What is the common outpatient treatment regimen for Coronavirus disease (COVID-19)?

From the Guidelines

The most effective outpatient treatment regimen for COVID-19, based on the latest evidence from 2024, involves the use of antiviral medications such as nirmatrelvir–ritonavir combination therapy or molnupiravir for symptomatic patients at high risk for progressing to severe disease, initiated within 5 days of symptom onset. According to the American College of Physicians' living, rapid practice points, updated in 2024 1, the treatment approach focuses on managing symptoms and preventing disease progression in high-risk patients. For eligible patients, the recommended antiviral medications are:

• Nirmatrelvir–ritonavir combination therapy, which should be considered for symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease.
• Molnupiravir, which is also recommended for similar patient groups. Key points to consider in the treatment regimen include:
• Initiating treatment within 5 days of symptom onset for maximum effectiveness
• Monitoring for worsening symptoms that may require immediate medical attention
• Isolating for at least 5 days from symptom onset to prevent transmission
• Managing symptoms with rest, hydration, and over-the-counter medications like acetaminophen or ibuprofen for fever and pain, as needed. It is crucial to note that ivermectin and sotrovimab are not supported for use in treating patients with confirmed mild to moderate COVID-19 in the outpatient setting, based on the latest practice points 1.

From the FDA Drug Label

PAXLOVID 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 common outpatient treatment regimen for Covid-19 is PAXLOVID, which consists of nirmatrelvir and ritonavir. The recommended dosage is 300 mg nirmatrelvir with 100 mg ritonavir, taken twice daily for 5 days, and should be initiated as soon as possible after diagnosis and within 5 days of symptom onset 2.

From the Research

Common Outpatient Treatment Regimens for Covid

• Molnupiravir and nirmatrelvir-ritonavir are two oral antivirals that have received emergency use authorization from the U.S. Food and Drug Administration for the treatment of mild to moderate coronavirus disease (COVID-19) in the outpatient setting 3, 4.
• These treatments are recommended for patients who are within 5 days of the onset of symptoms and are at high risk for progressing to severe disease 3, 4, 5, 6.
• Molnupiravir should not be used in children or pregnant persons due to concerns about potential toxicity, and reliable contraception should be used in persons of childbearing potential 4.
• Nirmatrelvir-ritonavir may cause significant drug-to-drug interactions that limit its use in persons taking certain medications metabolized by certain cytochrome P450 enzymes 3, 4.
• The American College of Physicians recommends considering molnupiravir and nirmatrelvir-ritonavir combination therapy to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease 5, 6.

Treatment Duration and Administration

• Both molnupiravir and nirmatrelvir-ritonavir are taken orally twice daily for 5 days 3, 4.
• The treatments should be started within 5 days of symptoms onset 3, 4, 5, 6.

Efficacy and Safety

• Nirmatrelvir-ritonavir has been shown to reduce the risk of all-cause mortality and hospital admission or death in patients with mild COVID-19 7.
• Molnupiravir and nirmatrelvir-ritonavir have been shown to decrease severe outcomes (hospitalizations and death) with adjusted relative risk reductions of 30% and 88%, respectively 4.
• The treatments are generally well-tolerated, but may cause adverse events such as dysgeusia and diarrhea 7, 4.