripts® Pharmacy, our specially trained pharmacists are here for you 24/7 to answer all your questions. They can work with your doctor to decide if Paxlovid, or any new medication, is right for you.


Updated: January 26, 2023

Posted date: February 09, 2022

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