ASHP Midyear: Identify and Counsel Patients at High Risk for Severe COVID-19

Although managing COVID-19 has become largely routine, pharmacists should still be mindful when counseling patients at high risk of progressing to severe disease, defined as hospitalization or death. Importantly, counseling patients about the use of ritonavir and nirmatrelvir (Paxlovid; Pfizer) is a crucial role for pharmacists, according to a session at the American Society of Health-System Pharmacists Midyear 2024 meeting.¹

COVID-19 virus illustration | Image credit: © Production Perig | stock.adobe.com

Between April 2023 and April 2024, an estimated 61,000 total COVID-19–related deaths occurred in the United States, or about 2% of total deaths. Furthermore, an estimated 824,000 hospitalizations occurred as a result of COVID-19 illness, demonstrating the significant burden the virus continues to have.In addition to acute illness, presenter Jeff Brock, PharmD, MBA, BCIDP, highlighted the chronic conditions that are also associated with COVID-19, including hypertension, diabetes, mental health conditions, heart failure, kidney disease, and some thrombotic events.¹

New variants continue to emerge, increasing the likelihood of surges. As of May 2024, Brock said the most common variants (90.9% of cases) were KP and JN omicron subvariants. Emergent variants, particularly variants of interest such as omicron parent lineages, may be associated with increased transmission rates, reduced antibody neutralization, and diagnostic detection failures.¹

“It’s really important to understand these circulating variants and their impacts on our patients,” Brock said.¹

Symptoms of COVID-19 can include fever or chills, cough, dyspnea, fatigue, muscle aches, headache, sore throat, hoarse voice, congestion, nausea, and diarrhea. Emergency warning signs of more severe disease include trouble breathing; persistent chest pain or pressure; new mental confusion; inability to wake or stay awake; and discolored skin, lips, or nail beds. Illness persisting for more than a week also presents a greater risk for severe or critical illness. Brock emphasized that not only should pharmacists be aware of these symptoms, but they should educate patients so that they know when to seek medical care.¹

Although all patients should be aware of the common symptoms, identifying which patients are at the greatest risk is another role for pharmacists to play. The strongest risk factor is older age, defined as age 50 or older, and underlying medical conditions also heighten the risk.

“Often 65 years and up is…referred to as older age,” Brock said. “But with respect to COVID-19, anybody 50 years of age or older is included in the high-risk category.”

Some racial or ethnic minority groups are also considered at increased risk due to inequities in health care and socioeconomic factors. Additionally, individuals who are unvaccinated or not up to date on COVID-19 vaccines are at greater risk of severe outcomes. The CDC’s top 5 most common risk factors are hypertension, chronic pulmonary disease, obesity, metabolic disease, and cardiovascular disease.¹

Once patients have confirmed COVID-19, pharmacists should not only identify whether they are at heightened risk of severe disease, but should counsel them on treatment options, when appropriate. The use of ritonavir and nirmatrelvir can significantly lower patients’ risk of progressing to severe disease.¹

Nirmatrelvir is a peptidomimetic inhibitor of M^PRO1, which is a critical protein for viral replication and is highly conserved across coronaviruses. Ritonavir inhibits CYP3A-mediated metabolism of nirmatrelvir, resulting in increased plasma concentrations and enhanced therapeutic effect.¹ This treatment combination was used under Emergency Use Authorization during much of the COVID-19 pandemic, and was fully approved by the FDA in May 2023 for the treatment of mild-to-moderate COVID-19 in adults at high risk of progressing to severe disease.²

Paxlovid was investigated in the EPIC-HR randomized clinical trial, and has also undergone real-world evidence studies. The EPIC-HR study was a phase 2/3 randomized, double-blind, placebo-controlled trial in nonhospitalized symptomatic adults with confirmed SARS-CoV-2 and at least 1 high-risk factor for progression to severe disease. In total, 2113 participants were randomized (n=1049 Paxlovid) and the primary end point was proportion with COVID-19–related hospitalization or death from any cause through day 28.³

Participants were unvaccinated, 18 years of age or older, had confirmed SARS-CoV-2 infection, COVID-19 symptom onset within 5 days, and had 1 or more high-risk factor. Participants had a mean age of 45 years, 20.7% were 60 years or older, and 51% were male.³

“Paxlovid demonstrated powerful efficacy in this trial versus placebo,” Brock said. “Relative risk reduction for Paxlovid was 86% compared to placebo, reducing hospitalization or death from any cause through day 28.”¹

The most common adverse events (AEs) were altered taste and diarrhea. Notably, fewer patients discontinued treatment in the Paxlovid arm due to AEs than the placebo arm, highlighting its tolerability.³

Real-world evidence studies have further supported these findings. The study by Lewnard et al., funded by the CDC and National Institutes of Health, aimed to estimate the effectiveness of nirmatrelvir and ritonavir in preventing severe outcomes via a retrospective analysis within a large, integrated US health care system. Importantly, this study included vaccinated patients and data from the omicron era, unlike the EPIC-HR trial.⁴

Investigators used the Kaiser Permanente Southern California health care database of 4.7 million patients, with an analytic sample of 133,426 patients. According to the study, 24.6% of patients treated with ritonavir and nirmatrelvir were aged 50 or older, 42.3% were male, and 42.1% were Hispanic. Furthermore, 80.6% had received 3 or more previous doses of a COVID-19 vaccine.⁴

When receiving Paxlovid within 5 days of symptom onset, researchers found a 79.6% estimated effectiveness in prevention of hospitalization or death within 30 days. Furthermore, prevention of hospitalization or death for those with 3 or more prior vaccines was 92.2%, and was 83.1% for those with 2 or more previous doses.⁴

“The results from the Lewnard et al. study complimented those from the EPIC-HR study, but we should note that estimated effectiveness should not be compared between the different studies [due to differences in study design],” Brock said.¹

For patients eligible to receive Paxlovid, pharmacists should counsel them on the proper use of the medication. It is available in a standard dose (300 mg nirmatrelvir and 100 mg ritonavir) and a reduced dose (150 nirmatrelvir, 100 mg ritonavir) for those with severe kidney impairment. Brock noted that individuals with mild or moderate kidney impairment and individuals with mild or moderate hepatic impairment can receive the standard dose, although those with severe hepatic impairment should not receive Paxlovid.¹

Patients should be counseled that it can be taken with or without food. If the patient misses a dose by less than 8 hours, they should take the missed dose as soon as possible and resume the normal schedule. If the dose is missed by more than 8 hours, they should skip the missed dose and take the next one as scheduled.¹

Pharmacists play a critical role in ensuring the safe and effective use of ritonavir and nirmatrelvir. Their expertise in medication therapy management, drug-drug interactions, and patient counseling is invaluable in guiding patients through the treatment process. By identifying patients at high risk for progressing to severe disease and counseling them on their treatment options, pharmacists empower patients to make informed decisions about their treatment.

REFERENCES

1. Brock J. Clinical Trial Data and Real-World Evidence Behind an Oral Treatment Option for Adult Patients at High Risk for Progression to Severe COVID-19. Presented at: American Society of Health-System Pharmacists Midyear 2024 meeting. New Orleans; LA. December 8, 2024.

2. FDA Approves First Oral Antiviral for Treatment of COVID-19 in Adults. News release. FDA. May 25, 2023. Accessed December 8, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-antiviral-treatment-covid-19-adults

3. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. N Engl J Med. 2022;386(15):1397-1408. doi:10.1056/NEJMoa2118542

4. Lewnard JA, McLaughlin JM, Malden D, et al. Effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system. Lancet Infect Dis. 2023;23(7):806-815. doi:10.1016/S1473-3099(23)00118-4