Who should be prescribed Paxlovid (nirmatrelvir/ritonavir) for treatment of COVID-19?

Who Should Get Paxlovid

Paxlovid should be prescribed to adults with confirmed mild-to-moderate COVID-19 who are at high risk for progression to severe disease, initiated within 5 days of symptom onset. 1, 2, 3

High-Risk Patients Who Should Receive Paxlovid

The following populations qualify as high-risk and should be offered Paxlovid treatment:

• Unvaccinated patients are a primary indication for treatment 1
• Age ≥65 years represents a high-risk category, with greater absolute risk reduction in this age group 1, 4
• Immunosuppressed or immunocompromised patients, including organ transplant recipients, should receive Paxlovid 2, 5
• Patients with hematological malignancies or history of hematopoietic cell transplantation should be prescribed Paxlovid 2, 5
• Patients with multiple comorbidities or underlying medical conditions that increase risk for severe COVID-19 should receive treatment 5, 6
• Radiographic evidence of pneumonia (such as patchy opacities in bilateral lung fields) indicates progression beyond upper respiratory infection and supports Paxlovid use 1

Moderate-Risk Patients: Conditional Recommendation

• Patients at moderate risk of hospitalization may be considered for Paxlovid, though this is a weaker recommendation due to smaller absolute benefits compared to high-risk patients 7
• The World Health Organization suggests treatment for this group, but acknowledges uncertainty regarding baseline risk estimates and patient preferences 7

Patients Who Should NOT Receive Paxlovid

Low-risk patients without risk factors for severe disease should not receive Paxlovid, as the potential risks of drug interactions and adverse effects outweigh trivial benefits in this population 7, 1, 5:

• The WHO recommends against using Paxlovid in low-risk patients with non-severe COVID-19, as any benefits are trivial 7, 1
• The absolute benefits in terms of hospitalization prevention are negligible in low-risk populations 1

Critical Timing and Administration Requirements

• Treatment must be initiated within 5 days of symptom onset to be effective, as delaying beyond this window significantly reduces effectiveness 1, 2, 3
• The standard dosing is 300 mg nirmatrelvir with 100 mg ritonavir taken orally twice daily for 5 days 2, 3
• Treatment can be administered with or without food and should be taken at approximately the same time each day 1, 2

Absolute Contraindications

Before prescribing, verify the patient does not have:

• History of clinically significant hypersensitivity to nirmatrelvir or ritonavir 2, 3
• eGFR <30 mL/min (requires dose adjustment; see below) 2, 3
• ALT ≥5 times upper limit of normal 2, 3
• Severe hepatic impairment (Child-Pugh Class C) 3
• Concomitant use of medications highly dependent on CYP3A for clearance where elevated concentrations cause serious/life-threatening reactions 3

Dose Adjustments for Renal Impairment

• Moderate renal impairment (eGFR 30-60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 3
• 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 on Days 2-5 3

Critical Drug Interaction Assessment

A thorough medication review is mandatory before prescribing, as ritonavir is a strong CYP3A inhibitor that can cause potentially severe, life-threatening, or fatal drug interactions 1, 2, 3:

• Review all medications to assess potential interactions with ritonavir 3
• Determine if concomitant medications require dose adjustment, interruption, or additional monitoring 3
• Consider whether the benefit of reducing hospitalization and death outweighs the risk of drug interactions for each individual patient 3

Alternative Therapies When Paxlovid Is Contraindicated

• Remdesivir is the preferred alternative, particularly for patients with problematic drug interactions with ritonavir, pregnant patients, and children 1, 2
• Molnupiravir is a less effective oral alternative when Paxlovid is unavailable or contraindicated, with Paxlovid demonstrating superior reduction in hospitalization 7, 1

Real-World Effectiveness Data

• Paxlovid demonstrates a 39% relative risk reduction in hospitalization and 61% relative risk reduction in death in real-world settings 4
• Benefits are observed in both vaccinated and unvaccinated patients, though absolute risk reduction for hospitalization is greater among patients aged ≥65 years 4
• Paxlovid remains effective against Omicron subvariants through August 2023 1

Common Pitfalls to Avoid

• Do not delay treatment beyond 5 days of symptom onset, as effectiveness drops significantly 1, 2
• Do not prescribe to low-risk patients without risk factors, as harms outweigh benefits 7, 1
• Do not skip the medication reconciliation for drug interactions, as this can lead to serious adverse events 3
• Do not use as pre-exposure or post-exposure prophylaxis, as this is not an approved indication 3