Case Study: Barbara is a 64-year-old woman who tested positive for COVID-19 from exposure she believes occurred on Saturday night after attending a social function. On Monday she is feeling lethargic and by Tuesday night she has developed a low-grade fever and a dry hacking cough. She is fully vaccinated with an mRNA vaccine and received one booster in the fall of 2021. She seeks your advice on Wednesday morning at the pharmacy drive-up window. Should she talk to her primary care provider about an antiviral medication? Is she a candidate? How well do these medicines help to prevent a more serious course and—a primary concern for her—to prevent post-COVID syndrome, also known as “long COVID”? Barbara also asks whether you, the pharmacist, can arrange for her to get a prescription. The window of efficacy for these medications is brief and access to urgent care is limited in her rural area. What can pharmacists tell a patient like Barbara, whose age places her on the margin of the Centers for Disease Control and Prevention (CDC) priority group? In addition, how can pharmacists advise other patients who are more clear-cut candidates for prevention of severe COVID?

There is a critical and urgent need for effective targeted treatments for COVID-19 infection, and an equally critical need for information and support for healthcare professionals providing patient care during this ongoing global crisis. Pharmacists have expanded their practices to care for patients with COVID-19 during these unprecedented times.^{1, 2} As of July 2022 pharmacists were authorized by the Food & Drug Administration (FDA) to directly prescribe one of the oral COVID-19 antiviral agents under certain conditions (see Sidebar 1).³ In addition, pharmacists are actively involved in medication distribution and administration, adverse effect management, drug interaction assessment and intervention, patient education, and vaccination practices.

COVID-19 variants continue to be a fast-moving target. Keeping up with rapidly evolving changes in COVID-19 management presents a significant challenge to pharmacists. As newer antiviral therapies have been introduced into the COVID-19 armamentarium, others, such as a number of monoclonal antibody therapies, have been waylaid due to the influence of viral variants like Omicron BA.2, BA.2.12.1, BA.4, and BA.5. Pharmacists need accurate and up-to-date information to fulfill their role of integrating antiviral therapies into clinical practice.

Patient Selection Criteria for Outpatient Antiviral Treatment

A particular focus of research into COVID-19 interventions is protecting individuals who are at highest risk for severe complications from the infection. Some of these persons remain unvaccinated for in rare cases medical or more commonly personal reasons—although the benefits of vaccination are generally recommended by the CDC as outweighing the risks.⁴ Others may mount an inadequate response to the vaccine.⁵ People with certain immunocompromising conditions remain at substantial risk for infection, severe illness, and death, especially at times when the level of SARS-CoV-2 community transmission is high.⁵ According to interim guidance from the CDC, these populations include:⁴

• Patients receiving chemotherapy for cancer
• Patients with hematologic cancers (e.g., chronic lymphocytic leukemia)
• Recipients of stem cell or solid organ transplants
• Patients undergoing hemodialysis
• People taking certain medications that may blunt immune response to vaccination. These include but are not limited to, mycophenolate, rituximab and other anti-CD20 monoclonal antibodies, azathioprine, and Bruton tyrosine kinase inhibitors⁶

The NIH Treatment Guidelines categorize patient groups into tiers based on their prioritization for antiviral therapy (Table 1).⁷ These tiers were particularly relevant initially, when antiviral medications for COVID-19 were in very short supply. As the drugs have become more widely available, the selection criteria may be applied somewhat more loosely, especially for older adults.⁸ Increasing demand for the treatment may be anticipated among younger and healthier individuals who want to reduce their risk of spreading an infection to others or potentially sustaining long-term consequences (e.g. long COVID) even after a relatively mild course of illness. Data supporting a decreased risk of long COVID with antiviral therapy is currently not available.

What Are the Latest Developments in Outpatient COVID-19 Antiviral Therapy?

Better treatments for active cases of COVID-19 are critical to protect vulnerable patients and to reduce the impact of the infection for all individuals, including healthcare providers. Any treatments that can be shown to reliably decrease the severity or shorten the span of the illness—or reduce the risk or impact of a new infection—are enormously welcomed in the healthcare setting and to speed return of normal life and economic recovery. Some monoclonal antibody-based therapies and combinations have been introduced that offer greatly reduced morbidity and mortality from COVID-19.^{9, 10} Because of mutations in SARS-CoV-2 with the currently circulating Omicron variant, the only monoclonal antibody that remains effective is bebtelovimab.¹⁰ In addition, oral therapies that allow easier and more economic distribution and administration could have a dramatic effect on the pandemic in the U.S. and worldwide.¹¹ As of June 15, 2022, two oral antiviral therapies are authorized for emergency use. Others may follow in this rapidly changing field.

Antiviral Therapies for Outpatient Treatment of COVID-19

The quest for emergency authorization of oral antiviral drugs to treat COVID-19 has moved rapidly forward in recent months. In mid-November 2021, a request for emergency use authorization (EUA) was submitted for an oral antiviral COVID-19 treatment (Paxlovid®) combining the experimental protease inhibitor nirmatrelvir (PF-07321332) plus ritonavir as a booster.¹² Nirmatrelvir is a SARS-CoV-2 main protease inhibitor, while ritonavir is an HIV-1 protease inhibitor as well as a CYP3A inhibitor.¹³ Nirmatrelvir inhibits viral replication at the proteolysis stage, before viral RNA replication, while low-dose ritonavir helps to slow the metabolism of nirmatrelvir so it can remain active in the body for longer periods of time at higher concentrations. The FDA authorization was based on preliminary data from the Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) interim analysis.¹⁴ This trial enrolled unvaccinated non-hospitalized adults with confirmed COVID-19 who are at increased risk of progressing to severe illness. Compared with placebo, treatment with the protease inhibitor combination resulted in an 89% reduction in the risk of COVID-19-related hospitalization or death from any cause among patients treated within three days of symptom onset. These benefits were confirmed in patients who were treated within 5 days of symptom onset. There were no deaths in the treatment group. Treatment-emergent adverse events were comparable in both groups and most events were mild.

While the data are yet to be published in a peer reviewed format, the manufacturer of Paxlovid noted in a press release dated June 14, 2022 that it would cease enrollment in the EPIC-SR study due to futility.⁶ The EPIC-SR study was evaluating Paxlovid in standard-risk patients with the endpoint of self-reported, sustained alleviation of all symptoms for four consecutive days. There were low hospitalization rates in both the treatment and placebo arms, which contained both vaccinated and unvaccinated patients.⁶ Further studies will include the use of Paxlovid in patients who are vaccinated and had a breakthrough infection and for post-exposure prophylaxis in household contacts of people with positive tests for SARS-CoV-2 with or without symptoms.⁶

Molnupiravir (Lagevrio®) is an investigational, oral form of a ribonucleoside analog that inhibits replication of the SARS-CoV-2 virus.¹¹ The treatment was studied in MOVe-OUT, a Phase 2/3 randomized trial among non-hospitalized adults with mild to moderate laboratory-confirmed COVID-19. Trial participants were unvaccinated and had at least one risk factor associated with poor disease outcomes (e.g., older age, diabetes, obesity).¹⁵ Preliminary findings from MOVe-OUT among 1433 participants (716 treated; 717 placebo) showed that treatment with the antiviral agent reduced the risk of hospitalization by nearly 50% versus placebo (7.3% vs. 14.1%) at day 29. At final analysis, molnupiravir reduced the risk of hospitalization by approximately 30% versus placebo (6.8% vs. 9.7%) at day 29. Adverse events were comparable across all groups. In the preliminary analysis there were 9 deaths in the placebo group and 1 death in the active therapy group. Molnupiravir is also being studied for use as a post-exposure prophylactic agent among household contacts in the MOVe-AHEAD study.^{16, 17} Emergency Use Authorization (EUA) was approved for molnupiravir in the U.S. on December 23, 2021. Emergency approval was also issued in Europe on November 4.¹⁸

The NIH currently ranks ritonavir-boosted nirmatrelvir (Paxlovid) as the first choice for eligible outpatients with COVID, followed by remdesivir (Veklury®). The monoclonal agent bebtelovimab and the oral agent molnupiravir (Lagevrio®) are listed as alternative therapies for use when the first two therapies are unavailable or not clinically appropriate (see Figure 1 in the NIH COVID-19 treatment guidelines).⁷

Injectable and Infused Antiviral Agents for Outpatient Treatment of COVID

Remdesivir is a SARS-CoV-2 nucleotide analog RNA polymerase inhibitor approved for use in adults and pediatric patients (≥28 days of age and weighing at least 3 kg) who are hospitalized, as well as those not hospitalized with milder disease who are at high risk for progression to severe COVID-19. In a study of unvaccinated outpatients with COVID, this agent reduced the risk of hospitalization and death by 87%.¹⁹ For most outpatients (adults and children weighing at least 40 kg) remdesivir is given via intravenous (IV) infusion as a single 200-mg loading dose on Day 1 followed by 100-mg once daily on Days 2 and 3.²⁰ For non-hospitalized patients the treatment course should be initiated as soon as possible after diagnosis and within 7 days of symptom onset. Recommendations for durations of therapy differ for hospitalized patients. Remdesivir is not recommended in patients with eGFR less than 30 mL per minute due to a renally cleared excipient, betadex sulfobutyl ether sodium (SBECD), that can accumulate in this population.²⁰

While not an antiviral agent, the monoclonal antibody bebtelovimab is listed by the CDC along with molnupiravir as “alternative agents” for use in outpatients at risk of severe illness from COVID-19.²¹ Like other monoclonal antibodies directed against this virus, bebtelovimab binds to the SARS-CoV-2 spike protein, preventing viral entry into host cells.²² Bebtelovimab is notable in that the epitope to which it binds appears to mutate infrequently, potentially extending this drug’s viability in the face of resistant strains including the current Omicron variants. The drug is administered as a single intravenous (IV) injection over approximately 30 seconds.²³ Clinical trial data informing guideline recommendations to date is limited to a single phase II trial in patients who were at low risk of severe disease progression. More data are needed to better ascertain bebtelovimab’s role long-term, especially in patients at high risk for progression to severe disease.

Dosage, Interactions/Contraindications

Dosage schedules, adverse effects, and monitoring recommendations for outpatient antiviral therapies and bebtelovimab are summarized in Table 2.^{13, 18, 20, 23}

Nirmatrelvir plus ritonavir dosing

Nirmatrelvir plus ritonavir (Paxlovid) is indicated for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adult and pediatric patients (≥12 years and weighing at least 40 kg) who have tested positive for SARS-CoV-2 and who are at high risk for progression to severe COVID-19, including hospitalization or death.¹³ Each dose contains 300 mg nirmatrelvir (two 150 mg tablets) and 100 mg ritonavir (one 100 mg tablet). The three tablets are taken together, with or without food, twice daily for 5 days.

Paxlovid is not recommended for use in patients with severe renal impairment, defined as estimated glomerular filtration rate (eGFR) <30 mL/min), or for patients with severe hepatic impairment (Child-Pugh Class C). For patients with moderate renal impairment (eGFR between 30 mL/min and 60 mL/min), a dosage reduction is recommended of 150 mg nirmatrelvir (one 150 mg tablet) plus 100 mg ritonavir (one 100 mg tablet), with both tablets taken together twice daily for 5 days.¹³

Nirmatrelvir plus ritonavir interactions

Because ritonavir is a potent inhibitor of CYP3A, Paxlovid is involved in a number of potentially significant drug interactions. Per the FDA Fact Sheet for this product, Paxlovid is contraindicated in patients who are taking medications that are highly dependent on CYP3A for clearance. Administration of medications that are metabolized by CYP3A in patients already receiving PAXLOVID may increase the plasma concentrations of medications metabolized by CYP3A. Selected agents are summarized in Table 3.¹³ For the full list of drug-drug interactions for this therapy please consult the FDA Fact Sheet for Emergency Use Authorization of Paxlovid.¹³ (https://www.fda.gov/media/155050/download).

Paxlovid contraindications also include concomitant use with drugs that are potent CYP3A inducers that might significantly reduce the efficacy of either ingredient (nirmatrelvir or ritonavir) due to lowered plasma concentrations (Table 4). Paxlovid cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer.¹³

Other excellent resources, in addition to the package labeling, are available free to pharmacists when evaluating potential drug-drug interactions of Paxlovid. The NIH COVID-19 Treatment Guidelines has a recently added section specific to evaluating potential Paxlovid interactions.²⁴ Drug therapies that may have an interaction when given with Paxlovid are classified into categories including: 1) Prescribe alternative COVID-19 therapy; 2) Temporarily withhold concomitant medication, if clinically appropriate; 3) Adjust concomitant medication dose and monitor for adverse effects; and 4) Continue concomitant medication and monitor for adverse effects. The University of Liverpool also provides a detailed drug interaction checker with an in-depth analysis of any potential interaction and recommendations for decision-making.²⁵ When evaluating potential drug interactions of Paxlovid, it would be prudent for pharmacists to utilize these resources to make an informed decision.

Molnupiravir

Molnupiravir is supplied as a 200-mg oral capsule. The dosage is 800 mg (taken as 4 capsules by mouth with or without food) every 12 hours, for 5 days. Molnupiravir is authorized only for patients 18 years and older because of the potential risk of inhibiting bone and cartilage growth.¹⁸ While no specific contraindications are listed in the FDA emergency authorization fact sheet, this treatment is not recommended in patients who are pregnant (or might become pregnant) or breastfeeding due to the lack of data. Men of reproductive potential should be counseled to abstain from heterosexual sex or use contraceptives during therapy and for 3 months thereafter.¹⁸ In addition, no drug interactions have been identified based on the available data. While the safety profile of this agent is favorable relative to the authorized oral antiviral combination, the lower efficacy results limit the use of this agent to a subset of patients who cannot take the other agents.²⁶ Optimal candidates might include patients who have a documented allergy/intolerance to an ingredient in Paxlovid, those who are taking a medication that is absolutely contraindicated with Paxlovid therapy, or those who logistically cannot receive intravenous remdesivir therapy in a timely manner and where oral molnupiravir may be preferred. In addition, depending on supply chain constraints, if Paxlovid and remdesivir were not available locally then molnupiravir could be a feasible treatment option.

Case Study (continued): You are in a position to counsel Barbara, a 64-year-old SARS-CoV-2–positive patient, about whether she can benefit from an antiviral therapy. Based on the timing of the onset of her symptoms, she is within the appropriate window of time to benefit from antiviral treatment. The remaining questions, based on a combination of CDC recommendations, might include:

• Does Barbara have a comorbid condition that would warrant a prescription due to potential high risk of severe COVID-19 illness?
• Does this patient have any contraindications to Paxlovid therapy?
• Does the patient’s medication history allow for concomitant Paxlovid therapy? If so is a dose/frequency modification recommended?
• What steps should Barbara follow to obtain a prescription if she is a candidate for treatment?

For the first question, one should consider the age of the patient. CDC recommendations specify that patients receiving antiviral therapies must be 18 years or older. The latest CDC interim recommendations state that “age is the most important risk factor for severe outcomes of COVID-19.”²¹ Based on the evidence of COVID-19 risk in older adults, advanced age could warrant antiviral treatment in this case.

Asked if she has any conditions associated with severe illness from COVID-19, Barbara mentions she is currently taking adalimumab therapy for her Crohn’s disease and also has asthma for which she takes an inhaled corticosteroid. Antiviral therapies against COVID-19 are effective in a number of different patient populations but data regarding outcomes in fully vaccinated with or without booster therapy are limited. Due to her age and immunosuppressive therapy as well as asthma, initiation of antiviral therapy is indicated as the benefit likely outweighs the risk. A subgroup analysis of the previously mentioned EPIC-SR study failed to show benefit for vaccinated Paxlovid-treated patients at standard risk who had at least one risk factor for severe COVID-19, but this patient has several risk factors that place her in the higher risk category.⁶ Many patients report a rapid reduction of symptoms soon after beginning the course of treatment. You recommend that she seek either an immediate telemedicine visit with her primary care provider or an appointment at a local urgent care center.

The patient confirms that contraindications to therapy are not present (e.g., allergy or intolerance to Paxlovid components including ritonavir).

You advise the patient to have a list of all her medications to discuss with the provider and assist her in preparing the list. Her medications are lisinopril 40mg PO daily, adalimumab 40mg subcutaneously q 2 weeks, fluticasone HFA 220mcg inhaled twice daily, chlorthalidone 25mg PO daily, omeprazole 20mg once daily, and levothyroxine 100mcg PO daily. Considerations for therapeutic selection include availability of chosen therapy, preferred route of administration (oral vs. intravenous), potential for drug interactions, pregnancy or lactation status, and baseline renal and hepatic function. You advise the patient to discuss this with her provider and encourage her to take notes about the information she receives.

As a final step, you confirm that the pharmacy has doses of the antiviral medication for pickup if Barbara obtains a prescription. She should be advised about appropriate infection control precautions if she plans to pick up the medication herself. Once a medication is selected, the pharmacy staff can provide assistance with dosage instructions as well as expectations regarding efficacy and the most common side effects. In addition, because a few patients receiving Paxlovid therapy have reported rebound symptoms after completing therapy, counseling about this possibility is warranted.²⁷ In a recently published cohort, rebound occurred in fewer than 1% of patients, onset of rebound symptoms occurred at a median of 9 days after completion of Paxlovid therapy, and no patients required retreatment. Symptoms usually resolve within 3 days without treatment.²⁸

Role of Pharmacists in Distributing Antiviral Agents

During the pandemic, pharmacists have been involved in assisting with drug shortages and strategies for drug conservation, participating in emergency care, creating evidence-based guidelines, and developing protocols to integrate these recommendations into clinical practice.²⁹ These responsibilities are in addition to the immense and ongoing COVID-19 vaccination workload for pharmacists including new populations who are eligible for booster doses. It is also important for pharmacists to be aware of ongoing research into antiviral therapies and other interventions that reduce the risk of further viral transmission and serious illness, hospitalization, and death.

Pharmacists can serve important roles in the distribution and administration of oral antiviral therapies. Unlike monoclonal antibodies that require professional administration, these treatments are likely to be game-changers since they can be distributed in urgent care clinics and directly through pharmacies in some cases. With many pharmacies already performing COVID-19 testing and vaccination, pharmacists could serve as essential care points to not only identify patients who are candidates for oral therapy to prevent serious illness but to follow through with the Test to Treat Initiative now underway.³⁰ Authorization for pharmacists to prescribe these agents directly has been pursued by multiple pharmacy organizations through engagement with the federal government (see Sidebar 2).^{30, 31}

As of July 6, 2022, the FDA issued an authorization for state-licensed pharmacists to directly prescribe Paxlovid under certain conditions.³ The wording of this authorization is shown in Sidebar 1³

To expand access to COVID-19 treatments, the U.S. Department of Health and Human Services (HHS) released the 9th amendment to the Public Readiness and Emergency Preparedness (PREP) Act in September 2021.³² The 9th amendment to the COVID-19 PREP Act Declaration provides liability immunity to and expands the scope of authority for licensed pharmacists to order and administer select COVID-19 therapeutics to populations authorized by the FDA and for pharmacy technicians and pharmacy interns to administer COVID-19 therapeutics to populations authorized by the FDA when the following criteria are meet:

• The COVID-19 therapeutic must be authorized, approved, licensed, or cleared by the FDA.
• In the case of a licensed pharmacist ordering a COVID-19 therapeutic, the therapeutic must be:
• ordered for subcutaneous, intramuscular, or oral administration and
• in accordance with the FDA approval, authorization, clearance, or licensing.
• To administer IM or SC injections, the pharmacist or pharmacy technician must complete an ACPE training program on injection technique.

Initially, the benefits of the recent PREP Act amendment were limited by the FDA, which failed to extend prescribing rights of COVID-19 antiviral therapies to pharmacists. This still applies to most other antiviral therapies including the other approved oral agent. The FDA Fact Sheet accompanying the authorization of molnupiravir states, “Lagevrio may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs in the therapeutic class to which Lagevrio belongs (i.e., anti-infectives).”¹⁸ Pharmacy organizations are expected to continue advocating for broader prescribing and distribution authorization as the pandemic continues.³¹

Conclusion

COVID-19 antiviral therapies are unfamiliar to many pharmacists, physicians, and others involved in patient care due to the recent authorization by the FDA. Integrating new treatments into the healthcare system involves a multidisciplinary effort that includes pharmacists and is often spearheaded by pharmacists who are a reliable educational source for patients and prescribers.³³ Pharmacists are well positioned to provide comprehensive, timely COVID-19 services including vaccination, testing, and in some cases directly prescribing an antiviral therapy, which can help facilitate the window of early treatment. In addition, pharmacists have expert training and experience in assessing and intervening upon potential drug interactions with antivirals when appropriate.

References

1. Amariles P, Ledezma-Morales M, Salazar-Ospina A, Hincapié-García JA. Pharmacist's Role and Pharmaceutical Care During the COVID-19 Pandemic. Adv Exp Med Biol. 2021;1318:605-622.
2. Johnston K, O'Reilly CL, Cooper G, Mitchell I. The burden of COVID-19 on pharmacists. J Am Pharm Assoc (2003). Mar-Apr 2021;61(2):e61-e64.
3. U.S. Food & Drug Administration (FDA). Coronavirus (COVID-19) Update: FDA Authorizes Pharmacists to Prescribe Paxlovid with Certain Limitations. July 6, 2022. Available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-pharmacists-prescribe-paxlovid-certain-limitations.
4. Centers for Disease Control and Prevention (CDC). Interim clinical considerations for use of COVID-19 vaccines currently authorized in the United States. Updated Aug 6, 2021. Available at: https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html.
5. Centers for Disease Control and Prevention (CDC). Guidance for implementing COVID-19 prevention strategies in the context of varying community transmissions levels and vaccination coverage. Morbid Mortal Wkly Rep (MMWR). July 30, 2021;70(30:1044-1047.
6. Pfizer Reports Additional Data on PAXLOVID™ Supporting Upcoming New Drug Application Submission to U.S. FDA. Press release. June 14, 2022. Available at: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-reports-additional-data-paxlovidtm-supporting.
7. National Institutes of Health (NIH). COVID-19 Treatment Guidelines. Therapeutic Management of Nonhospitalized Adults With COVID-19. Updated April 29, 2022. Available at: https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/nonhospitalized-adults--therapeutic-management/.
8. U.S. Food & Drug Administration (FDA). FDA Updates on Paxlovid for Health Care Providers. Updated May 5, 2022. Available at: https://www.fda.gov/drugs/news-events-human-drugs/fda-updates-paxlovid-health-care-providers.
9. National Institutes of Health (NIH). COVID-19 Treatment Guidelines. Anti-SARS-CoV-2 Monoclonal Antibodies. Updated August 4, 2021. Available at: https://www.covid19treatmentguidelines.nih.gov/therapies/anti-sars-cov-2-antibody-products/anti-sars-cov-2-monoclonal-antibodies/.
10. National Institutes of Health (NIH). COVID-19 Treatment Guidelines Panel’s Statement on the Emergency Use Authorizations of Anti-SARS-CoV-2 Monoclonal Antibodies for the Treatment of COVID-19. Updated June 11, 2021. Available at: https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-anti-sars-cov-2-monoclonal-antibodies-eua/.
11. Fischer W, Eron JJ, Holman W, et al. Molnupiravir, an Oral Antiviral Treatment for COVID-19. medRxiv. Jun 17, 2021. Available at: https://www.medrxiv.org/content/10.1101/2021.06.17.21258639v1.
12. Pfizer seeks emergency use authorization for novel COVID-19 oral antiviral candidate. Press release. Nov 16, 2021. Available at: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-seeks-emergency-use-authorization-novel-covid-19.
13. U.S. Food & Drug Administration (FDA). Fact Sheet For Healthcare Providers: Emergency Use Authorization For Paxlovid. Updated Dec 21, 2021. Available at: https://www.fda.gov/media/155050/download.
14. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. Apr 14 2022;386(15):1397-1408.
15. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. Feb 10 2022;386(6):509-520.
16. Study of MK-4482 for Prevention of Coronavirus Disease 2019 (COVID-19) in Adults (MK-4482-013) (MOVe-AHEAD). ClinicalTrials.gov. NCT04939428.
17. Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study. Press release. Oct 1, 2021. Available at: https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/.
18. U.S. Food & Drug Administration (FDA). Fact Sheet for Healthcare Providers: Emergency Use Authorization for Lagevrio (molnupiravir) Capsules. Updated March 2022. Available at: https://www.fda.gov/media/155054/download.
19. Gottlieb RL, Vaca CE, Paredes R, et al. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med. Jan 27 2022;386(4):305-315.
20. Veklury (remdesivir) for injection, for intravenous use (package insert). Foster City, CA: Gilead Sciences. Revised April 2022.
21. Centers for Disease Control and Prevention (CDC). Interim clinical considerations for COVID-19 treatment in outpatients. Updated June 15, 2022. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/outpatient-treatment-overview.html.
22. Westendorf K, Žentelis S, Wang L, et al. LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants. Cell Rep. May 17 2022;39(7):110812.
23. Food and Drug Administration (FDA). Fact Sheet for Healthcare Providers: EUA for Bebtelovimab. Updated May 17, 2022. Available at: https://www.fda.gov/media/156152/download.
24. National Institutes of Health. Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Concomitant Medications. Updated May 13, 2022. Available at: https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/ritonavir-boosted-nirmatrelvir--paxlovid-/paxlovid-drug-drug-interactions/.
25. University of Liverpool. COVID-19 Drug Interaction Checker. Available at: https://www.covid19-druginteractions.org/.
26. National Institutes of Health. COVID-19 Treatment Guidelines. The COVID-19 Treatment Guidelines Panel's Statement on Potential Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Concomitant Medications. Updated Dec 30, 2021. Available at: https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-paxlovid-drug-drug-interactions/.
27. Centers for Disease Control and Prevention (CDC). CDC Health Advisory: COVID-19 Rebound After Paxlovid. May 24, 2022. Available at: https://emergency.cdc.gov/han/2022/pdf/CDC_HAN_467.pdf.
28. Ranganath N, O'Horo JC, Challener DW, et al. Rebound Phenomenon after Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease-2019 in High-Risk Persons. Clin Infect Dis. Jun 14 2022; doi: 10.1093/cid/ciac481. Online ahead of print;
29. Gurnani PK, Peksa GD, Panos NG, DeMott JM. Under the Microscope: A Look Into the Role of Critical Care Pharmacists During the COVID-19 Pandemic. J Pharm Pract. May 18 2021:8971900211013991.
30. American Association of Colleges of Pharmacy (AACP). Modification to EUAs for Oral Antivirals Needed to Achieve Potential of “Test to Treat” Initiative. Press Release. March 11, 2022. Available at: https://www.aacp.org/article/pharmacist-groups-call-biden-administration-remove-limits-prescribing-covid-treatments.
31. American Society of Hospital Pharmacists (ASHP). FDA’s Decision to Block Pharmacists from Ordering COVID-19 Oral Antivirals Will Hurt COVID Positive Patients, National Pharmacy Groups Warn. Press release. Dec 22, 2021. Available at: https://www.ashp.org/News/2021/12/22/fdas-decision-to-block-pharmacists-from-ordering-covid19-oral-antivirals?loginreturnUrl=SSOCheckOnly.
32. U.S. Department of Health & Human Services. Public Health Emergency (PHE). Expanding Access to COVID 19 Therapeutics. September 13, 2021. Available at: https://www.phe.gov/Preparedness/legal/prepact/Pages/PREPact-NinethAmendment.aspx#:~:text=HHS%20PREP%20Act%20Declaration%3A%209th%20Amendment&text=To%20support%20this%20priority%20effort,pharmacy%20technicians%2C%20and%20pharmacy%20interns.
33. Elbeddini A, Prabaharan T, Almasalkhi S, Tran C. Pharmacists and COVID-19. Journal of Pharmaceutical Policy and Practice. 2020/06/19 2020;13(1):36.

Back to Top