Is Paxlovid (nirmatrelvir/ritonavir) safe to use with Ajovy (fremanezumab), Quetiapine, Nurtec (rimegepant), Ubrelvy (ubrogepant), Alprazolam, Amitriptyline, and Atorvastatin?

Paxlovid Drug Interactions with Ajovy, Quetiapine, Nurtec, Ubrelvy, Alprazolam, Amitriptyline, and Atorvastatin

Paxlovid should not be administered with this medication regimen due to significant drug interactions, particularly with quetiapine, ubrogepant (Ubrelvy), alprazolam, and atorvastatin, which could lead to serious adverse effects or toxicity.

Critical Drug Interactions

Quetiapine

• Quetiapine is primarily metabolized by CYP3A4, and ritonavir (in Paxlovid) is a strong CYP3A4 inhibitor 1
• Co-administration can lead to significantly increased quetiapine levels, potentially causing serious adverse effects including sedation, hypotension, and QT prolongation 2
• The FDA label specifically mentions antipsychotics like lurasidone and pimozide as contraindicated; while quetiapine is not specifically listed, it has similar metabolism concerns 3

Ubrogepant (Ubrelvy)

• Ubrogepant is specifically listed as contraindicated with Paxlovid in the FDA label 3
• Co-administration can lead to significantly increased ubrogepant concentrations, increasing the risk of adverse effects 3

Alprazolam

• Alprazolam is metabolized by CYP3A4, and ritonavir can significantly increase its plasma concentrations
• This can lead to excessive sedation and respiratory depression
• The FDA label lists "sedative/hypnotics" including triazolam and oral midazolam as contraindicated; alprazolam has similar concerns 3

Atorvastatin

• Atorvastatin levels can increase significantly when co-administered with Paxlovid
• This increases the risk of myopathy and rhabdomyolysis
• The American College of Cardiology recommends temporary discontinuation or significant dose reduction of statins during Paxlovid treatment 1

Other Medications in the Regimen

Fremanezumab (Ajovy)

• Fremanezumab is a monoclonal antibody that is not metabolized by CYP enzymes
• No significant interaction with Paxlovid is expected

Rimegepant (Nurtec)

• Rimegepant is a CGRP receptor antagonist similar to ubrogepant
• While not specifically listed in the FDA label, it likely has similar metabolism concerns as ubrogepant, which is contraindicated 3

Amitriptyline

• Amitriptyline is metabolized by CYP2D6 and CYP3A4
• Co-administration with Paxlovid may increase amitriptyline levels
• This could potentially increase the risk of QT prolongation, anticholinergic effects, and serotonin syndrome

Management Recommendations

1. Avoid Paxlovid in this patient due to multiple significant drug interactions

2. Alternative COVID-19 treatment options should be considered:

   • Molnupiravir
   • Monoclonal antibody treatments (if appropriate variants are circulating)
   • Remdesivir (if IV administration is feasible)

3. If Paxlovid is absolutely necessary:

   • Temporarily discontinue quetiapine, Ubrelvy, alprazolam, and atorvastatin
   • Consider alternative medications for these conditions during the 5-day Paxlovid course
   • Resume original medications at least 3 days after completing Paxlovid (due to the washout period)

Important Considerations

• The ritonavir component of Paxlovid is a potent inhibitor of CYP3A4, affecting the metabolism of approximately 60% of available medications 4
• Drug interactions can range from reduced therapeutic efficacy to potentially life-threatening toxicities 2
• Careful monitoring and close collaboration between healthcare providers is essential if any of these medications must be continued during Paxlovid treatment

The complexity and severity of these drug interactions highlight the importance of a thorough medication review before prescribing Paxlovid, especially in patients on multiple medications.