What adjustments should be made to a patient's medication regimen, which includes quetiapine, acetaminophen, vitamin D, metoprolol, lisinopril, and atorvastatin, when initiating Paxlovid (nirmatrelvir/ritonavir) for COVID-19 treatment?

Medication Adjustments When Initiating Paxlovid in a Patient Taking Quetiapine and Other Medications

When initiating Paxlovid (nirmatrelvir/ritonavir) for COVID-19 treatment in a patient taking quetiapine, acetaminophen, vitamin D, metoprolol, lisinopril, and atorvastatin, the quetiapine dose should be reduced to 1/6 of the current dose, atorvastatin should be temporarily suspended, and metoprolol dose should be reduced with careful monitoring. 1, 2

Drug Interactions with Paxlovid

High-Risk Interactions Requiring Immediate Action

• Quetiapine: Ritonavir significantly increases quetiapine concentrations through CYP3A4 inhibition

  • Reduce quetiapine dose to 1/6 of the current dose during Paxlovid treatment and monitor for quetiapine-associated adverse reactions 1
  • Resume normal dosing 3-5 days after completing Paxlovid 2

• Atorvastatin: Significantly increased risk of myopathy and rhabdomyolysis

  • Temporarily suspend atorvastatin during the 5-day Paxlovid treatment and for 3 days after 1, 3
  • Short-term statin interruption poses minimal cardiovascular risk compared to the risk of severe COVID-19 4

• Metoprolol: Increased beta-blocker exposure may cause bradycardia and hypotension

  • Reduce metoprolol dose by 50% and monitor blood pressure and heart rate closely 1, 4
  • Consider dose adjustment based on clinical response 2

Medications with Minimal or No Significant Interactions

• Acetaminophen: No significant interaction with Paxlovid; can be continued at current dose 3
• Vitamin D: No known significant interaction; can be continued 3
• Lisinopril: Primarily eliminated renally with minimal CYP metabolism; can be continued at current dose 3, 4

Monitoring Recommendations During Paxlovid Treatment

• Monitor for signs of quetiapine toxicity: excessive sedation, orthostatic hypotension, QT prolongation 1, 2
• Check blood pressure and heart rate daily while on reduced metoprolol dose 4
• Monitor for common Paxlovid side effects: dysgeusia (altered taste) and diarrhea 5
• Educate patient to report any new or worsening symptoms immediately 3

Post-Paxlovid Considerations

• Resume normal atorvastatin dosing 3 days after completing Paxlovid course 3, 4
• Gradually return to pre-Paxlovid quetiapine dose over 2-3 days after completing treatment 2
• Return to original metoprolol dose after completing Paxlovid and confirming stable vital signs 4

Important Caveats

• Ritonavir's inhibitory effects on CYP3A4 may persist for several days after discontinuation 5, 3
• The 5-day Paxlovid treatment should be started as early as possible within 5 days of symptom onset for maximum efficacy 5
• Use the Liverpool COVID-19 Drug Interaction Tool for the most up-to-date information on specific drug interactions 5, 3

Remember that the benefits of Paxlovid in reducing COVID-19 progression to severe disease outweigh the manageable risks of temporary medication adjustments in high-risk patients 6, 5.