How to Manage Drug Interactions With Paxlovid for COVID

Marcia Frellick

May 20, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Misinformation about nirmatrelvir/ritonavir (Paxlovid, Pfizer) for treating mild-to-moderate COVID-19 in patients at high risk for severe disease is feeding misunderstanding among prescribers and patients, two experts from the Infectious Diseases Society of America (IDSA) said on Friday.

They briefed reporters on potential drug interactions and uncommon cases of a "rebound" effect with the drug, which was granted emergency use authorization by the US Food and Drug Administration last December for patients at least 12 years old.

Jason C. Gallagher

The drug combination works "like a pair of scissors chopping up proteins that are made as the virus replicates inside of cells. Inhibiting that enzyme leads to the cessation of replication,” said Jason C. Gallagher, PharmD, Temple University School of Pharmacy, Philadelphia, Pennsylvania.

That's important because other treatments that target the spike protein, such as monoclonal antibodies, can lose their efficacy as the virus changes. He said that while that's not impossible for Paxlovid, "we have not seen variants emerging that are resistant to it."

Potential Drug Interactions

IDSA recently published updated guidance on potential interactions between Paxlovid and the top 100 drugs, and important considerations for prescribing.

"There is a concern that people have not been prescribing it because of fear of these interactions," Gallagher said, explaining that, while in some cases those fears may be valid, in many instances the interaction is manageable.

One example is in two popular statins for heart disease, lovastatin and simvastatin.

"That's an interaction that can be managed by holding [those drugs] for the 5 days that someone receives Paxlovid," he said.

Misinformation is also circulating about distribution status of Paxlovid, Gallagher said.

"We're in a very different state from that standpoint than we were a month or 2 months ago," he said, adding that it is widely available in not all but a large number of pharmacies throughout the United States.

He emphasized the importance of drug reconciliation, as many patients will go to a different pharmacy for Paxlovid than they might for their usual prescriptions, so without a full accounting of prescriptions and supplements potential interactions may be missed.

Important Interactions to Watch

Dr Melanie Thompson

Melanie Thompson, MD, cochair of the HIVMA/IDSA HIV Primary Care Guidance Panel, highlighted some classes of drugs to watch, among them the antiarrhythmics, most of which are contraindicated with Paxlovid.

There are also important interactions with a number of cancer drugs, and consults with oncologists will be critical, she said.

"Likewise, people who have had transplants are likely to be on drugs that have significant ritonavir interactions," Thompson said.

People on ergot drugs for migraine cannot take Paxlovid, she said, and "people who take colchicine for gout have to be very careful."

She said it's better not to use colchicine while taking Paxlovid, as it is contraindicated, "but it can be managed in certain circumstances with substantial dose reduction."

A number of mental health drugs can be managed with Paxlovid, Thompson said. For the antipsychotic drug quetiapine, (Seroquel), a "substantial decrease in dose is required."

Viagra for ED Can Be Managed

Use of Viagra depends on why it's being used, Thompson said. If it's used for pulmonary hypertension, it is used at a very high dose and that is contraindicated. But if used for erectile dysfunction, the dose needs to be managed when people are on Paxlovid.

She said prescribers must know the kidney function of patients.

"There is a dose reduction that is required if people have impaired kidney function but below a certain level of function, which is 30 mL/min, it's not recommended to give Paxlovid."

Thompson highlighted two other websites for thorough, printable information on drug-drug interactions with Paxlovid: the University of Liverpool's drug interaction checker and a printable handout from the University of Waterloo in Ontario, Canada.

"We need a 24/7 clinician hotline for Paxlovid to really make it accessible," she said.

No Data Yet on "Rebound" Effect

As to a few recent reports of a "rebound" effect, of people developing COVID-19 symptoms after completing a course of Paxlovid, there is not enough data yet to determine a clear pattern or cause.

Thompson said, "all we have are anecdotal data." Current questions for study include whether the 5-day course is not long enough, she said, and whether people more at risk should be given a second course of Paxlovid if they do rebound.

Gallagher said it's important to remember that the therapy goal of the drug is to prevent hospitalizations and deaths, and while any rebound is problematic, "it's possible the use of the medication has already saved a life."

Gallagher and Thompson report no relevant financial relationships.

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.

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