What is the recommended treatment for new Covid-19 (Coronavirus disease 2019) cases?

Recommended Treatment for New COVID-19 Cases

For patients with non-severe COVID-19 at high risk of hospitalization, nirmatrelvir/ritonavir (Paxlovid) is strongly recommended as the first-line treatment, administered within 5 days of symptom onset. 1

Risk Stratification and Treatment Algorithm

High-Risk Patients (Strong Recommendation)

• Dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), taken together twice daily for 5 days 1, 2
• Timing: Must be initiated within 5 days of symptom onset 1, 2
• Renal Adjustment:
  • Moderate impairment (eGFR 30-60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily 2
  • Severe impairment (eGFR <30 mL/min): 300 mg nirmatrelvir with 100 mg ritonavir on day 1, then 150 mg nirmatrelvir with 100 mg ritonavir once daily for days 2-5 2

Moderate-Risk Patients (Conditional Recommendation)

• Same dosing as high-risk patients 1
• When supplies are limited, prioritize high-risk patients 1

Low-Risk Patients

• Nirmatrelvir/ritonavir is not recommended (conditional recommendation) 1

Drug Interaction Management

Drug interactions are a major concern with nirmatrelvir/ritonavir due to ritonavir's strong CYP3A inhibition 2, 3:

1. Before prescribing:

   • Review all patient medications for potential interactions
   • Use resources like Liverpool COVID-19 Drug Interaction Tool 1
   • Determine if medications require dose adjustment, interruption, or additional monitoring

2. High-risk interactions:

   • Avoid co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations may cause serious reactions 2
   • Avoid co-administration with potent CYP3A inducers 2
   • Particular attention needed for cardiovascular medications with narrow therapeutic indices 4

Alternative Treatments When Nirmatrelvir/Ritonavir Is Contraindicated

When drug interactions or other contraindications prevent the use of nirmatrelvir/ritonavir:

1. Remdesivir: 200 mg IV on day 1, followed by 100 mg IV daily for 2 additional days (3-day course total) 1, 5

   • Most effective when initiated early, particularly within 7 days of symptom onset
   • Less convenient due to parenteral administration

2. Molnupiravir: May be considered if no other options are available, but has lower efficacy and potential safety concerns 1, 6

Special Populations

Immunocompromised Patients

• Continue antiretroviral therapy in patients with HIV 5
• Be aware of potential drug interactions between COVID-19 treatments and antiretrovirals 5

Pregnant or Breastfeeding Patients

• Nirmatrelvir/ritonavir may be considered 1

Supportive Care

For patients with respiratory symptoms:

• Low-flow oxygen for mild hypoxemia and high-flow nasal cannula for moderate hypoxemia 5
• Consider prone positioning to improve oxygenation 5
• Evaluate risk of venous thromboembolism and use low-molecular-weight heparin or unfractionated heparin for thromboprophylaxis in high-risk patients without contraindications 5

Monitoring and Follow-up

• Monitor for potential adverse effects: dysgeusia (altered taste) and diarrhea are most common 2
• Watch for hypersensitivity reactions, including anaphylaxis and serious skin reactions 2
• Monitor for hepatotoxicity (hepatic transaminase elevations, clinical hepatitis, and jaundice) 2

Common Pitfalls to Avoid

1. Delayed initiation: Treatment must begin within 5 days of symptom onset for optimal efficacy
2. Missing drug interactions: Failure to thoroughly review concomitant medications
3. Inappropriate dose adjustments: Not adjusting for renal impairment
4. Overlooking contraindications: Using in patients with severe hepatic impairment (Child-Pugh Class C) 2
5. Inappropriate use in low-risk patients: Not recommended for those at low risk of hospitalization 1

The evidence strongly supports nirmatrelvir/ritonavir as the preferred treatment for COVID-19 in high-risk patients due to its significant reduction in hospitalization risk and mortality benefit, with the convenience of oral administration 1, 7.