What are the treatment options for outpatient management of Covid-19 (Coronavirus disease 2019)?

From the Guidelines

Outpatient treatment for COVID-19 should prioritize nirmatrelvir-ritonavir combination therapy for high-risk patients with mild to moderate symptoms, as it has been shown to reduce the risk of severe disease and hospitalization 1.

Key Considerations

• Nirmatrelvir-ritonavir combination therapy is the preferred antiviral treatment for eligible patients, given as 300mg nirmatrelvir with 100mg ritonavir twice daily for 5 days, started within 5 days of symptom onset.
• Molnupiravir (800mg twice daily for 5 days) may be considered for patients who cannot take nirmatrelvir-ritonavir combination therapy, although it is less effective.
• Symptomatic treatment includes acetaminophen or NSAIDs for fever and pain, adequate hydration, and rest.
• Patients should self-isolate according to current guidelines, typically 5 days from symptom onset if improving and fever-free for 24 hours without medication.

Treatment Decisions

• Treatment decisions should be based on individual risk factors for severe disease, including age over 65, immunocompromised status, obesity, diabetes, and cardiovascular disease.
• Important drug interactions must be checked before prescribing nirmatrelvir-ritonavir combination therapy.

Evidence Summary

• The American College of Physicians recommends considering nirmatrelvir-ritonavir combination therapy and molnupiravir for outpatient treatment of COVID-19 in high-risk patients 1.
• The evidence suggests that nirmatrelvir-ritonavir combination therapy reduces the risk of severe disease and hospitalization, while molnupiravir may also be effective although to a lesser extent.

From the FDA Drug Label

PAXLOVID which includes nirmatrelvir, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro: also referred to as 3CLpro or nsp5 protease) inhibitor, and ritonavir, an HIV-1 protease inhibitor and CYP3A inhibitor, is indicated for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. Initiate PAXLOVID treatment as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. Dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all 3 tablets taken together twice daily for 5 days.

The treatment option for outpatient management of Covid-19 is PAXLOVID (nirmatrelvir and ritonavir), which is indicated for the treatment of mild-to-moderate COVID-19 in adults at high risk for progression to severe COVID-19. The dosage is 300 mg nirmatrelvir with 100 mg ritonavir, taken twice daily for 5 days, and treatment should be initiated as soon as possible after diagnosis and within 5 days of symptom onset 2. Key considerations include:

• High risk for progression to severe COVID-19
• Initiation of treatment within 5 days of symptom onset
• Dosage and administration as specified
• Potential drug interactions and contraindications, such as history of clinically significant hypersensitivity reactions or co-administration with certain drugs.

From the Research

Outpatient Treatment Options for COVID-19

The following are treatment options for outpatient management of COVID-19:

• Unvaccinated COVID-19 outpatients with at least one risk factor for a severe disease course may be treated in the early phase of the disease with sotrovimab, remdesivir, or nirmatrelvir/ritonavir 3
• Molnupiravir may also be used for such patients if no other clinically appropriate treatment options are available 3, 4, 5
• Immunosuppressed persons with COVID-19 who are at high risk, and whose response to vaccination is expected to be reduced, ought to be treated with sotrovimab 3
• COVID-19 patients at risk of a severe course may be offered budesonide inhalation, according to an off-label recommendation of the German College of General Practitioners and Family Physicians 3
• Thrombo-embolism prophylaxis with low-molecular-weight heparin may be given to elderly patients or those with a pre-existing illness 3

Medications to Avoid

The following medications should not be used for the outpatient treatment of COVID-19:

• Azithromycin 3, 4
• Ivermectin 3, 4
• Systemic steroids 3
• Vitamin D 3
• Fluvoxamine 3, 4
• Colchicine 3
• Acetylsalicylic acid 3
• Casirivimab-imdevimab combination therapy, unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation 4
• Regdanvimab, unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation 4
• Sotrovimab, unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation 4
• Convalescent plasma 4
• Ciclesonide 4
• Lopinavir-ritonavir combination therapy 4
• Nitazoxanide 4
• Chloroquine or hydroxychloroquine 4

Additional Considerations

• The clinical efficacy of sotrovimab against infections with the omicron subtype BA.2 is uncertain at the currently used dose, as the drug has displayed reduced activity against this subtype in vitro 3
• Nirmatrelvir-ritonavir demonstrated a greater risk reduction in hospitalization and death than molnupiravir compared to placebo 5
• Both molnupiravir and nirmatrelvir-ritonavir need to be started within 5 days of symptoms onset and given for 5 days' duration 5