Oral Antivirals for High-risk COVID-19 Patients

Lauren Biehle, PharmD, BCPS, BCIDP; Jeremy W. Vandiver, PharmD, BCPS

US Pharmacist. 2022;47(7):34-41.

Conclusion

Despite limitations noted above, the development, authorization, and clinical availability of effective oral antivirals to prevent severe COVID-19 are important steps in combating this disease. There will be more research in the future to elucidate whether there is clinical benefit for N-R and molnupiravir in other situations (e.g., patients with acute infection without high-risk features, patients with long COVID-19 symptoms). Given that both molnupiravir and N-R have their own unique considerations, pharmacists will play an important role in patient selection, dosage adjustment, drug interaction management, dispensing, and patient counseling.

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Abstract and Introduction
Ritonavir-boosted Nirmatrelvir (Paxlovid)
Molnupiravir (Lagevrio)
Conclusion
References

Table 1. Select Medications That Interact With Ritonavir-Boosted Nirmatrelvir ^a
Alternative COVID-19 Therapy Recommended if Receiving Medication	Withhold Concomitant Medication Listed or Recommend Alternative COVID-19 Therapy
Amiodarone	Alprazolam
Carbamazepine	Atorvastatin
Clopidogrel	Clonazepam
Colchicine (if renal or hepatic impairment)	Codeine
Dofetilide	Cyclosporine (after consultation with specialist provider)
Dronedarone	Diazepam
Flecainide	Everolimus (after consultation with specialist provider)
Glecaprevir-pibrentasvir	Fentanyl
Lurasidone	Lovastatin
Phenobarbital	Midazolam
Phenytoin	Rivaroxaban
Ranolazine	Rosuvastatin
Rifampin	Simvastatin

^aNot comprehensive. All medication regimens should be critically evaluated for drug-drug interactions prior to initiating ritonavir-boosted nirmatrelvir as treatment of COVID-19. Source: Adapted from References 3, 15.

Table 2. Comparison of Ritonavir-Boosted Nirmatrelvir and Molnupiravir
	Ritonavir-Boosted Nirmatrelvir	Molnupiravir
Indication	Age 2 years and older positive for SARS-CoV-2 who are at high risk for progression to severe COVID-19	Age 18 years and older positive for SARSCoV-2 who are at high risk for progression to severe COVID-19
Mechanism	Protease inhibitor (Mpro)	Nucleoside analog
Dosing	300 mg nirmatrelvir (two 150-mg tablets) with 100-mg ritonavir every 12 hours	Molnupiravir 800 mg (four 200-mg capsules) every 12 hours
Renal dose adjustment	Adjust dose for GFR 30–59 mL/min/1.73 m²; not recommended for GFR <30	None
Duration	5 days	5 days (do NOT use unless patient can be adherent to full treatment course)
Efficacy	88% reduction in hospitalization and death when started within 5 days of symptom onset based on EPIC-HR (n = 2,246)	31% reduction in hospitalization and death when started within 5 days of symptom onset based on MOVe-OUT (n = 1,433)
Adverse effects	Dysgeusia, diarrhea	Diarrhea, nausea, dizziness
Pregnancy/lactation	No available human data for nirmatrelvir in pregnancy/lactation; see text for details	Not recommended in pregnancy Not recommended in breastfeeding during treatment and for 4 days after last dose
Contraindications	Hypersensitivity to nirmatrelvir, ritonavir, or components; administration with interacting medications that may significantly increase or decrease concentrations of nirmatrelvir or ritonavir	None known
Drug interactions	Significant due to ritonavir as strong 3A4 inhibitor; all regimens should be evaluated for drug interactions prior to initiation	None known

EPIC-HR: Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients; GFR: glomerular filtration rate.
Source: References 3, 19.

Table 3. Patient Prioritization for Outpatient SARS-CoV-2 Therapies When Supplies and Logistics Are Limited
Tier	Patient Populations
1: Highest risk for severe disease	Moderately or severely immunocompromised patients^a Unvaccinated patient aged ≥75 years Unvaccinated patients aged ≥65 years with clinical risk factors
2: Higher risk for severe disease	Unvaccinated patients aged 65 to 74 years Unvaccinated patients aged younger than 65 years with clinical risk factors
3: High risk for severe disease	Vaccinated patients aged ≥75 years Vaccinated patients aged ≥65 years with clinical risk factors
4: Risk for severe disease	Vaccinated patients aged ≥65 years Vaccinated patients aged younger than 65 years with clinical risk factors^b

^aImmunocompromised conditions include active cancer treatment, organ or stem cell transplantation on immunosuppressive therapies, moderate-severe primary immunodeficiency, advanced or untreated HIV infection, and patients on high-dose corticosteroids (≥20 mg of prednisone or equivalent per day for ≥2 weeks) or other biologic immunosuppressive or immunomodulatory therapies (particularly B cell–depleting therapies, Bruton's tyrosine kinase inhibitors, and chimeric antigen receptor T-cell therapy).
^bClinical risk factors include cancer, cardiovascular disease, chronic lung disease, chronic kidney disease, chronic liver disease, diabetes mellitus, obesity, pregnancy, sickle cell disease, smoking (current and former), and tuberculosis.
Source: Reference 2.

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Oral Antivirals for High-risk COVID-19 Patients

Conclusion

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