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Prescribing Paxlovid, the oral COVID-19 outpatient treatment recommended by the National Institutes of Health (NIH), has underscored the importance of strong clinician–pharmacist relationships and of communication with patients, residents, and their families and caregivers about medication safety and drug-drug interactions.
“We’ve had very thorough conversations [with families] up front about adjustments [in other medications] that need to be made, and about the risks of medication interactions. And, of course, we talk about the fact that the medication is still under [emergency use authorization],” said Holly W. Wenger, AGNP-C, who practices at The Forest at Duke, a continuing care retirement community in Durham, NC. The U.S. Food and Drug Administration issued the emergency use authorization (EUA) in December 2021.
In her experience, most patients and families can make a decision about Paxlovid after an initial conversation, at least partly because “they’re most concerned about the prevention of severe illness and long COVID,” Ms. Wenger said, noting that with long COVID there have been no prevention data to share.
Paxlovid is composed of nirmatrelvir, a SARS-CoV-2 main protease inhibitor, co-packaged with ritonavir, an HIV-1 protease inhibitor. Ritonavir is a potent CYP3A inhibitor, which leads to a long list of clinically significant drug-drug interactions. There are additional contraindications and clinical considerations (e.g., renal dosing). Some experts have expressed concern over the limitations of the research supporting the EUA, which was conducted during the Delta variant surge in 2021 and included only unvaccinated individuals.
However, Swati Gaur, MD, MBA, CMD, is among the many who say that its recommended use in older adults is solid. “There’s compelling data that Paxlovid is beneficial in people who have that higher risk of deterioration,” and most of her long-term care residents who’ve become infected have been eligible for its use, she said.
Antiviral treatment layered on top of high vaccination rates is key to making the “huge strategic change from a deadly infection into a milder viral infection that may become endemic in our community,” said Dr. Gaur, medical director of Georgia-based Horizons Lanier Park and New Horizons Limestone facilities.
The primary data for the EUA came from the Pfizer-sponsored EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) study, a randomized, double-blind, placebo-controlled phase 2-3 study of over 2,000 patients at high risk for progression to severe disease. Investigators found an 89.1% relative risk reduction in COVID-19–related hospitalization or death from any cause by day 28 (N Engl J Med 2022;386:1397–1408).
In August 2022, an Israeli study including over 42,000 patients aged 65 and older found relative risk reductions in this age group of 73% for hospitalization and 79% for death for patients receiving Paxlovid. (No evidence of benefit was found in younger adults.) The study was one of the first looks at Paxlovid’s effectiveness against the Omicron variant (N Engl J Med 2022;387:790–798).
Drugs that may interact with Paxlovid include medications commonly used to manage cardiovascular conditions. A recent review of known and potential interactions with cardiovascular drugs published in the Journal of the American College of Cardiology concludes that the importance of medication reconciliation before initiation of Paxlovid “cannot be overemphasized to avoid serious DDIs” (Epublished DOI: 10.1016/j.jacc.2022.08.800).
In Dr. Wenger’s population, antiarrhythmic agents such as amiodarone have been the biggest barrier to prescribing Paxlovid. Otherwise, “we’ve collaborated with the pharmacists quite a bit on holding medications or adjusting dosages,” she said.
Statins are “one of the common offenders” in the geriatric population, but the recommended five-day hold during Paxlovid treatment for many statin recipients (i.e., those receiving atorvastatin or rosuvastatin) is usually not problematic, said Nicole J. Brandt, PharmD, MBA, BCGP, BCPP, FASCP, executive director of the Peter Lamy Center on Drug Therapy and Aging and professor of pharmacy practice and science at the University of Maryland School of Pharmacy.
Lovastatin and simvastatin need to be held for longer, from 12 hours before the first dose of Paxlovid through five days after the COVID treatment.
Dose reductions of certain high-risk medications such as anticoagulants and digoxin are more challenging in the decision-making process, Dr. Brandt said, recalling a case in which a family decided not to use Paxlovid in the face of needed reductions of apixaban and digoxin and additional monitoring.
“Reductions in [direct oral anticoagulants] can be concerning, especially for patients at high risk of having a stroke or [deep vein thrombosis] and given what we know about the virus being thrombotic and causing increases in inflammatory markers,” said Dr. Brandt.
Pharmacists both inside and outside long-term care have put in place processes and order forms using EUA information to screen patients for drug interactions, severe renal and hepatic impairment, symptom onset, and other factors, she said, noting that Paxlovid can be crushed.
Clinicians have as well. Dr. Gaur said her facilities use a screening checklist tool for prescribers offered by the FDA. When the drug became available, they also implemented standing orders for a complete blood count and comprehensive metabolic panel to automatically assess liver and renal function whenever a resident tested positive for SARS-CoV-2.
Per the EUA, the medication is not recommended in cases of severe hepatic impairment (Child-Pugh class C), but may be used without any dose adjustment in patients with mild or moderate impairment (classes A and B). Dr. Gaur said that personally would lean toward alternatives in patients who have any liver abnormalities.
(The NIH guidelines recommend Remdesivir as a second-line choice and bebtelovimab and molnupiravir as alternative therapies when Paxlovid and Remdesivir aren’t options.)
For patients with moderate renal impairment (estimated glomerular filtration rate of ≥30-<60 mL/min/1.73 m2), reduced doses of Paxlovid are packaged and have been commonly used in long-term care, Ms. Wenger said. (Known or suspected severe renal impairment is a contraindication.)
Preparedness is key, Dr. Gaur said. “We don’t have the luxury of leisurely adopting these treatments,” she said. “And if we have an outbreak, we need to anticipate more cases and ask, What are the therapeutics in stock? What are the logistics for securing them?”
Most skilled nursing facilities have been receiving the government-procured Paxlovid through their state or jurisdiction’s health department, though some long-term care pharmacies serving nursing homes have been receiving it directly from the federal government as part of its Federal Retail Pharmacy Therapeutics Program, according to a Department of Health and Human Services spokesperson.
However, the federal government has indicated that coverage and distribution of Paxlovid will transition to the commercial market in mid-2023 (D. O’Connell, “COVID-19 Medical Countermeasures and the Commercial Marketplace,” ASPR Blog, Aug. 30, 2022, https://bit.ly/3S7Nxt4). Bebtelovimab was transitioned in August 2022, and molnupiravir is expected to transition in the first or second quarter of 2023, before Paxlovid.
Side Effects, Meaningful Conversations
In their experiences and communities, sources said, the most common side effect has been a metallic sense of taste and occasionally some diarrhea and/or nausea.
Ms. Wenger, Dr. Gaur, and Dr. Brandt each said they had not encountered much COVID-19 rebound after Paxlovid use. Ms. Wenger said she has wondered about missing rebound COVID symptoms — and possibly side-effect symptoms — in residents with dementia due to their communication deficits.
The new year should bring more guidance on several fronts. The FDA asked Pfizer in August to conduct a randomized placebo-controlled trial evaluating a second five-day treatment course in patients with rebound, with results reported by September 2023. It also asked for a safety and pharmacokinetic study of Paxlovid in patients with severe renal impairment, with results by the end of February 2023.
In the meantime, COVID-19 remains a moving target, and some experts have expressed concerns that infections with new variants may not be as responsive to available treatments.
As long as Paxlovid measures up, individualized decision-making — and conversations — will be key. A caregiver and husband to a resident of a nursing home in Catonsville, MD, told Caring that he agreed to Paxlovid during a quick phone call but then developed questions.
It all worked out: his wife left isolation and has not experienced any of the known side effects — and his questions were answered through conversations with a pharmacist, a former colleague, and another friend.
“But I did everything in reverse. What I really needed was time to get information and make an informed decision ... for the professional caregiver to say ‘we want to put your wife on Paxlovid, and let’s take 10 minutes so I can explain it all to you,’” he said.
Christine Kilgore is a freelance writer based in Falls Church, VA.
In addition to EUA information, sources suggested these resources:
In this episode, Dr. Karl Steinberg and Dr. Elizabeth Galik discuss our November-December issue, including the oral COVID-19 outpatient treatment known as Paxlovid, the role of professional social workers in the nursing home, the assessment and management of wandering and elopement in nursing homes, and what to do with spousal disagreements impact individuals, other patients, and staff.