While the omicron surge continues to wreak havoc on a pandemic-weary society, the first antiviral pill for Covid-19 offer much-needed protection for those at risk of severe infection.

However, many people who are prescribed Pfizer or Merck’s new drugs will need to be closely monitored by doctors and pharmacists, and experts warn that the antivirals may not be safe for everyone.

The Food and Drug Administration approved Pfizer’s Paxlovid for mild to moderate Covid in children as young as 12 who have underlying conditions like heart disease or diabetes that increase the risk of hospitalization and death from the coronavirus.

However, one of the antiviral cocktail’s two agents could have serious or life-threatening interactions with common drugs including statins, blood thinners, and antidepressants. Paxlovid is also not recommended by the FDA for patients who have severe kidney or liver problems.

Because of concerns regarding molnupiravir’s potential side effects, the FDA has limited its use to adults and only in situations where other approved treatments, such as monoclonal antibodies, are unavailable or not “clinically appropriate.”

The Paxlovid combination contains two tablets of the antiviral nirmatrelvir and one tablet of ritonavir, which has long been utilized in HIV regimens as a boosting agent. Ritonavir inhibits CYP3A, a crucial liver enzyme involved in the metabolism of numerous drugs, including nirmatrelvir. Ritonavir reduces the body’s degradation of the active antiviral and helps it stay at a therapeutic level for longer in Paxlovid treatment.

Paxlovid’s remarkable success in clinical trials was almost certainly due to the boosting effect.

When Paxlovid is used with other medications that are also processed by the CYP3A enzyme, the main concern is that the ritonavir component will increase the toxic levels of the co-administered meds.

Complicating matters, the drugs that represent a risk of interaction are commonly provided to those who are at the highest risk of Covid due to other medical issues.

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 are just a few examples of the medications.

“Some of these potential interactions are not trivial, and some pairings have to be avoided altogether,” says 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.”

The FDA has released a complete list of drugs that may interact negatively with ritonavir in its Paxlovid fact page, including those that should not be taken with Covid antivirals.

Many drug interactions, however, are tolerable, according to pharmacists, and should not prevent most people from using 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,” adds 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.” 

Dr. William Werbel, an assistant professor of medicine at Johns Hopkins University, recommended people at high risk of Covid-19 complications to talk to their doctors and a knowledgeable pharmacist about possible changes to their drug regimens if they need Paxlovid — even before becoming infected with the virus.

Anyone seeking Paxlovid, which must be administered within five days of the onset of symptoms, should inform their prescribers and pharmacists of all other prescriptions and over-the-counter supplements they are currently taking, according to Anderson.

Some medications, such as some statins, are likely safe to discontinue using while taking the Covid tablets, according to Anderson. For example, it may be preferable to continue taking certain blood thinners but reduce the dosage. Paxlovid interacts with some heart rhythm medications.

Some anti-seizure drugs, as well as the herbal supplement St. John’s Wort, can increase the metabolic activity of liver enzymes, lowering Paxlovid levels in the body. They should not be taken together with Paxlovid, according to the FDA.

Experts are optimistic that the danger of bad interactions with other medications is low because the Paxlovid treatment is brief – 30 pills, given three times a day for five days.

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

If a drug’s potential interaction with Paxlovid is too risky, Anderson recommends GlaxoSmithKline’s sotrovimab, a safe and effective alternative Covid-19 therapy. Sotrovimab is the only authorized monoclonal antibody treatment that reliably neutralizes the virus’s omicron variant, according to research. Otherwise, molnupiravir, an antiviral with significantly lesser efficiency than Paxlovid or sotrovimab, is an alternative.

Despite the risks of using Paxlovid alongside other prescription medications, scientists are optimistic about the drug’s future.

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

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