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Is the Oral Pill Paxlovid an Answer to COVID-19?

What should you know about PAXLOVID, an oral medicine against COVID-19? How hard is it to get an Rx? What about dangerous interactions?
Is the Oral Pill Paxlovid an Answer to COVID-19?
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The FDA has granted Emergency Use Authorization (EUA) for the oral antiviral drugs Paxlovid (nirmatrelvir + ritonavir) and Legevrio (molnupiravir) to treat COVID-19. Even though that happened about a month ago, finding Paxlovid pills is challenging. Many pharmacies have inadequate supplies. And many doctors won’t prescribe it without actually seeing patients in person, even if they report a positive home test. And it can take a lot longer than three days to get an appointment with the prescriber. The drug works best if it is taken within a short time after developing symptoms.

How Effective is Paxlovid?

According to Pfizer, the drug:

“…showed an 89% reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset; 0.8% of patients who received PAXLOVID™ were hospitalized through Day 28 following randomization (3/389 hospitalized with no deaths), compared to 7.0% of patients who received placebo and were hospitalized or died (27/385 hospitalized with 7 subsequent deaths). Similar reductions in COVID-19-related hospitalization or death were observed in patients treated within five days of symptom onset; 1.0% of patients who received PAXLOVID™ were hospitalized through Day 28 following randomization (6/607 hospitalized, with no deaths), compared to 6.7% of patients who received a placebo (41/612 hospitalized with 10 subsequent deaths).”

Please keep in mind that this is an “interim analysis.” We will need to see the final analysis to know if these numbers hold up.

How Does Paxlovid Work?

This oral medication works differently from molnupiravir. Paxlovid attacks protease enzymes that are essential for snipping strands of viral protein. In this way the drug blocks replication of COVID-19.

Molnupiravir works by forcing the virus to scramble its genetic code. By inducing mistakes, the drug forces the virus to mutate. As a result, it can no longer reproduce. Both drugs interfere with the ability of SARS-CoV02 to replicate. They just use different mechanisms.

Paxlovid vs. Molnupiravir:

At first glance, Paxlovid appears to be the hands down winner in the battle of the oral antiviral meds against COVID-19. The interim analysis suggests 89% effectiveness vs. 30% effectiveness for molnupiravir. That’s relative risk reduction.

Let’s compare absolute risk reduction. In the molnupiravir trial 68 out of 699 placebo patients were hospitalized or died (9.7%). The active drug reduced hospitalization or death to 48 out of 708 (6.8%). That is a 3% absolute risk reduction with molnupiravir.

In the Paxlovid trial, 27 out of 385 patients receiving placebo were hospitalized or died (7%). The active drug reduced that to 3 people hospitalized out of 385  (0.8%). That is a 6% absolute risk reduction with the Pfizer drug. Paxlovid seems to be winning big, but there are some disadvantages too.

The Downside of Paxlovid:

Patients will need to take the Pfizer pill with another medication, an HIV/AIDS drug called ritonavir (Norvir). This second pill interferes with the body’s ability to break down (metabolize) Paxlovid. As a result, ritonavir prolongs the activity of the anti-COVID drug.

We don’t know a lot about Paxlovid’s side effect profile. But we do know that ritonavir can cause digestive tract upset (nausea, vomiting, stomach pain, diarrhea), fatigue, cough, dizziness, itching, confusion and fluid retention. That’s just for starters. There are many other potential adverse reactions. Fortunately, the dose of ritonavir is considered low and it is taken for only five days.

Dangerous Drug Interactions:

The real challenge with ritonavir has to do with drug interactions. This medication can interact with hundreds of other drugs. That means doctors will need to be extremely careful if they consider prescribing the Paxlovid/ritonavir combination to patients who are taking any other meds.

For example, ritonavir should not be prescribed to patients taking drugs such as atorvastatin, amiodarone, butalbital, carbamazepine, dronedarone, eletriptan, enzalutamide, lovastatin, metronidazole, midazolam, modafinil, phenobarbital, phenytoin, sildenafil, sirolimus, tacrolimus or triazolam.

That too is just for starters. There are literally hundreds of other drugs that make Pfizer’s antiviral combo problematic. People taking drugs to control cardiac arrhythmias, high blood pressure, elevated cholesterol and HIV infections may have serious complications as a result of drug interactions. Anyone prescribed Paxlovid must ask both the physician and pharmacist to review all other drugs they take to prevent dangerous interactions.

COVID Resistance?

There is one other potential complication. In our conversation with Dr. Ralph Baric about oral antiviral drugs against COVID-19, he raised the possibility that the SARS virus could develop resistance to the antiviral medicine. You can listen to our interview with him in which he discusses the oral meds and the likely future of the COVID pandemic. Here is a link to the podcast:

Show 1281: New Antiviral Pills and the Future of COVID-19
Coronavirus hunter Dr. Ralph Baric helps you understand the future of COVID-19. How can we become better prepared for the next pandemic?

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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