Outpatient COVID-19 Treatment Recommendations

Introduction to Treatment

The American College of Physicians recommends using nirmatrelvir/ritonavir (Paxlovid) as first-line therapy for high-risk outpatients with confirmed mild-to-moderate COVID-19 within 5 days of symptom onset, with molnupiravir as an alternative when Paxlovid is contraindicated or unavailable 1, 2, 3, 4

Confirmed COVID-19 with mild-to-moderate symptoms is required for treatment, as stated by the American College of Physicians 1, 5
Treatment should be initiated within 5 days of symptom onset, as recommended by the American College of Physicians 5, 6
High risk for progression includes unvaccinated status, age ≥65 years, immunosuppression, multiple comorbidities (≥3), hematological disease, or radiographic evidence of pneumonia, according to the American College of Physicians 5

The American College of Physicians recommends a mandatory medication review using a drug interaction checker before prescribing nirmatrelvir/ritonavir (Paxlovid) 7
Ritonavir is a strong CYP3A inhibitor, causing potentially life-threatening drug interactions, as noted by the American College of Physicians 1, 4
Nirmatrelvir/ritonavir reduces all-cause mortality and COVID-19-specific mortality, according to the American College of Physicians 1, 4

The American College of Physicians recommends using molnupiravir as an alternative treatment when nirmatrelvir/ritonavir is contraindicated or unavailable 1, 2, 3
Molnupiravir reduces all-cause mortality and time to recovery, as stated by the American College of Physicians 1, 3, 4

The American College of Physicians does not recommend using ivermectin, sotrovimab, azithromycin, systemic steroids, or vitamin D for outpatient COVID-19 treatment 1, 2, 3, 4

The American College of Physicians recommends initiating treatment as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 5, 6

The American College of Physicians recommends monitoring hepatic function if baseline liver abnormalities are present, and ensuring patient continues isolation per public health recommendations during treatment 5