What medications to prescribe for COVID-19?

Medications for COVID-19: Evidence-Based Treatment Recommendations

For patients with COVID-19, nirmatrelvir-ritonavir (Paxlovid) is the first-line treatment for high-risk patients within 5 days of symptom onset, with remdesivir as an alternative when Paxlovid is contraindicated. 1, 2

Treatment Algorithm Based on Disease Severity and Risk Factors

Non-Hospitalized Patients with Mild-to-Moderate COVID-19

High-Risk Patients (within 5 days of symptom onset)

1. First-line: Nirmatrelvir-ritonavir (Paxlovid)

   • Standard dosing: 300 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 1
   • For moderate renal impairment (eGFR 30-59 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 1
   • For severe renal impairment (eGFR <30 mL/min): 300 mg nirmatrelvir with 100 mg ritonavir once on day 1, then 150 mg nirmatrelvir with 100 mg ritonavir once daily for days 2-5 1

2. If Paxlovid is contraindicated:

   • Remdesivir IV (200 mg on day 1, then 100 mg daily for 2 additional days) 3, 2
   • Molnupiravir (800 mg twice daily for 5 days) - only when other options unavailable 2

Low-Risk Patients

• Symptomatic management with acetaminophen for fever 4
• Maintain hydration 4
• Monitor for disease progression

Hospitalized Patients with Moderate-to-Severe COVID-19

1. Oxygen therapy for hypoxemic patients (SpO2 <94%) 5
2. Dexamethasone for patients requiring oxygen (decreases mortality in severe/critical cases) 5, 6
3. Remdesivir for patients requiring supplemental oxygen 3, 6
4. Anticoagulation - thromboprophylaxis with low-molecular-weight heparin 5
5. Consider IL-6 inhibitors for patients with severe inflammatory response 2, 6

Important Considerations and Potential Pitfalls

Drug Interactions with Nirmatrelvir-ritonavir

• Ritonavir is a strong CYP3A4 inhibitor that may lead to significant drug interactions 1
• Critical warning: Review all medications before prescribing Paxlovid to assess potential drug-drug interactions 1
• Interactions may persist for several days after completing treatment 7

Timing of Treatment

• Antiviral treatments are most effective when initiated early (within 5 days of symptom onset) 1, 8
• Delayed treatment significantly reduces efficacy of antivirals

Monitoring

• For patients on remdesivir: Monitor liver function tests before and during treatment 3
• For patients on dexamethasone: Monitor for hyperglycemia and secondary infections

Ineffective Treatments to Avoid

• Hydroxychloroquine - no proven benefit for COVID-19 treatment 2
• Ivermectin - not recommended based on current evidence 8
• Azithromycin - not recommended for COVID-19 treatment 8
• Lopinavir-ritonavir - insufficient evidence of benefit 2

Special Populations

Immunocompromised Patients

• May require longer treatment courses
• Higher priority for early antiviral therapy 7
• Consider combination therapy in severe cases

Patients with Rheumatic Diseases

• NSAIDs, hydroxychloroquine, and colchicine may be continued if necessary to control underlying disease 2
• For patients with symptomatic COVID-19, conventional DMARDs, biologics (except IL-1 and IL-6 inhibitors), and JAK inhibitors should be temporarily withheld 2
• IL-1 and IL-6 inhibitors may be continued if necessary to control underlying disease 2

Patients with Inflammatory Bowel Disease

• Glucocorticoids should be continued at the lowest effective dose to control underlying disease and avoid adrenal insufficiency 2
• Anti-TNF therapy, anti-IL-12/23p40 therapy, and anti-α4β7 integrin therapy can be continued 2

Follow-up and Recovery

• Schedule virtual follow-up 1-2 weeks after diagnosis 7
• Consider treatment escalation if clinical deterioration occurs
• For patients who received immunosuppressants, biologics, or JAK inhibitors that were withheld, consider restarting 7-14 days after symptom resolution 2

Remember that treatment recommendations continue to evolve as new evidence emerges, and the most recent guidelines should be consulted for up-to-date information.