Paxlovid

Paxlovid or your statin?

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Patients on some medications are sometimes told they can’t take Paxlovid. Is that the right move

An illustration depicting a balance scale. On one side of the scale, there's a blank pill bottle with no label, representing an unspecified medication. On the other side of the scale, there's a representation of a statin medication, shown as a pile of pills. The scale is evenly balanced, symbolizing a comparison or interaction, with one side featuring an unlabeled pill bottle. The setting is neutral, focusing solely on the scale, the unlabeled bottle, and the statin medication.

Scenario: You’re diagnosed with Covid-19. You’ve been taking a statin to lower your cholesterol for years. But you’re told that the statin has a potential interaction with Paxlovid, the blockbuster Covid antiviral that decreases hospitalizations and death. Should you temporarily stop taking that statin and take Paxlovid for 5 days to decrease your chances of a bad outcome due to Covid?

This question comes up a lot.

First, if you take any statin other than lovastatin, simvastatin, atorvastatin or rosuvastatin, the answer is easy. If you have high-risk conditions for Covid, you can add Paxlovid on top of those other statins without concern for any unsafe interactions.

But what if you take lovastatin(Altoprev),simvastatin (Zocor), atorvastatin (Lipitor) or rosuvastatin (Crestor)? Pfizer says that its drug Paxlovid can have drug-drug interactions with these medications, and that the combination could lead to unsafe muscle breakdown. That in turn could lead to kidney problems or even death (albeit that is exceedingly rare). Accordingly, the FDA advises patients to stop taking their lovastatin or simvastatin 12 hours before the first dose of Paxlovid, and to resume the statin 5 days after they’ve completed the 5-day antiviral course. For atorvastatin and rosuvastatin, the contraindication is less strong and the FDA says that clinicians should “consider” temporary discontinuation of these drugs, but only during the 5 days when Paxlovid is being taken.

However, it seems that a group of patients are not being prescribed Paxlovid because they take a statin. On Threads, 24% of respondents to an informal poll I posted said that they’d been told not to take Paxlovid because of a drug they take. Of those, 76% said the drug was either a statin, blood pressure medication, or a blood thinner. (On Twitter, I posted the same poll and it yielded similar results.)

Rather than telling their patients to hold their statin, blood pressure medication, or blood thinners for a week, many doctors are just not prescribing Paxlovid to patients on these medications. Yes, these drugs decrease the long-term risk of heart attacks or strokes. But by how much in a 5-10 day period? Enough to offset the benefits of Paxlovid in very high-risk populations?

Has anyone done a risk-benefit analysis on this?

If it is out there, I have not seen it.

So, fine, let’s do one ourselves!

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Let’s look at the choice between continuing to take a statin and Paxlovid. The decision really boils down to one question: Which is the greater, the decrease in Covid-19 mortality due to Paxlovid, or the increase in cardiovascular disease death resulting from skipping 5-10 days of a statin? Put another way, if Paxlovid decreases the percentage of people who die of Covid more than the statins decrease the percent of people who would die from a heart attack in the period they stopped taking them, the correct strategy would be to take Paxlovid and temporarily hold the statin.

We basically know the answer to these questions, though with Paxlovid, the benefit has changed (i.e., decreased) over time as the population has gained immunity to Covid.

What is the worst-case scenario for temporarily not taking a statin for 10 days? Let’s look at the group with the very highest cardiovascular risks—because if the analysis favors temporarily stopping their statin in favor of Paxlovid, so can everyone else. Research of people ages 65 and up who survived a recent major heart attack tells us that the 1-year mortality rate following the event is around 24%. While most of that 24% died within 6 months of the event (making the second 6 months much lower risk), we can conservatively assume that the post-heart attack mortality rate for the first year is around 0.66% every 10 days. Let’s just assume that all of the patients in these heart attack follow up studies were taking statins (most were), and that statins reduce the risk of another fatal heart attack by 25%. If we assume that stopping the statin immediately erases the entire benefit of taking the drug (which is not remotely true, but I’ll go with this just to be extremely careful in our analysis), the 10-day mortality rate would rise to 0.82%—that is, an increase of 0.16%.

Does Paxlovid decrease the risk of death in these patients by more than that? In the pre-vaccine era, the answer was not even close: yes, yes, a thousand times yes. The absolute reduction was more like 1% (and the relative reduction more likely 85%-100%). But today, an era in which everyone has been vaccinated, infected, or both, Paxlovid’s absolute benefit is far smaller. Yes, it still works for high-risk people, but the absolute effect has gone down dramatically. The first major study looking at Paxlovid during the vaccine era found that among people ages 65 and up, Paxlovid use was associated with a decrease in mortality from 0.39% to 0.08%—a decrease of 0.31%.

That means that even for extremely high-risk cardiovascular patients ages 65 and up—people who had recovered from a heart attack within the last year—the mortality increases of stopping a statin for 10 days might at most be around half of the mortality decrease associated with Paxlovid. And that’s if holding the statin for 10 days completely eliminates the patient’s lowered heart attack risk by virtue of their statin use. And for people more than a year out from their heart attacks? The hypothetical worst-case scenario mortality risk increase of holding that statin for 10 days would be just 0.07%.

Raw terms: The above numbers imply that for the population aged 65 and up we’re considering, around 1 in 608 people who survived a heart attack within the last year might die due to another heart attack during the 10 days of skipped statin doses, assuming the statin’s effect is all we’re giving it credit for (and, again, likely it’s a much smaller effect). For people more than a year out from their heart attack, holding the statin for a week might come with an increased mortality risk of around 1 in 1,460 people. Meanwhile, Paxlovid’s effect in similar patients would be associated with a decrease in mortality for around 1 in every 322 people who took it during the vaccine era.

Now if, you’re over age 65 and less than 6 months out from a heart attack (or recently had a coronary artery stent placed for very bad angina), skipping the statin might not be the right move. It depends on the situation, and also, just how much those missed statin doses actually matter (i.e., less than we said). Despite our conservative assumptions in the math above, the accrued benefit from taking a statin for months or years does not immediately fall to zero by skipping it for 5-10 days. Cholesterol levels take time to build up and to confer risk. What’s more certain is that as we progress from 6 months to a year out from a heart attack, the scale would seem to tip heavily in favor of Paxlovid, rather than staying on the statin instead.

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What about people who have not had a heart attack but are at risk of one? Their risk of skipping the statin is far, far lower. The analysis would so heavily favor Paxlovid that the math is not even worth doing.

Unfortunately, at least some doctors are getting this wrong on the ground. Of the few (but mighty) people who reached the third question in my Threads and Twitter polls (which asked “If the relevant drug [which prevented you from getting Paxlovid] was for anything cardiovascular, have you ever had a stroke or heart attack?), most said “No, but I am at risk.”

Le sigh!By far, the highest risk cardiovascular group are those who have already had a major heart attack. A bunch of patients who have far lower mortality risks than the ones we just decided can skip their statin for 10 days are apparently being told by their doctors that it’s too risky for them to skip their statin in favor of Paxlovid. Unless Paxlovid really does not work in vaccinated people at all (and we’ll finally get randomized clinical trial data on this later this year, I am led to believe), this is pretty bad decision science.

Now what about people under age 65? I have not done the analysis. The risk-benefit balance would hinge on how much Paxlovid helps younger people with high-risk conditions for Covid-19 and what their post-heart attack mortality risks are at any given time. The answer is not straightforward because on one hand, the benefit of Paxlovid is substantially smaller than older people with those same conditions (in fact, in that big study I mentioned above, the associated benefit for Paxlovid use among at-risk patients ages 40-64 was actually nil). On the other hand, the one-year mortality among heart attack survivors under age 65 may also be a lot lower. There are too many variables for me to plant a flag on this one.

Other meds. Lastly, there are many other medications that have possible interactions with Paxlovid. Some are related to heart disease, including blood thinners and blood pressure medications. For these, it also seems highly unlikely that skipping them for 5-10 days would be as dangerous as passing on Paxlovid among the truly high-risk population that benefits from it. The same analysis as above would also apply to those medications; the upshot is that the short-term risk of a fatal heart attack is just not that high, even among fairly recent heart attack survivors (that is, more than a few months out). Some drugs on the Paxlovid interaction radar include certain types of chemotherapy and drugs that prevent seizures. The list is not short and in some instances, the correct choice is not immediately obvious.

Decision science is not easy.

Each decision, made properly, should reflect a careful comparison of the risks of temporarily stopping one medication against the opportunity costs of foregoing Paxlovid. To make the right call, doctors have to know how much the risk increases on one side of the ledger, and how much Paxlovid decreases risk for the patient in front of them, on the other.

How many doctors have the time—let alone up-to-date information to draw on—to get these decisions right? Very few. It’s not their fault. There are simply too many variables to keep up with. Down the road, this will be a perfect application for AI. At the moment, though, there’s no reliable tool for these assessments. Your doctor may not have exact numbers to cite when you ask about this. But it’s still good to ask if you have concerns. Sometimes a good question is enough to get us thinking

Paxlovid, Advertised for Mass Use, Has Contraindications With Hundreds of Drugs

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COVID-19 treatment pill Paxlovid in boxes at Misericordia hospital in Grosseto, Italy, on Feb. 8, 2022. (Jennifer Lorenzini/Reuters)

COVID-19 treatment pill Paxlovid in boxes at Misericordia hospital in Grosseto, Italy, on Feb. 8, 2022. (Jennifer Lorenzini/Reuters)

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One of the most robustly campaigned and well-known drugs for treating COVID is Paxlovid. Yet the drug’s limited clinical studies and numerous drug interactions raise questions of safety for COVID patients.

Approved for Emergency Use Authorization (EUA) in December 2021 and promoted by the Food and Drug Administration (FDA), health officials, and politicians alike, Paxlovid is fast becoming the one-track drug for early COVID treatment.

Paxlovid’s EPIC-HR clinical trial, sponsored by Pfizer, revealed that those who took the drug were 89 percent less likely to develop severe COVID than those who took a placebo. Those who took Paxlovid also had lower quantities of the SARS-CoV-2 virus detected after five days of treatment.

With such impressive results, the FDA made swift moves to promote the prescription of Paxlovid—extending to pharmacists the authority to prescribe Paxlovid beginning in July 2022.

This raised concerns and disapproval from some clinicians.

Though laws in some states allow pharmacists to prescribe a limited number of drugs, such as contraceptives and naloxone, prescribing medication is primarily the responsibility of doctors.

Diagnostic and interventional cardiologist Dr. Jack Askins from Wichita Heart Center told The Epoch Times that it was unprecedented for pharmacists to be given authority to prescribe EUA medication.

Physicians are familiar with their patient’s medical histories, intolerances, allergies, and other medications the patient is taking and would be able to avoid potentially dangerous adverse effects from drug interactions. Though pharmacists can access medical records electronically, a study wrote that “pharmacists’ access to patient information is not adequate for competent prescribing.”

The FDA has required pharmacists who prescribe Paxlovid to have access to the patient’s medical history and a list of all the drugs the patient is taking.

Pharmacists taking on the role of physicians through their authority to prescribe Paxlovid is only one aspect of clinicians’ concerns about the drug; the more significant problem is a multitude of potential drug interactions.

Epoch Times Photo
A Pfizer technician handles the company’s COVID-19 pill, known as Paxlovid, in a file photograph. (Pfizer via AP)

Drug Mechanism and Interactions

Askins wrote in his Substack article published Oct. 16, 2022, that he had “never seen a drug with that many drug interactions and potential incompatibilities.”

Paxlovid can interact with at least 43 different classes of drugs and over 550 active drug ingredients. Some of these interactions can be severe and potentially dangerous, some mild.

A single dose of Paxlovid contains three pills: two pink and one white. The pink pills are nirmatrelvir tablets, patented by Pfizer; the white pill is ritonavir, a medication for HIV.

Nirmatrelvir is an antiviral; it works early during COVID-19 infections by stopping the virus from replicating.

Nirmatrelvir targets a viral protein in the SARS-CoV-2 virus that is common to all coronaviruses. This viral protein, known as Mpro, helps to assemble the viral components into an infectious virus. Nirmatrelvir stops the action of Mpro by attaching itself to it so that the viral protein can no longer form functional viruses.

Ritonavir is also an antiviral, but it does not target coronaviruses. The job of ritonavir is to boost the actions of nirmatrelvir.

When ingested, ritonavir will bind and stop the action of an enzyme named cytochrome P4503A4 (CYP3A4) and prevent the body’s own proteins from breaking down and metabolizing nirmatrelvir.

Problems arise from here.

Many classes of drugs work by blocking or activating the actions of CYP3A4. If a person takes these drugs while taking Paxlovid, the other drugs’ effects can be neutralized or increased, both potentially dangerous.

According to a statement published by the FDA, Paxlovid interacts with various drugs, including cardiovascular drugs, narcotics, antipsychotics, anticoagulants, anti-HIV drugs, and many others.

“This contraindication list is significant because it means many patients with heart conditions, arrhythmias, high cholesterol, epilepsy, depression, and many other common diseases in supposedly high-risk COVID-19 patients cannot take the ‘game-changer,’” emergency doctor Dr. John Hughes wrote to The Epoch Times.

A particularly paradoxical aspect of Paxlovid is that the clinical data shows it seems to work the best for older adults. However, people over 65 are also most at risk of drug interactions, as they are likely to be taking multiple prescription drugs.

This was demonstrated in a a recently published study that evaluated over 62,000 hospitalized COVID-19 patients in Paris. These hospitalized patients received a positive COVID test between January 2020 and November 2021. Given that Paxlovid was authorized and marketed in 2022, none of the patients received Paxlovid.

However, even if Paxlovid had been available, many would likely not have been able to use the medication, as half  (50.7 percent) of the patients were on other medications that would contraindicate with the antiviral, or had organ deficiencies.

Askins noted that many of the anticoagulants and cardiovascular drugs he prescribes for his patients would interact with Paxlovid, and thus one of the drugs would need to be excluded.

“Some of the antiarrhythmic drugs can be dangerous if given concurrently with the Paxlovid,” Askins said.

In antiarrhythmic drugs with the active ingredient amiodarone, dronedarone, flecainide, propafenone, or quinidine, Paxlovid can increase the pharmacologic effects of these drugs. Since antiarrhythmic drugs slow down and reset heart rates, an enhanced effect of these drugs can lead to lower heart rates, reduced blood pressure, and cardiac arrest.

In certain anticoagulants with the active ingredient apixaban, dabigatran, or rivaroxaban, Paxlovid increases the risk of bleeding if used concomitantly.

Paxlovid can increase the effects of antipsychotics such as lurasidone and pimozide, both prescribed for schizophrenia, and may lead to potentially fatal cardiac arrhythmias.

Askins noted that Paxlovid also enhances the effects of fentanyl, a powerful opioid. Fentanyl’s potency makes the drug extremely dangerous when overdosed, as it can cause death from reduced breathing.

The FDA has recommended that patients either go off their usual medications or take Paxlovid in conjunction with their medications, depending on the severity of the interactions. Patients’ physicians should observe them for any adverse effects of taking Paxlovid.

In the FDA’s statement “Fact Sheet for Healthcare Providers,” the agency recommended that physicians follow patients’ medical history; for prescribing pharmacists, only those with at least 12 months of a patient’s medical history can prescribe.

However, Askins has become aware that some of his emergency department colleagues may prescribe Paxlovid without adequate knowledge of the potentially dangerous drug contraindications.

Hughes also said that some clinicians are unaware of Paxlovid drug interactions.

“Just last week, an elderly man with a serious heart arrhythmia on amiodarone came to my ER to get Paxlovid. But I couldn’t prescribe it because of the medication he was on,” Hughes wrote to The Epoch Times, “His cardiologist hadn’t even paid attention to his medication list before sending him to the ER.”

“For a disease killing almost nobody now, a severe drug interaction with heart and other common medications begs for a serious risk-benefit analysis,” Hughes added.

Askins highlighted that the past two years of extensive green-lighting of experimental drugs by the FDA through EUAs have made experimental drugs and medical interventions a “new normal” for clinicians and patients.

“I think one of my big concerns about the last few years is this emergency use authorization,” said Askins.

Before 2020, EUA was rarely implemented. But since the pandemic, the FDA has authorized EUAs at least 600 times on vaccinations, pharmaceuticals, medical equipment, and tests.

Apart from the drug interactions, Paxlovid is not recommended for people with liver or kidney insufficiency as it can cause toxicity.

Pharmacist Michael Lam said that Paxlovid’s side effect of dysgeusia, known as “Paxlovid mouth,” also seems to impact patients’ drug adherence.

The ritonavir in the Paxlovid leaves a bitter or metallic taste in the mouth that can last for hours.

Lam took Paxlovid when he developed COVID and went off it after two days. “You take it two times a day,” described Lam. “So it lasted like six hours in a day [during which] you have that bitterness in your mouth.”

The Pfizer clinical trials showed that 5.6 percent of the people reported dysgeusia to describe the altered taste. However, Lam wondered if the actual proportion of people experiencing this side effect is higher.

Effectiveness: More Research Needed

Despite being the “go-to” drug for COVID-19, the actual effectiveness of Paxlovid is questionable.

The clinical study that granted Paxlovid’s approval came from the abovementioned EPIC-HR study. The study was conducted with unvaccinated and previously uninfected COVID patients with a high risk of severe COVID disease.

Given that 68 percent of the American population has now been vaccinated and most people have been exposed to the virus through previous infections, the group studied in the Paxlovid trial does not represent most of the current population.

The study was conducted from July 2021 to December 2021, when the dominant COVID-19 strain was Delta, but the common strain now is Omicron, known to be the least pathogenic of all COVID-19 viral strains.

Pfizer later conducted another study from August 2021 to July 2022, likely coinciding with the Omicron wave.

This study was named EPIC-SR and was conducted on people with a “standard risk” of developing severe COVID. The study also accepted vaccinated people and would be the most reflective of the current population. Yet it did not meet its primary endpoint, which is sustained alleviation in COVID symptoms for four days after a five-day Paxlovid treatment.

The trial was terminated in June 2022, as even the secondary endpoint could not be met. The secondary endpoint was reduced relative risk of hospitalization and deaths, but standard risk patients have a very low risk of hospitalizations and deaths, and the study could not reach a statically significant outcome.

“That’s what it was, basically a fail,” said Lam. “In terms of efficacy, it is debatable for COVID.”

Researchers conducting a study in Israel on the effects of Paxlovid for severe Omicron infections found that in the group that took Paxlovid, only patients who were 65 years of age or older had significantly lower rates of hospitalizations and deaths.

For people younger than 65, the study found no benefits. This finding raises further questions on the actual effectiveness of the drug.

Other studies conducted in Hong Kong and Israel also found that Paxlovid was associated with lower risks of hospitalization and death. In each of these studies, over 50 percent of the patients on Paxlovid were over 60 years of age (1, 2).

Therefore, more research is needed to determine the drug’s effectiveness, especially in younger people.

Askins and Hughes also noted that politicians and health agency officials, including President Joe Biden and the head of the National Institute of Allergy and Infectious Diseases (NIAID), Dr. Anthony Fauci, experienced reinfections with COVID-19 after taking Paxlovid, highlighting the risk of possible rebounds.

The Centers for Disease Control and Prevention (CDC) issued a rebound warning on Paxlovid on May 24, 2022. Since then, studies that evaluate rebound incidence have dished out contradicting and varied results.

A Mayo Clinic study published in June 2022 reported that less than one percent of patients taking Paxlovid experienced rebound symptoms.

One pre-print (not yet peer-reviewed) report published in June 2022 described a 3.5 to 5.4 percent rebound rate in people who took Paxlovid.

Another pre-print study published in November 2022 found that of 127 patients treated with Paxlovid, 14 percent tested positive for COVID after a previous negative test, while in the group of patients who did not take Paxlovid, this number was 9 percent.

Additionally, among the people who took Paxlovid, around 19 percent reported a rebound in COVID symptoms. This number was 7 percent in the control group who did not take Paxlovid.

Nevertheless, Askins said that most of his emergency physician colleagues report that patients who take Paxlovid within the first five days of a COVID infection generally experience a symptom alleviation by the third or fourth day after starting the drug.

Lam and Hughes each noted that given Omicron is significantly less severe than previous Alpha and Delta strains, the question is if patients are getting better from the drug or because the disease is so mild. Most with Omicron “get better in three to four days regardless of whether they took anything for it,” stated Hughes.

Gastroenterologist Dr. Sabine Hazan has told The Epoch Times that, in her clinic, for people with a healthy constitution, rather than using medications, she would primarily focus on supplementing their immune system with vitamins C and D so patients can fight off the infection themselves.

Holistic and integrative medicine physician Dr. Saleeby Yusuf has recommended that COVID patients who turn to supplements should use pharmaceutical-grade versions rather than easily accessible supplements from supermarkets, as the pharmaceutical-grade versions would generally be more effective with greater bioavailability.

From Positive to Negative to Positive Again—The Mystery of Why COVID-19 Rebounds in Some Patients Who Take Paxlovid.

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13 Things To Know About Paxlovid, the Latest COVID-19 Pill

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Yale experts answer commonly asked questions about the oral antiviral medication.

close up of Paxlovid, a COVID-19 pill

[Originally published: March 10, 2022. Updated: May 12, 2022] 

Note: Information in this article was accurate at the time of original publication. Because information about COVID-19 changes rapidly, we encourage you to visit the websites of the Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), and your state and local government for the latest information.

Paxlovid is the latest COVID-19 treatment that’s been all over the news. The drug was granted an emergency use authorization (EUA) by the Food and Drug Administration (FDA) in December for anyone ages 12 and older who weighs at least 88 pounds, and is at high risk for severe disease. Pfizer recently began Phase 2 and 3 trials in children and teens ages 6 to 17. 

Paxlovid is an oral antiviral pill that can be taken at home to help keep high-risk patients from getting so sick that they need to be hospitalized. So, if you test positive for the coronavirus and a health care provider writes you a prescription, you can take pills at home and lower your risk of going to the hospital.

The drug, developed by Pfizer, has a lot of positives: It had an 89% reduction in the risk of hospitalization and death in the clinical trial that supported the EUA, a number that was high enough to prompt the National Institutes of Health (NIH) to prioritize it over other COVID-19 treatments; it’s cheaper than many other COVID-19 drugs (it’s provided for free by the U.S. government while there is a public health emergency); and, perhaps most reassuring, it is expected to work against the Omicron variant.

“I think it is the beginning of a ‘game-changer,’” says Scott Roberts, MD, a Yale Medicine infectious diseases specialist. “It’s really our first efficacious oral antiviral pill for this virus. It shows clear benefit, and it really can prevent hospitalization and death in people who are at high risk.”

It’s important to note that Paxlovid (the brand name for the drug, which is made up of two generic medications—nirmatrelvir and ritonavir) isn’t the only pill available to treat COVID-19. The FDA also granted an EUA in December to a pill from Merck called molnupiravir (Lagevrio), but some studies suggest that molnupiravir has only a 30% reduction in the risk for hospitalization and death from COVID-19. 

And as far as convenience, this medication is considered an improvement over treatments like remdesivir (approved by the FDA in October 2020), which is administered by intravenous (IV) injection.

We asked Yale Medicine infectious diseases experts common questions about Paxlovid. Below are their responses.

1. How does Paxlovid work?

Paxlovid is an antiviral therapy that consists of two separate medications packaged together. When you take your three-pill dose, two of those pills will be nirmatrelvir, the drug that inhibits the SARS-CoV-2 protein from replicating. The other is ritonavir, a drug that was once used to treat HIV/AIDS but is now used to boost levels of antiviral medicines. 

As a COVID-19 treatment, ritonavir essentially shuts down nirmatrelvir’s metabolism in the liver, so that it doesn’t move out of your body as quickly, which means it can work longer—giving it a boost to help fight the infection.

2. When should I take Paxlovid?

You have to take Paxlovid within five days of developing symptoms.

Like all antivirals, Paxlovid works best early in the course of an illness—in this case, within the first five days of symptom onset, says Jeffrey Topal, MD, a Yale Medicine infectious diseases specialist who is involved in determining COVID-19 treatment protocols for Yale New Haven Hospital patients.

“Once you’ve been ill with the virus for more than a week, the damage done to the body in a severe case can’t be undone by the antiviral,” he says.

3. How often do I take Paxlovid?

You take three Paxlovid pills twice daily for five days for a full course that adds up to 30 pills. It helps that the pills are packaged in a “dose card,” basically a medication blister pack that allows you to punch out the pills as needed. 

4. Is Paxlovid similar to Tamiflu?

“I think it’s a good comparison,” says Dr. Roberts. Tamiflu is an antiviral drug that reduces flu symptoms. Both are prescription-only oral antiviral pills given early in illness.

Tamiflu is taken twice a day for five days, and it must be started within 48 hours of flu onset. “When you give a patient Tamiflu beyond that, it doesn’t really change the course of their flu,” Dr. Roberts says.

But there are also differences between the two, starting with the way they were studied, Dr. Topal adds. Researchers showed that Paxlovid can prevent hospitalization and death. But since influenza causes fewer severe cases, clinical trials focused on whether Tamiflu could shorten the length of flu illness—which it did, he says.

5. Can anyone get a Paxlovid prescription?

The FDA authorized Paxlovid for people ages 12 and older who weigh at least 88 pounds. But in order to qualify for a prescription, you must also have had a positive COVID-19 test result and be at high risk for developing severe COVID-19. 

That means you must either have certain underlying conditions (including cancer, diabetes, obesity, or others) or be 65 or older (more than 81% of COVID-19 deaths occur in in this group). The more underlying medical conditions a person has, the higher their risk for developing a severe case of COVID-19, according to the CDC.

The hope is that the restrictions on who can take Paxlovid will be relaxed over time. The FDA granted the EUA in December, just as a staggering number of people were infected with Omicron and the need for care skyrocketed, leading to supply issues.

6. How well does Paxlovid work?

When it applied for FDA authorization, Pfizer presented data from a clinical trial conducted between mid-July and early December in 2021. The data showed that participants (all of whom were unvaccinated) who were given Paxlovid were 89% less likely to develop severe illness and death compared to trial participants who received a placebo. (While the recommendation is to take Paxlovid within five days of symptom onset, participants in the clinical trial took the drug within three days.)

Scientists will continue to study the drug’s effectiveness as it is used to treat patients in the real world.

7. What do we know about how Paxlovid works in kids?

Pfizer launched a clinical trial in March to study the safety and efficacy of Paxlovid in children and teenagers ages 6 to 17 who have COVID-19 symptoms and test positive for the virus, and who are neither hospitalized nor at risk for severe disease.

While Paxlovid is authorized for use in adolescents and teenagers ages 12 and up, and weighing at least 88 pounds, that age group wasn’t tested in the original clinical trial. But because many children reach 88 pounds—considered to be an adult weight—the FDA has allowed extensions of EUAs for medications such as monoclonal antibodies and remdesivir in younger age groups, adds Dr. Topal.

“Based on the pharmacokinetics of the drugs in Paxlovid, the differences in metabolism and excretion—liver and kidney function specifically—of these drugs in this age group are thought to be similar to that of adults,” Dr. Topal says.

8. Does Paxlovid work against Omicron?

Paxlovid’s clinical trials took place before Omicron became predominant, but Pfizer says the drug works against the highly contagious variant. Three laboratory-based studies claim to back this up—two of those studies were conducted by Pfizer, while the third was done by Pfizer in partnership with the Icahn School of Medicine at Mount Sinai. These studies have not yet been published in peer-reviewed medical journals.

9. What are the side effects from Paxlovid?

Most people who take Paxlovid should not experience serious side effects, explains Dr. Roberts. “Paxlovid is usually very well-tolerated,” he says. Common side effects, which are usually mild, include:

  • Altered or impaired sense of taste
  • Diarrhea
  • Increased blood pressure
  • Muscle aches

Since Paxlovid is cleared by the kidneys, dose adjustments may be required for patients with mild-to-moderate kidney disease, explains Dr. Topal. “For patients with severe kidney disease—or who are on dialysis—or those with severe liver disease, Paxlovid is not recommended; the levels of the drug can become too high and could cause increased side effects,” he says. 

It’s worth noting that Paxlovid is still being studied, so it is possible that all of the risks are not yet known. (The FDA has provided a fact sheet on Paxlovid with a full list of known side effects.)

10. Can I take Paxlovid if I’m taking other medications?

There is a long list of medications Paxlovid may interact with, and in some cases, doctors may not prescribe Paxlovid because these interactions may cause serious complications.

The list of drugs that Paxlovid interacts with includes some organ anti-rejection drugs that transplant patients take, as well as more common drugs like some used to treat heart arrhythmias. Paxlovid also decreases the metabolism of anticoagulants, or blood thinners, that many older adults depend on, driving up levels of those medications in the body to a point where they are unsafe, Dr. Topal explains.

It also interacts with cholesterol-lowering medications like Lipitor, but that’s less challenging for patients to overcome. “If you stop taking your Lipitor for five days, nothing bad is going to happen,” he adds.

If you are pregnant or breastfeeding, the FDA recommends discussing your options and specific situation with your health care provider, since there is no experience using the drug in these populations. If you could become pregnant, it’s recommended that you use effective barrier contraception or do not have sexual activity while taking Paxlovid. 

11. What is the rebound effect of Paxlovid?

There have been reports of a “rebound” of COVID-19 symptoms in some people who have completed the five-day course of Paxlovid; in those cases, symptoms have recurred four or five days after completing the treatment. Some have also reported having a positive COVID-19 test after being treated with the drug. Pfizer had said that in the clinical trial for Paxlovid, several participants appeared to have a rebound in virus levels “around day 10 or day 14,” although this also occurred in some people who were given a placebo.  

“This is being closely investigated and we should have more guidance soon,” says Dr. Roberts. “The hypothesis is that the immune system didn’t have a chance to see the full extent of the virus, since Paxlovid suppressed replication early in disease,” he says.

There is currently no evidence to support a second course of Paxlovid in these situations, but scientists are studying the effects of longer treatment durations, longer periods of isolation, and other ways of managing the problem, he adds.

For anyone who experiences a rebound, Pfizer recommends reporting it to them on its portal for adverse events associated with Paxlovid.

12. If I’m not eligible for Paxlovid, is there something else I can take?

There are other therapies for COVID-19, and anyone who cannot take Paxlovid—perhaps because it would interact with another medication—should talk to their doctor about the best approach for their situation.

13. Do I still need to be ‘up to date’ on vaccination if Paxlovid is available?

Vaccination remains a key part of prevention, even as more drugs become available, says Dr. Topal. He pictures prevention as an upside-down pyramid. Vaccination, mitigation efforts, such as masking, and testing would be at the base—and medications at the top point.

“Early testing is key to making these drugs work,” he says. “It’s always been the Achilles’ heel of these antiviral drugs that most people don’t get tested—or they don’t have access to testing.”

He encourages taking a test even if you think you only have a cold or allergies—and if you can get one. “Home testing is a huge part of the way to really ‘operationalize’ these medications,” he says, adding that while home tests may not be as highly sensitive as the laboratory-based polymerase chain reaction (PCR) tests, they are still very helpful in making a diagnosis.

Dr. Topal says people also should remember that Paxlovid, even with its high efficacy, is not perfect, and even if it were, viruses can mutate and develop resistance to antiviral medications. “Will some people still be hospitalized? Yes—no medication is perfect,” he says. “But for many high-risk patients, this medication can really reduce that risk.”

If you are experiencing symptoms of COVID-19 and think you are eligible for a treatment, you can visit the government Test-to-Treat Locater. You can use the site to search for the places near you where you can fill a COVID-19 prescription, or identify sites that provide testing, medical care, and COVID-19 medications. 

Information provided in Yale Medicine articles is for general informational purposes only. No content in the articles should ever be used as a substitute for medical advice from your doctor or other qualified clinician. Always seek the individual advice of your health care provider with any questions you have regarding a medical condition.

New IDSA guidance covers drug interactions with Paxlovid

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The Infectious Diseases Society of America issued guidance to help clinicians manage drug interactions between Paxlovid and the 100 most prescribed medications.

Additionally, the FDA said there is no evidence to suggest that a longer course of Paxlovid will benefit patients who experience a rebound in COVID-19 symptoms after completing a 5-day course of the medication.

Source: Adobe Stock.
The IDSA issued clinician guidance for Paxlovid to minimize patient drug interactions. Source: Adobe Stock.

Pfizer received an emergency use authorization for Paxlovid — which consists of the protease inhibitor nirmatrelvir and a low dose of ritonavir — in late December, making it the first available oral antiviral for COVID-19. It has been shown to reduce the risk for hospitalization and death from COVID-19 by close to 90%.

The Biden administration announced last month that it was purchasing 20 million courses of Paxlovid, which is a focus of its test-to-treat initiative. The medication is now available at many U.S. pharmacies after an initial supply shortage, said Jason Gallagher, PharmD, a clinical professor at Temple University School of Pharmacy in Philadelphia.

Jason Gallagher

“Availability has improved considerably in the past few months, and it is much easier to access than many people think,” Gallagher told Healio. “Perceptions are not in line with the reality of the current supply.”

Reported cases of relapse following a 5-day course of Paxlovid for COVID-19 are mostly anecdotal, Gallagher said, “but that doesn’t mean they are not real.”

“The relapse rate in the study that led to its approval was similar between the Paxlovid and placebo groups — about 2% — but that was in an unvaccinated population with different variants,” he explained.

In a recent update for providers, the FDA said it was aware of reports of patients developing COVID-19 symptoms after completing a course of Paxlovid, including some who tested negative for SARS-CoV-2 and then positive again, but that there is “no evidence of benefit at this time for a longer course of treatment” — for example, 10 days instead of 5.

The FDA reanalyzed clinical trial data and said the reports “do not change the conclusions from the Paxlovid clinical trial, which demonstrated a marked reduction in hospitalization and death.”

“The only duration of therapy for Paxlovid that we have evidence to support is the 5-day course that received the EUA,” Gallagher said. “EUAs are specific, and prescribers do not have a choice but to follow it. There is no specific guidance, but FDA has said that if someone does relapse on Paxlovid there is nothing preventing a second course from being prescribed.”

In the event a second course is prescribed, the IDSA says the duration of therapy should be used to guide adjustments to concomitant medications.

Paxlovid is authorized to treat mild-to-moderate COVID-19 in patients aged 12 years or older who are at high risk for progression to severe disease and weigh at least 40 kg. IDSA guidelines state that Paxlovid should be initiated within 5 days of symptom onset. Additionally, the guidance says patients with mild-to-moderate COVID-19 who are at high risk for progression to severe disease and who are admitted to the hospital for something other than COVID-19 can also receive Paxlovid.

“That covers a lot of people,” he said. “People with diabetes, people who are obese, elderly people, immunocompromised people.”

He said the potential for drug interactions with Paxlovid may have “scared away” many prescribers. However, among the top 100 most prescribed drugs, the IDSA said only two have interactions so severe that Paxlovid should be avoided altogether: rivaroxaban and salmeterol.

“A few combinations rule out Paxlovid use, but most can be managed during the 5 days of therapy. There are other drugs that cannot be combined with Paxlovid, so each patient needs individual assessment done,” Gallagher said.

According to the IDSA guidance, clinicians should obtain a complete list of a patient’s current medications including over-the-counter agents and herbal supplements — confirming that the patient is taking each medication as prescribed. They should review the FDA Paxlovid health care provider fact sheet to identify any medications contraindicated with Paxlovid, review potential drug interactions between Paxlovid and the patient’s current medications, and advise patients of any dose adjustments.

References:

IDSA. Management of drug interactions with nirmatrelvir/ritonavir (Paxlovid): Resource for Clinicians. https://www.idsociety.org/paxlovid. Accessed on May 9, 2022.

Pfizer begins pediatric trial of COVID-19 antiviral

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Pfizer announced Wednesday that it has initiated a phase 2/3 study of its COVID-19 antiviral for pediatric patients.

Paxlovid, which contains tablets of the protease inhibitor nirmatrelvir and a low dose of ritonavir, is already available for patients aged 12 years or older under an emergency use authorization issued by the FDA in December.

Source: NIAID
Pfizer initiated a phase 2/3 study of its COVID-19 oral treatment Paxlovid for pediatric patients.

The new pediatric trial is an open-label, multicenter, single-arm study that will enroll approximately 140 participants aged younger than 18 years.

Initial enrollment will include two cohorts of participants aged 6 to 17 years. The first will include children weighing at least 40 kg, who will receive 300 mg of nirmatrelvir and 100 mg of ritonavir orally twice daily for 5 days — the currently authorized dose for patients aged 12 years and older weighing at least 40 kg. A second cohort of children weighing between 20 kg and 40 kg will also receive the therapy orally twice daily for 5 days, but with a reduced dose of nirmatrelvir (150 mg).

Mikael Dolsten, MD, PhD, Pfizer’s chief scientific officer and president for worldwide research, development and medical, said the antiviral may fill a “significant unmet need” for outpatient treatments for children and adolescents with COVID-19.

“Since the beginning of the pandemic, more than 11 million children under the age of 18 in the United States alone have tested positive for COVID-19, representing nearly 18% of reported cases and leading to more than 100,000 hospital admissions,” Dolsten said in a press release.

“Paxlovid is already authorized or approved in many countries around the world, with more than 1.5 million treatment courses delivered thus far and 30 million expected by July to help combat this devastating disease,” he said. “We are proud to expand studies of our novel COVID-19 treatment to include pediatric participants to further evaluate the safety and efficacy of this treatment in this important population.”

A final analysis of data from the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial demonstrated that Paxlovid reduced COVID-19-related hospitalizations and deaths by almost 90% among adults. The new trial is called EPIC-PEDS.

“Data from the EPIC-PEDS study will provide further support for the dose recommendations in this population, as well as potentially expand the indication to younger age groups and lower weights,” Pfizer said.