The Middletown Press (Middletown, CT)
Few people are taking CT’s more than 12K Paxlovid doses for COVID
Connecticut has many thousands of doses of free COVID antivirals available. But few patients are being prescribed the drugs.
Approved earlier this year under an emergency-use authorization, Pfizer's Paxlovid and Moderna's molnupiravir are the first outpatient therapeutics available to fight COVID, according to state Department of Public Health Commissioner Manisha Juthani.
“So far, all the treatments that we've had, and that have evolved over the last two years have been things that you need to be in the hospital to receive,” she said. “This is the first advance that we have, that is an oral medication, that people can go to a pharmacy and can pick it up.”
The medications, Juthani said, represent a shift in how the state is fighting the pandemic. While prevention remains critical, Juthani said
it's also important to keep hospitalizations down.
“The real impact is, how is it going to influence our health care delivery and our health care systems,” she said. “The endpoint of that is how many people are in the hospital.”
When they were first approved, the antivirals were difficult to obtain. More recently, federal officials have set up so-called test-to-treat sites where a patient can get tested for COVID and, if positive, be prescribed a therapeutic at the same location.
As of last week, federal authorities have sent 12,700 doses of Paxlovid and 20,612 doses of molnupiravir to Connecticut health care providers, including hospitals, pharmacies and urgent care centers. Paid for by the federal government, the drugs are free of charge to patients.
The problem is, few people are taking them. Doctors are hesitant to prescribe them, and patients, hearing about side effects, are reluctant to take them.
Both drugs are more effective if they're administered early in the course of the illness. Molnupiravir, Juthani said, has fewer drug interactions, but is less effective. Paxlovid is more effective, but has a significant number of interactions with other drugs.
This has made doctors, especially those in urgent care settings, reluctant to prescribe them.
The drugs are life-savers, according to Dr. Julian Nieves III, a practicing physician and assistant professor at the University of Connecticut's School of Medicine.
“It could be a life-saving therapy, especially with highrisk individuals,” he said, though he understands the reluctance. “Things are happening so fast that it does take a little bit of time for physicians and the public to become comfortable with any new therapeutic regimen.”
Shelton's Robert Wood, for example, began experiencing cold symptoms on Good Friday. A home test was positive and his doctor's office was closed, so he decided to get an antiviral at a local walk-in clinic.
“The walk-in did a PCR test that was positive,” Wood said. “The clinician said that she could not prescribe an antiviral, and if my symptoms worsened, I should go to a hospital ER. I did have symptoms and am 76 years old. The clinician handed me a sheet about the antiviral to educate me should I go to the ER.”
Wood said he “felt like the visit to the walk-in was a wasted trip.”
One doctor’s perspective
John Iannarone used to be in private practice, but he's semi-retired now, working part-time at an urgent care center.
When it comes to COVID antivirals like Pfizer's Paxlovid, the Monroe resident said he's “cautious” to prescribe them.
“Hesitant isn't the word. Just very cautious,” he said. “I think a lot of physicians are cautious, especially folks in the urgent-care setting.”
The issue, he said, is drug interactions. The antivirals tend to negatively interact with many drugs — 50 percent of commonly prescribed medications, by one estimation.
Doctors in walk-in clinics don't have previous relationships with their patients, and those in the throes of a COVID infection might not remember all of their prescribed medications.
“The interaction issue is the big deal,” he said. “The interaction list is immense.”
Another concern is side effects. While the vast majority of people tolerate the antivirals pretty well, there are a few who experience nausea and diarrhea.
Iannarone said he's heard of a few patients who, because of the “vomiting and the diarrhea, had to end up in the hospital for IV fluids because of the medicine.”
A doctor can't really anticipate which patient will experience significant side effects. Some just experience a bit of dry mouth.
“If you don't really know the patient, you certainly don't want the treatment to be worse than the disease,” Iannarone said.
All this hit home when his 95-year-old mother, Eleanore Iannarone, began to experience COVID symptoms.
“She had mild symptoms throughout, is feeling well now, just a little tired,” he said.
She's fully vaccinated and double-boosted, but her doctor son wanted to be safe, so after a positive home test, the Iannarones went to an urgent care.
In the end, the elder Iannarone did not take the antivirals.
“She is on medications, which would have interacted with Paxlovid, and of course, there was concern for nausea, vomiting and diarrhea side effects,” John Iannarone said. “My mom received IV monoclonal antibodies in the St. Vincent's ED.”
How Paxlovid works
Xiaobo Zhong, a professor of pharmacology and toxicology at UConn's School of Pharmacy, and three of his doctoral students — Roxanna Monshi, Julia Migliorati and Jing Jin — explained that Paxlovid is actually a combination of two things.
“Paxlovid has two components,” Jin said. “One is ritonavir and another one is nirmatrelvir.”
Nirmatrelvir is what actually fights the coronavirus. Ritonavir allows the body to better process the drug. The goal is for nirmatrelvir to reach the lung cells, where it fights viral replication.
But your liver gets in the way, metabolizing the nirmatrelvir and flushing it out of the system. That's where the ritonavir comes in. That drug is designed to “inhibit the metabolism of the liver” so the nirmatrelvir can “get into the lung cell to help prevent the virus infection,” Jin said.
But ritonavir affects an enzyme in the liver that many other drugs rely on, meaning, “basically people have a reduced capability to metabolize a lot of other drugs that commonly people use,” Zhong said.
If, for example, you are on a medication to keep your blood sugar down, the ritonavir can make it less effective.
Or, the opposite might happen. Some drugs “can decrease the efficacy of Paxlovid's antiviral activity by decreasing its blood serum concentrations,” Monshi said.
A doctor might suggest that you stop taking a drug during the five days while on Paxlovid. But Zhong said “some drugs you cannot stop.” Some drugs, “when you immediately stop, then they cause withdrawal syndrome, and they will make people also feel very sick.”
Migliorati advised that patients not only talk to their doctors, but speak with their pharmacists.
“There's healthy levels of skepticism. With many Americans on many different types of drugs, it can make prescribing very complex and it can most likely require a specialist in many cases,” she said. “So I understand that hesitancy.”
Sick, then sick again
Kate Gianelli, of Trumbull, got COVID, was prescribed Paxlovid, felt better and then started getting sick again.
“After feeling slightly better each day, I was exhausted all day Friday and just chalked it up to getting back into the groove, but took an antigen test Friday night,” she said. “I was shocked when my COVID line appeared before the solution had even reached the control line.”
Juthani said patients in Gianelli's case represent “a small subset of people whose symptoms go away. When they stop the medication, the symptoms come back.”
That reaction — getting a COVID relapse after the five-day antiviral course — was seen in the clinical trials, but wasn't initially published.
Juthani said it's one reason patients are reluctant to take the drug.
“There's some people I've heard say, ‘Well, if that's gonna happen, why bother taking it anyway?”
Gianelli, though, said she is glad for the prescription, even though her symptoms returned.
“I'm still turning tests positive immediately and have resumed isolation,” she said. “It's super frustrating, but I'm still glad I took Paxlovid.”
The value of education
Not all of the antivirals are being left on shelves.
“We're seeing that 55 percent of allocated Paxlovid to hospitals is getting used,” Juthani said.
The difference is comfort level. The drugs used in Paxlovid have been known to HIV specialists for decades, and Juthani said it will take time for the rest of the medical establishment to get comfortable.
“Some of it is people getting comfort and being like, ‘OK, I can prescribe this.' They get comfort with knowing how to do it,” she said.
The stories of side effects may be overstated. Zhong said the drug is “well tolerated,” and Juthani argued it's hard to know what's caused by the drug and what's caused by the virus.
“It's a balance, right? Because people are throwing up from COVID. That happens from COVID,” she said. “We don't know that it's the medication that's doing that, but people associate it that way. But we don't know that for sure, is that just the natural history of what was going to happen to you anyway?”
That's why, Juthani said, it's important for the state to educate doctors and patients about the risks and the benefits of COVID therapeutics. In the end, she said, it's a question of risk versus reward.
“I don't think people should prescribe things that they don't feel comfort prescribing, because their license is on the line, their name is on the line, and they should be entitled to say, ‘I'm not going to prescribe that because I don't feel comfortable doing that,'” Juthani said. “Now, what I would argue in this situation is, you can get comfort, you can get educated. That's what we're trying to do. We're trying to educate people. We're trying to show them it's not as scary.”