Recommended Antiviral Therapies for COVID-19
Paxlovid (nirmatrelvir/ritonavir) is the preferred antiviral therapy for high-risk patients with mild-to-moderate COVID-19, while molnupiravir should be considered only when Paxlovid is contraindicated or unavailable. 1
Patient Selection for Antiviral Therapy
High-Risk Patients
- Treatment should focus on patients at high risk for disease progression, including:
- Advanced age (especially ≥65 years)
- Uncontrolled chronic medical conditions
- Immunocompromised status
- Unvaccinated status
- Pregnancy 1
Timing of Treatment
- Antivirals must be initiated within 5 days of symptom onset for optimal effectiveness 1, 2
- Earlier initiation is associated with better outcomes 3
First-Line Treatment: Paxlovid (Nirmatrelvir/Ritonavir)
Efficacy
- Reduces hospitalization risk by 86% and mortality by up to 100% in high-risk patients 1
- Real-world data shows 39% reduction in hospitalization risk and 61% reduction in death risk 3
- Most effective in older patients (65+ years) 3
Dosing
- Standard dose: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 1, 4
- 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 4
- Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 4
Contraindications and Precautions
- History of hypersensitivity to nirmatrelvir or ritonavir 4
- Significant drug-drug interactions (major concern) 4, 5
- Co-administration with drugs highly dependent on CYP3A for clearance 4
- Co-administration with potent CYP3A inducers 4
Common Adverse Effects
Alternative Treatment: Molnupiravir
When to Consider
- When Paxlovid is contraindicated due to drug interactions
- When Paxlovid is unavailable 1
Efficacy
- Less effective than Paxlovid, with approximately 30% relative risk reduction in hospitalization and death 6
Contraindications
Alternative Treatment: Remdesivir
When to Consider
- When Paxlovid is contraindicated due to drug interactions
- When molnupiravir is contraindicated 1
Administration
- Requires intravenous administration over 3 days 1
- May reduce hospital admission more than molnupiravir 7
Efficacy
- Probably results in important reduction in risk of hospital admission (moderate certainty)
- Probably little or no impact on mortality (moderate certainty) 7
Important Clinical Considerations
Drug Interaction Management
- Prior to prescribing Paxlovid:
- Options for managing interactions include:
- Temporary pause of interacting medication during 5-day Paxlovid course
- Dose adjustment of interacting medication
- Selection of alternative COVID-19 treatment 5
Special Populations
- Pregnancy: Paxlovid is an option for pregnant people with COVID-19 1
- Breastfeeding: Not contraindicated during Paxlovid treatment 1
- HIV: Caution in uncontrolled/undiagnosed HIV-1 infection due to potential for developing resistance to HIV protease inhibitors 4
Common Pitfalls to Avoid
- Initiating treatment beyond 5 days of symptom onset (reduced efficacy)
- Failing to screen for drug interactions before prescribing Paxlovid
- Using antibiotics without clear evidence of bacterial infection
- Combining antiviral therapies (not recommended) 7, 1
- Inappropriate use in patients with severe hepatic impairment
Current WHO Recommendation
- WHO currently suggests not using nirmatrelvir/ritonavir in low-risk patients with non-severe COVID-19 (conditional recommendation) 7
- This differs from other guidelines that strongly recommend Paxlovid for high-risk patients 1
- The difference reflects varying interpretations of benefit-risk balance across different patient populations