Is Paxlovid (nirmatrelvir and ritonavir) being used to treat Coronavirus disease 2019 (Covid-19) in patients with impaired renal function or those at high risk of severe illness, such as adults 50 years or older with underlying health conditions?

Is Paxlovid Currently Used to Treat COVID-19?

Yes, Paxlovid (nirmatrelvir/ritonavir) is currently the first-line treatment for COVID-19 in adults with mild-to-moderate disease who are at high risk for progression to severe illness, including hospitalization or death. 1, 2, 3

Current FDA Approval and Indications

Paxlovid is FDA-approved for treating mild-to-moderate COVID-19 in adults at high risk for progression to severe disease. 3 The medication must be initiated within 5 days of symptom onset to be effective. 1, 2, 3

Paxlovid is NOT approved for pre-exposure or post-exposure prophylaxis for COVID-19 prevention. 3

Who Should Receive Paxlovid

High-Risk Patients (Strong Recommendation)

The World Health Organization and American College of Physicians strongly recommend Paxlovid for patients with: 4, 1, 2

• Unvaccinated status 1
• Age ≥65 years 2
• Immunosuppression 2
• Multiple comorbidities (≥3) 2
• Radiographic evidence of pneumonia 1
• Hematological disease 2

Moderate-Risk Patients (Conditional Recommendation)

For patients with non-severe COVID-19 at moderate risk of hospitalization, the WHO suggests using Paxlovid, though this is a conditional recommendation due to smaller absolute benefits compared to high-risk patients. 4

Low-Risk Patients (Recommendation Against)

The WHO recommends against using Paxlovid in low-risk patients with non-severe COVID-19, as any benefits are trivial and do not justify the risks of drug interactions and adverse effects. 4, 1, 2

Real-World Effectiveness Data

Recent large-scale studies demonstrate Paxlovid's continued effectiveness:

• 39% relative risk reduction in hospitalization 1, 5
• 61% relative risk reduction in death 1, 5
• Benefits observed in both vaccinated and unvaccinated patients 1, 5
• Remains effective against Omicron subvariants through August 2023 1, 5

Among 5,287 patients treated with Paxlovid, less than 1% experienced COVID-19-related hospitalization or emergency department encounters during days 5-15 after treatment. 6

Critical Prescribing Requirements

Mandatory Drug Interaction Review

Before prescribing Paxlovid, you MUST conduct a thorough medication review using a drug interaction checker. 1, 2, 3, 7 Ritonavir is a potent CYP3A4 inhibitor that can cause potentially life-threatening drug interactions. 3, 7

The FDA includes a boxed warning stating that ritonavir may lead to greater exposure of certain concomitant medications, resulting in potentially severe, life-threatening, or fatal events. 3

Dosing Adjustments for Renal Impairment

Standard dosing requires adjustment based on kidney function: 3

• Normal renal function (eGFR ≥60): 300 mg nirmatrelvir + 100 mg ritonavir twice daily for 5 days
• Moderate impairment (eGFR 30-59): 150 mg nirmatrelvir + 100 mg ritonavir twice daily for 5 days
• Severe impairment (eGFR <30) or hemodialysis: 300 mg nirmatrelvir + 100 mg ritonavir once on day 1, then 150 mg nirmatrelvir + 100 mg ritonavir once daily on days 2-5 (after dialysis on dialysis days)

Contraindications

Paxlovid is contraindicated in: 3

• History of clinically significant hypersensitivity to nirmatrelvir or ritonavir
• Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations cause serious/life-threatening reactions
• Co-administration with potent CYP3A inducers

Paxlovid is not recommended in severe hepatic impairment (Child-Pugh Class C). 3

Alternative Treatments When Paxlovid Is Unavailable or Contraindicated

Remdesivir

Remdesivir is the preferred alternative, particularly for: 4, 1

• Patients with problematic drug interactions with ritonavir
• Pregnant patients
• Children (due to mutagenesis concerns with molnupiravir)

The WHO notes remdesivir requires a 3-day IV course, making it less practical than oral Paxlovid. 1

Molnupiravir

Molnupiravir is a less effective oral alternative when Paxlovid is unavailable or contraindicated. 4, 1, 2 The WHO indicates Paxlovid is superior to molnupiravir based on greater reduction in hospitalization. 1

Special Populations

Pregnant and Breastfeeding Patients

Pregnant and breastfeeding patients may consider Paxlovid use through shared decision-making about potential risks versus benefits. 1 However, remdesivir may be preferred in this population. 1

Older Adults

Patients older than 65 years have significantly higher plasma trough concentrations of nirmatrelvir and ritonavir, with an 11.2-fold increased odds of achieving excessive plasma levels compared to younger patients. 8 Despite this, older adults derive substantial benefit from treatment, with greater absolute risk reduction for hospitalization. 5

Common Pitfalls to Avoid

• Do not prescribe beyond 5 days of symptom onset - effectiveness significantly decreases with delayed treatment 1, 2
• Do not skip the drug interaction review - this is mandatory and potentially life-saving 1, 2, 3
• Do not use in low-risk patients - risks outweigh trivial benefits 4, 1
• Do not combine with other antivirals - there is no evidence supporting combination therapy 4

Monitoring During Treatment

Monitor for: 1, 2

• Hypersensitivity reactions (including anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis) 3
• Hepatic function if baseline abnormalities are present 1, 2, 3
• Ensure patient continues isolation per public health recommendations 1, 2

Long COVID Considerations

Emerging evidence suggests Paxlovid may have a role in long COVID: 4

• A case report noted resolution of long COVID following Paxlovid treatment
• A study investigating acute COVID-19 treatment with Paxlovid showed a 25% reduction in long COVID incidence
• Further investigation is warranted for both prevention and treatment of long COVID