As the omicron surge pummels a pandemic-weary nation, the first antiviral pills for Covid-19 promise desperately needed protection for people at risk of severe disease. However, many people prescribed Pfizer’s or Merck’s new medications will require careful monitoring by doctors and pharmacists, and the antivirals may not be safe for everyone, experts caution.

Paxlovid, Pfizer’s Covid-19 pill, is manufactured in Ascoli, Italy.Pfizer via Reuters

The Food and Drug Administration authorized Pfizer’s Paxlovid for mild to moderate Covid in people as young as 12 who have underlying conditions that raise the risk of hospitalization and death from the coronavirus, such as heart disease or diabetes. However, one of the two drugs in the antiviral cocktail could cause severe or life-threatening interactions with widely used medications, including statins, blood thinners and some antidepressants. And the FDA does not recommend Paxlovid for people with severe kidney or liver disease.

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Because of experts’ concerns about the potential side effects of Merck’s molnupiravir, the FDA has restricted its use to adults and only in scenarios in which other authorized treatments, including monoclonal antibodies, are inaccessible or are not “clinically appropriate.”

The Paxlovid cocktail consists of two tablets of the antiviral nirmatrelvir and one tablet of ritonavir, a drug that has long been used as what is known as a boosting agent in HIV regimens. Ritonavir suppresses a key liver enzyme called CYP3A, which metabolizes many medications, including nirmatrelvir. In the case of Paxlovid treatment, ritonavir slows the body’s breakdown of the active antiviral and helps it remain at a therapeutic level for longer.

The boosting effect was likely to have been crucial in driving Paxlovid’s high effectiveness in clinical trials.

When Paxlovid is paired with other medications that are also metabolized by the CYP3A enzyme, the chief worry is that the ritonavir component may boost the co-administered drugs to toxic levels.

Complicating matters, the drugs that pose interaction risks are widely prescribed to people at the greatest risk from Covid because of other health conditions.

The medications include, but are not limited to: blood thinners; anti-seizure medications; drugs for irregular heart rhythms, high blood pressure and high cholesterol; antidepressants and anti-anxiety medications; immunosuppressants; steroids (including inhalers); HIV treatments; and erectile dysfunction medications.

“Some of these potential interactions are not trivial, and some pairings have to be avoided altogether,” said Peter Anderson, a professor of pharmaceutical sciences at the University of Colorado Anschutz Medical Campus. “Some are probably easily managed. But some we’re going to have to be very careful about.”

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In its fact sheet about Paxlovid, the FDA has published a detailed list of medications that may interact harmfully with ritonavir, including those that should not be paired with the Covid antivirals.

However, pharmacists stress that many of the drug interactions are manageable and that they should not preclude most people from taking Paxlovid.

“Pharmacists are highly trained experts in medication safety and monitoring and are an excellent source of information and advice about interactions between medications and also supplements and herbal products,” said Emily Zadvorny, a clinical pharmacist who is the executive director of the Colorado Pharmacists Society. “They will help determine if a significant interaction exists and devise solutions to mitigate the interaction if possible.” 

‘A breakthrough drug’

The good news is that health care providers have experience navigating ritonavir’s use among people with HIV — a group that often takes medications for other health conditions, in addition to antiretroviral therapy.

Dr. William Werbel, an assistant professor of medicine at Johns Hopkins University who specializes in transplant infectious diseases, advised people at high risk of Covid-19 complications to talk to their health care providers, as well as a savvy pharmacist, about changes they could make to their drug regimens should they need Paxlovid — even before they become infected with the virus.

Anyone seeking Paxlovid, which must be prescribed within five days of the first symptoms, should be sure to let their prescribers and pharmacists know the complete lists of other medications and over-the-counter supplements they are taking, Anderson said.

Some medications, such as particular statins, are most likely safe to stop taking during treatment with the Covid pills, Anderson said. For example, it might be better to stay on certain blood thinners but to lower the doses. Some heart rhythm drugs cannot be taken with Paxlovid.

Conversely, some anti-seizure medications can boost liver enzymes’ metabolic action and thus lower the body’s Paxlovid levels, as can the herbal supplement St. John’s Wort. The FDA warned that they should not be combined with Paxlovid.

Because the Paxlovid treatment is brief — 30 pills, taken as three pills twice a day for five days — experts are hopeful that the risk of adverse interactions with other medications is low.

“Five days of interactions is not a big deal for the majority of drugs,” said Jason Gallagher, a clinical pharmacy specialist in infectious diseases at Temple University Hospital in Philadelphia.

If a drug’s potential interaction with Paxlovid poses too much of a risk, Anderson said, a safe and effective alternative Covid-19 therapy would be GlaxoSmithKline’s sotrovimab — the sole authorized monoclonal antibody treatment that research indicates reliably neutralizes the omicron variant of the virus. Otherwise, the antiviral molnupiravir is an option, albeit one with a much lower efficacy than either Paxlovid or sotrovimab. 

Even with the concerns about taking Paxlovid with other prescription medications, experts are excited about the drug’s potential.

“Paxlovid is a breakthrough drug,” Anderson said. “This could make a real difference in the pandemic by making an effective Covid treatment available to many people.”

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