Is Paxlovid (nirmatrelvir/ritonavir) contraindicated in elderly patients with impaired renal function?

Paxlovid in Elderly Patients with Impaired Renal Function

Paxlovid is not contraindicated in elderly patients, but requires dose adjustment in those with impaired renal function based on the severity of renal impairment. 1

Dosing Considerations in Elderly Patients

Paxlovid (nirmatrelvir/ritonavir) can be safely used in elderly patients with appropriate dose adjustments based on renal function. The FDA-approved labeling provides specific guidance:

• Normal renal function or mild impairment (eGFR ≥60 mL/min): Standard dose of 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir twice daily for 5 days 1
• Moderate renal impairment (eGFR ≥30 to <60 mL/min): Reduced dose of 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir twice daily for 5 days 1
• Severe renal impairment (eGFR <30 mL/min): First day: 300 mg nirmatrelvir with 100 mg ritonavir once; Days 2-5: 150 mg nirmatrelvir with 100 mg ritonavir once daily 1

Safety Profile in Elderly Population

Clinical studies of Paxlovid included subjects 65 years of age and older (10% of the integrated dataset), with 2% being 75 years of age and older. No overall differences in safety were observed between elderly subjects and younger subjects, although greater sensitivity in some older individuals cannot be ruled out 1.

Pharmacokinetic Considerations

Renal impairment increases nirmatrelvir exposure, which may increase the risk of adverse reactions. A phase I study demonstrated that systemic nirmatrelvir exposure increased with increasing renal impairment:

• Mild renal impairment: 24% increase in exposure
• Moderate renal impairment: 87% increase in exposure
• Severe renal impairment: 204% increase in exposure 2

This is why dose adjustments are crucial in elderly patients with renal impairment.

Drug Interactions in Elderly Patients

Elderly patients often take multiple medications, making drug interactions a significant concern with Paxlovid:

1. Ritonavir is a strong CYP3A inhibitor that can increase concentrations of drugs metabolized by CYP3A 1
2. Some medications commonly used in elderly patients may be contraindicated with Paxlovid, including:
   • Amiodarone 3
   • Certain statins (lovastatin, simvastatin) 3
   • Some antiarrhythmics 3

Clinical Evidence in Elderly Patients

A case report of a 79-year-old female with moderate COVID-19 caused by Omicron variant BA.2.0 showed improvement in symptoms (xerostomia, cough, fever) after three days of Paxlovid treatment. Laboratory markers normalized, and chest CT showed absorption of lesions 4.

Potential Complications to Monitor

1. Renal function deterioration: Monitor renal function throughout treatment, especially in elderly patients with baseline renal impairment 1
2. Drug-drug interactions: Ritonavir can significantly affect the metabolism of many medications commonly used in elderly patients 5
3. Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir 1

Common Pitfalls and How to Avoid Them

1. Failure to adjust dose based on renal function: Always calculate eGFR before prescribing Paxlovid to elderly patients
2. Overlooking drug interactions: Review all medications the patient is taking before prescribing Paxlovid
3. Not monitoring renal function: Regular monitoring of renal function during treatment is essential
4. Inappropriate use in severe hepatic impairment: Paxlovid is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 1

In conclusion, while Paxlovid is not contraindicated in elderly patients, careful consideration of renal function, appropriate dose adjustments, and vigilant monitoring for drug interactions are essential for safe and effective use in this population.