What are the recommended antiviral medications for the treatment of Covid-19?

Recommended Antiviral Medications for COVID-19

Nirmatrelvir/ritonavir (Paxlovid) is the preferred first-line antiviral medication for high-risk patients with mild to moderate COVID-19, with remdesivir as an alternative when Paxlovid is contraindicated. 1

Patient Selection for Antiviral Therapy

Antiviral therapy should be targeted to high-risk patients who will benefit most:

• High-risk patients include:

  • Advanced age (especially ≥65 years)
  • Uncontrolled chronic medical conditions
  • Immunocompromised status
  • Unvaccinated status
  • Pregnancy 1

• Timing is critical:

  • Treatment must be initiated within 5 days of symptom onset for Paxlovid and molnupiravir
  • Treatment must be initiated within 7 days of symptom onset for remdesivir 1, 2

First-Line Treatment: Nirmatrelvir/Ritonavir (Paxlovid)

Paxlovid is the preferred first-line treatment for high-risk outpatients with mild-to-moderate COVID-19, showing:

• 86% reduction in hospitalization risk
• 100% reduction in mortality compared to placebo 1

Dosing:

• Standard dose: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), taken together twice daily for 5 days 3
• Renal dose adjustments:
  • Moderate impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir, twice daily for 5 days
  • Severe impairment (eGFR <30 mL/min): Day 1: 300 mg nirmatrelvir with 100 mg ritonavir once; Days 2-5: 150 mg nirmatrelvir with 100 mg ritonavir once daily 3

Important Precautions:

• Drug interactions: Ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications
• Before prescribing:
  • Review all patient medications for potential drug-drug interactions
  • Determine if concomitant medications require dose adjustment, interruption, or additional monitoring 3, 4, 5
• Contraindications:
  • History of hypersensitivity to nirmatrelvir or ritonavir
  • Co-administration with drugs highly dependent on CYP3A for clearance
  • Co-administration with potent CYP3A inducers 3

Second-Line Treatment: Remdesivir

When Paxlovid is contraindicated due to drug interactions or unavailable:

Dosing:

• Adults and pediatric patients ≥40 kg:
  • Loading dose: 200 mg IV on Day 1
  • Maintenance dose: 100 mg IV daily from Day 2
• Duration:
  • Non-hospitalized patients: 3 days
  • Hospitalized patients not requiring mechanical ventilation/ECMO: 5 days
  • Hospitalized patients requiring mechanical ventilation/ECMO: 10 days 2

Advantages:

• Moderate certainty evidence for reducing hospital admission
• Moderate certainty evidence for little/no impact on mortality 1

Disadvantages:

• Requires intravenous administration over 3 days 1

Third-Line Treatment: Molnupiravir

Consider when Paxlovid and remdesivir are contraindicated or unavailable:

Important limitations:

• Less effective than Paxlovid and remdesivir
• Contraindicated in pregnancy due to mutagenesis concerns
• Contraindicated in children 1, 6

Regional Variations in Recommendations

It's important to note that antiviral recommendations have varied by country and evolved over time:

• Early in the pandemic (2020), countries like Italy, Russia, France, Netherlands, Spain, and China recommended various antivirals including lopinavir/ritonavir, chloroquine/hydroxychloroquine, interferons, and remdesivir 7
• Current guidelines have evolved to prioritize newer antivirals with better efficacy data, particularly nirmatrelvir/ritonavir 1

Common Pitfalls to Avoid

• Delayed initiation: Failing to start treatment within the recommended timeframe (5 days for Paxlovid/molnupiravir, 7 days for remdesivir) significantly reduces efficacy 1
• Missing drug interactions: Not screening for drug interactions before prescribing Paxlovid can lead to serious adverse events 3, 4, 5
• Inappropriate antibiotic use: Using antibiotics without clear evidence of bacterial infection is not recommended 1
• Combining antiviral therapies: Not recommended due to lack of evidence and potential for increased adverse effects 1
• Using ineffective treatments: Ivermectin and sotrovimab are not recommended for outpatient treatment of COVID-19 1

Real-world effectiveness data supports the use of Paxlovid, with a recent large study showing a 39% reduction in hospitalization risk and 61% reduction in death risk, with particularly strong benefits for patients aged 65+ years 8.