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

From the Guidelines

Outpatient COVID-19 treatment should prioritize nirmatrelvir-ritonavir combination therapy or molnupiravir for high-risk patients within 5 days of symptom onset, as recommended by the American College of Physicians 1. The treatment options for outpatient COVID-19 include:

• Nirmatrelvir-ritonavir combination therapy, which consists of 300mg nirmatrelvir plus 100mg ritonavir taken twice daily for 5 days, started within 5 days of symptom onset.
• Molnupiravir, dosed at 800mg twice daily for 5 days, for patients who are not eligible for nirmatrelvir-ritonavir combination therapy. These medications work by interfering with viral replication, with Paxlovid inhibiting viral protease and molnupiravir causing viral RNA mutations. Treatment eligibility typically requires risk factors for severe disease, including age over 65, immunocompromised status, or chronic medical conditions. It is also important to note that ivermectin and sotrovimab are not recommended for outpatient COVID-19 treatment, as stated in the practice points from the American College of Physicians 1. Symptomatic care remains important for all patients, including adequate hydration, rest, and fever control with acetaminophen or NSAIDs. Drug interactions must be carefully evaluated, particularly with Paxlovid, which may interact with many common medications. The American College of Physicians provides living, rapid practice points for the outpatient treatment of confirmed COVID-19, which are updated regularly to reflect the latest evidence 1.

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.

The treatment option for outpatient Covid-19 is PAXLOVID (nirmatrelvir tablets; ritonavir tablets), which 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.

• The dosage is 300 mg nirmatrelvir with 100 mg ritonavir, taken twice daily for 5 days.
• Treatment should be initiated as soon as possible after diagnosis and within 5 days of symptom onset 2.

From the Research

Outpatient Covid-19 Treatment Options

The following are treatment options for outpatient Covid-19 treatment:

• Molnupiravir: an oral antiviral drug that can be used to treat patients with mild to moderate Covid-19 who are at high risk for progressing to severe disease 3, 4, 5.
• Nirmatrelvir-Ritonavir (Paxlovid): an oral antiviral drug that can be used to treat patients with mild to moderate Covid-19 who are at high risk for progressing to severe disease 3, 6, 4, 7.
• Remdesivir: an antiviral drug that can be used to treat patients with mild to moderate Covid-19 who are at high risk for progressing to severe disease 6, 4.
• Sotrovimab: a monoclonal antibody that can be used to treat patients with Covid-19 who are at high risk for progressing to severe disease, although its efficacy against certain variants is uncertain 6.
• Budesonide inhalation: may be offered to Covid-19 patients at risk of a severe course, according to an off-label recommendation of the German College of General Practitioners and Family Physicians 6.

Treatment Considerations

When considering treatment options, the following factors should be taken into account:

• The patient's risk factors for severe disease, such as age, comorbidities, and vaccination status 3, 6, 4.
• The timing of treatment, with most treatments being most effective when started within 5 days of symptom onset 3, 6, 4, 5.
• Potential drug interactions, particularly with Nirmatrelvir-Ritonavir 3, 6.
• The efficacy of the treatment against specific variants of the virus, such as Omicron 7.

Treatments to Avoid

The following treatments are not recommended for outpatient Covid-19 treatment:

• Azithromycin 6, 4.
• Chloroquine or hydroxychloroquine 4.
• Ivermectin 6, 4.
• Nitazoxanide 4.
• Lopinavir-ritonavir combination therapy 4.
• Casirivimab-imdevimab combination therapy, unless effective against the locally circulating variant or subvariant 4.
• Regdanvimab, unless effective against the locally circulating variant or subvariant 4.
• Sotrovimab, unless effective against the locally circulating variant or subvariant 4.
• Convalescent plasma 4.
• Ciclesonide 4.
• Fluvoxamine 4.