Remarks

• See Section 6.1 for help to identify patients at highest risk.
• Several therapeutic options are available: see decision support tool that displays benefits and harms of nirmatrelvir-ritonavir, molnupiravir and remdesivir.
• The GDG concluded that nirmatrelvir-ritonavir represents a superior choice because it may have greater efficacy in preventing hospitalization than the alternatives, has fewer concerns with respect to harms than does molnupiravir; and is easier to administer than intravenous remdesivir and the antibodies.
• The strong recommendation in favour does not apply to pregnant women, children, or those with possible dangerous drug interactions (many drugs interact with nirmatrelvir-ritonavir, see mechanism of action).
• Nirmatrelvir-ritonavir should be administered as soon as possible after onset of symptoms, ideally within 5 days.

Practical Info Route, dosage and duration: Additional considerations are available in three summaries of practical issues (nirmatrelvir-ritonavir for COVID-19, administration of nirmatrelvir-ritonavir for COVID-19, safety and monitoring for patients receiving nirmatrelvirritonavir for COVID-19). Here follows a brief summary of key points:

• The recommended dose for nirmatrelvir-ritonavir is 300 mg (two 150 mg tablets) of nirmatrelvir and 100 mg of ritonavir every 12 hours daily for 5 days, as per the regimen evaluated in large trials informing the recommendation.
• In renal insufficiency (GFR 30–59 mL/min) the dose reduction is 150 mg of nirmatrelvir and 100 mg of ritonavir every 12 hours daily for 5 days.
• Administration should be as early as possible in the time course of the disease. In the included studies, nirmatrelvir-ritonavir was administered within 5 days of disease onset.
• The GDG concluded that nirmatrelvir-ritonavir should not be offered to children, breastfeeding or pregnant women with COVID-19. In any patient being considered for nirmatrelvir-ritonavir use, clinicians need to give serious consideration to drug interactions. The Liverpool COVID-19 drug interaction checker may be useful in this regard (24).