COVID-19 Treatment
Clarissa Chan, PharmD
Although pandemic restrictions around the United States are relaxing, CDC is still closely monitoring the SARS-CoV-2 virus Omicron variants, including BA.1, BA.1.1, and especially BA.2 lineages. Both NIH and IDSA recommendations, which have been updated recently, are continuously reviewed to provide important updates for pharmacists and other health care providers on the management and treatment of COVID-19.
“IDSA and NIH guidelines for outpatient management of mild to moderate COVID is something all retail and outpatient pharmacists should be aware of as the Biden Administration ‘test to treat’ initiative rolls out full steam,” said Raghav Tirupathi, MD, medical director at Keystone Infectious Diseases/HIV/Community Health Services and chair of Infection Prevention at Wellspan Chambersburg and Waynesboro Hospitals in Chambersburg, PA. “Pharmacists, being frontline in several communities, are in a unique position to check drug–drug interactions, counsel patients about oral therapeutic options including nirmatrelvir/ritonavir and molnupiravir, and direct them to the nearest monoclonal infusion resource if needed when patients are not candidates for oral treatments.”
The guidelines offer several options for at-risk outpatient populations.
“The priority order of which products should be utilized first and in which patient populations are extremely important,” said Christina M. Madison, PharmD, FCCP, AAHIVP, associate professor of pharmacy practice at Roseman University of Health Sciences College of Pharmacy in Las Vegas.
“Knowing the severity of illness classification [including asymptomatic or presymptomatic, mild, moderate, severe, and critically ill] is also important in choosing the right agent,” she said.
Currently authorized COVID-19 therapies
As of press time, NIH’s preferred therapeutic options for outpatient management (listed in order of preference) for treatment of mild to moderate disease in patients who are at high risk of progressing to severe COVID-19 include:
- Nirmatrelvir/Ritonavir (Paxlovid—Pfizer) given within 5 days of symptom onset
- Remdesivir within 7 days of symptom onset
Alternatives, if ineligible for the agents above, for treatment of mild to moderate disease include
- Betelovimab (12 years and older, weighing about 88 lbs and above) within 7 days of symptom onset
- Molnupiravir (18 years and older) within 5 days of symptom onset
Inpatient management therapies include remdesivir , tocilizumab, dexamethasone, and baricitinib.
Pre-exposure prophylaxis in immunocompromised patients
Tixagevimab/cilgavimab (EVUSHELD—AztraZeneca) is indicated for pre-exposure prophylaxis of immunocompromised people who are partially vaccinated, likely with inadequate immune response, or have contraindications or previous reactions or allergy to the vaccines.
“This is a dynamic recommendation due to the only FDA EUA PrEP monoclonal [antibody] EVUSHELD losing efficacy at standard dose after Omicron, which led to an increased dose of tixagevimab 300 mg and cilgavimab 300 mg administered as two separate consecutive intramuscular injections once,” said Tirupathi.
He is fearful that the new emerging BA.2 variant will make it completely ineffective.
“Although this therapy is currently in limited supply, its use is not being fully optimized. There needs to be a concerted effort to inform the public about this medication and its protective benefits,” said Madison.
NIH and IDSA guideline differences
“I prefer NIH guidelines as it is more granular and applicable to clinical practice,” said Tirupathi. “However, IDSA guidelines have considered more therapeutic options than NIH guidelines.”
The NIH guidelines are easier to read and digest; they have more charts, tables, and graphs and are better organized by groups of treatment types rather than listing all the information in chronological order of discovery, said Madison, who is also the founder and CEO of the Public Health Pharmacist, PLLC.
“I particularly like how Dr. Bhimraj and the team at IDSA have laid out the evidence-weighted recommendations per [Grading of Recommendations Assessment, Development, and Evaluation] protocol,” said Tirupathi.
There is also information regarding the possibility of co-infection for hospitalized patients—like those who have pneumonia, hepatitis B reactivation, and opportunistic fungal infections—addressed in the NIH guidelines. “This is particularly important for critical care pharmacists who may be managing these cases,” said Madison.
“There is some information that conflicts with NIH in the IDSA guidelines, specifically information about the use of therapies for post-exposure prophylaxis—which currently, due to Omicron [still] circulating, there are no [medications] that are recommended at this time,” Madison said.
“I tend to refer to both guidelines for answers,” Tirupathi said.
Current recommendations against use
“I am glad that both guidelines address the harm with [regard to] ivermectin and hydroxychloroquine. They also regularly update the evidence showing lack of efficacy as large trial data come in for ivermectin,” said Tirupathi. This helps providers dispel myths and address challenges regarding their choice to not prescribe medications for unapproved indications.
“However, fluvoxamine did have some promising data initially, but later large [randomized controlled] trials have not been convincing,” said Tirupathi. “There is more to come for this drug, which is recommended in WHO guidelines currently. Inhaled budesonide is another drug that continues to be evaluated.”
As of April 5, 2022, FDA rescinded authorization to treat COVID-19 with Sotrovimab in any U.S. region due to data showing that the authorized dose of Sotrovimab is likely to be ineffective against the currently dominant Omicron BA.2 subvariant.
No agents are currently authorized for post-exposure prophylaxis due to ineffectiveness against the Omicron variant. Bamlanivimab/etesevimab and casirivimab/imdevimab (Regen-CoV—Regeneron) were previously indicated but are not currently recommended because Omicron is the predominant strain.
The use of agents that have no proven efficacy and safety may be dangerous and destructive in the treatment and management of COVID-19. It distracts from the existing science and data of agents that have been proven both safe and effective, said Madison.
“More education regarding the potential harm and lack of benefit is needed in order to protect the health of the public,” Madison said.
Guideline improvement suggestions
Some recommendations in both guidelines are biased toward remdesivir in hypoxic hospitalized patients.
“Remdesivir has a role in early disease (as in PINETREE trial) and a limited role in hospitalized patients on low flow oxygen who had a mortality benefit in a subgroup analysis of the ACTT1 trial,” said Tirupathi. “Outside of these two situations, remdesivir is minimally effective in patients on high flow [nasal cannula, noninvasive ventilation,] or mechanical ventilation.”
While WHO guidelines have less emphasis on remdesivir, these guidelines may need to clarify the same more definitively to provide clarity to frontline providers, he said.
“Although not specifically addressed in the guidelines, who is eligible to prescribe and monitor these therapies is not defined. However, in a departure from normal course of practice, FDA specifically excludes pharmacist providers when authorizing the use of new oral antivirals nirmatrelvir/ritonavir and molnupiravir, which is an additional barrier to access to care that needs to be provided in a timely manner,” said Madison.
Public health impact
From a public health standpoint, the guidelines need to address issues around access, particularly in communities of color and disadvantaged areas that may be located in a “pharmacy desert,” said Madison.
“These medications require laboratory testing as well as observation time post infusion,” said Madison, regarding implementation best practices in order to overcome these barriers for patients who don’t have a medical home or primary care provider and lack access to medical care.
“Fortunately, there is not a lot of reported resistance to remdesivir or newer antivirals, but the monoclonal antibody treatment guidance changes every other week due to new variants,” said Tirupathi. ■