by Zoe McQueen, Doctor of Pharmacy Candidate

Since 2019, the coronavirus (COVID-19) pandemic has run rampant throughout the world. To date, more than 430 million cases have been confirmed, with nearly 6 million deaths, worldwide.1 Of these confirmed cases, many require hospitalization. This risk of hospitalization is increased significantly in patients with comorbidities such as diabetes, obesity, hypertension, and chronic kidney disease.2 There have been many strategies to prevent and treat the SARS-CoV-2 infection. Several COVID-19 vaccines are now approved and have been repeatedly shown in clinical trials to significantly reduce the rate of hospitalization and death in patients.3 Several parenteral monoclonal antibody therapies have also been used to both prevent and treat COVID-19 including REGEN-COV (casirivimab and imdevimab), bamlanivimab and etesevimab, sotrovimab, tocilizumab, and bebtelovimab.4  Not all of these therapies are effective against all of the SARS-CoV-2 variants.4 Although parental therapies have undoubtedly saved lives and reduced the number of hospitalizations, other options are needed due to their limited availability as well as the challenges in administering these therapies. Recently, two oral drugs have been granted Emergency Use Authorization (EUA) for the treatment of mild-to-moderate COVID-19 infections.

On December 22, 2021, PaxlovidTM was granted EUA for the treatment of mild-to-moderate COVID-19 infection in patients at least 12 years of age and who weigh at least 40 kilograms (~90 lbs). Manufactured by Pfizer, PaxlovidTM is a product that contains two separate, co-packaged drugs: nirmatrelvir, a SARS-CoV-2 protease inhibitor, and ritonavir, an HIV-1 protease inhibitor and CYP3A4 inhibitor. Patients must have a positive test result of a direct SARS-CoV-2 test and be at high risk of progression to a severe infection requiring hospitalization or potentially resulting in death. PaxlovidTM must be initiated within 5 days of symptom onset. It is not authorized for use in patients currently hospitalized or for pre-exposure or post-exposure prophylaxis. Each”dose” contains 300 mg nirmatrelvir (two 150 mg tablets) and 100 mg of ritonavir (one 100 mg tablet). All three tablets should be taken at the same time, twice daily for five days, with or without food. In patients with eGFR between 30 and 60 mL/min, the dose should be reduced to 150 mg of nirmatrelvir (one tablet) with 100 mg of ritonavir (one table), twice daily, for five days. PaxlovidTM is not recommended in patients with severe renal impairment (eGFR < 30 mL/min). Co-administration with CYP3A4 inducers or drugs dependent on CYP3A4 for clearance is not recommended as ritonavir is a CYP3A4 inhibitor. The most common adverse events include diarrhea, dysgeusia (altered taste), hypertension, and myalgia. Because this product contains ritonavir, PaxlovidTM may lead to HIV-1 drug resistance in patients with an undiagnosed (or uncontrolled) HIV-1 infection.5-6

Just two days later, on December 23, 2021, Molnupiravir was granted EUA for the treatment of mild-to-moderate COVID-19. Molnupiravir, by Merck & Co., is a nucleoside analog that inhibits SARS-CoV-2 replication by viral mutagenesis. Molnupiravir is authorized for the treatment of adults only (18 years of age or older). Patients must have a positive test result from a direct SARS-CoV-2 test and be at high risk of progression to severe infection that might result in hospitalization or death. It should be used in patients currently hospitalized or for pre- or post-exposure prophylaxis. Similar to PaxlovidTM, molnupiravir must be initiated within 5 days of symptom onset. The dose is 800 mg (4-200 mg capsules) taken twice daily for five days, with or without food. No dose adjustments are required in patients with renal or hepatic impairment. The most common adverse events reported in clinical trials were diarrhea, nausea, and dizziness.7-8

Although the PREP Act authorizes pharmacists to order and administer some COVID-19 treatments, both oral therapies (which are not yet FDA approved) still require a prescription from an authorized prescriber based on state laws – specifically a physician, advanced practice registered nurse, or physician assistant. Due to the differences between the two therapies, pharmacists will play a key role in providing information about the two drugs to prescribers. Below is a helpful chart listing the most relevant prescribing and dispensing information for each drug to use as a reference in the future.

Brief Summary – Oral COVID-19 Therapies Compared

PaxlovidTMMolnupiravir
IndicationMild-to-moderate treatment of COVID-19 infection in patients 12 years of age and older, weighing at least 40 kgMild-to-moderate treatment of COVID-19 infection in patients 18 years of age and older
InitiationWithin 5 days of symptom onsetWithin 5 days of symptom onset
Dosage300 mg nirmatrelvir (2 x 150 mg tablets) with 100 mg ritonavir (1 x 100 mg tablet), twice daily800 mg (4 x 200 mg capsules), twice daily
Duration5 days5 days
Renal dose adjustmenteGFR 30-60 mL/min: decrease dose of nirmatrelvir to 150 mg twice daily; ritonavir dose remains the sameNo renal dose adjustment is necessary
Adverse eventsDysgeusia, diarrhea, hypertension, myalgiaDiarrhea, nausea, and dizziness
Clinical pearlsAvoid co-administration with drugs dependent on CYP3A4 clearance and CYP3A4 inducers; may lead to the risk of HIV-1 drug resistanceDo not administer to those less than 18 years of age due to the potential risk of bone and cartilage toxicity
Use during pregnancy or lactationNot recommendedNot recommended

References

  1. WHO coronavirus (COVID–19) dashboard. Geneva: World Health Organization, 2022.
  2. Ko JY, Danielson ML, Town M, et al. Risk factors for coronavirus disease 2019 (COVID-19)–associated hospitalization: COVID-19–associated hospitalization surveillance network and behavioral risk factor surveillance system. Clin Infect Dis 2021;72(11):e695-e703.
  3. Moline HL, Whitaker M, Deng L, et al. Effectiveness of COVID-19 Vaccines in Preventing Hospitalization Among Adults Aged ≥65 Years — COVID-NET, 13 States, February–April 2021. MMWR Morb Mortal Wkly Rep 2021;70:1088-1093.
  4. Centers of Medicare and Medicaid Services. (n.d.). COVID-19 monoclonal antibodies. CMS. Retrieved February 26, 2022.
  5. Paxlovid [package insert]. Pfizer Pharmaceuticals. 2021
  6. FDA. Coronavirus (COVID-19) update: FDA authorizes first oral antiviral for treatment of covid-19. U.S. Food and Drug Administration. Retrieved February 26, 2022.
  7. Molnupiravir [package insert]. Merck & Co. 2021
  8. FDA. Coronavirus (COVID-19) update: FDA authorizes additional oral antiviral for treatment of covid-19 in certain adults. U.S. Food and Drug Administration. Retrieved February 26, 2022.