Is it safe to take Paxlovid (nirmatrelvir and ritonavir) with NyQuil (acetaminophen, dextromethorphan, and doxylamine)?

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Paxlovid and NyQuil: Safety Assessment

Taking Paxlovid (nirmatrelvir/ritonavir) with NyQuil is generally safe, as the individual components of NyQuil do not have clinically significant interactions with Paxlovid that would require avoiding concurrent use.

Drug Interaction Analysis

Acetaminophen Component

  • Acetaminophen is primarily metabolized by glucuronidation and sulfation, not by CYP3A4, so ritonavir's strong CYP3A4 inhibition does not significantly affect acetaminophen levels 1, 2.
  • No dose adjustment of acetaminophen is needed when used with Paxlovid 3.

Dextromethorphan Component

  • Dextromethorphan is metabolized by CYP2D6 (primary) and CYP3A4 (minor pathway) 2.
  • Ritonavir is a weak CYP2D6 inhibitor and strong CYP3A4 inhibitor, which could theoretically increase dextromethorphan levels 1, 2.
  • However, this interaction is not listed among the contraindicated or high-risk medications requiring action with Paxlovid 4, 3.
  • Monitor for increased dextromethorphan effects (drowsiness, dizziness) but continuation is acceptable 1.

Doxylamine Component

  • Doxylamine is an antihistamine with sedative properties that does not undergo significant CYP3A4 metabolism 2.
  • No clinically significant interaction is expected between doxylamine and Paxlovid components 3.

Clinical Recommendations

Patients can take NyQuil during Paxlovid treatment with the following precautions:

  • Use standard NyQuil dosing without adjustment 3.
  • Be aware of potentially enhanced sedation from dextromethorphan, though this is typically mild 1.
  • Avoid exceeding recommended NyQuil doses, as ritonavir could modestly increase dextromethorphan exposure 2.
  • Space dosing if possible (e.g., take Paxlovid in morning and evening, NyQuil at bedtime) to minimize any theoretical interaction 1.

Important Context

The medications that require action with Paxlovid are those heavily dependent on CYP3A4 metabolism with narrow therapeutic windows, including anticoagulants (rivaroxaban, apixaban), antiarrhythmics (amiodarone, flecainide), immunosuppressants (tacrolimus), and certain statins 4, 1. NyQuil components do not fall into these high-risk categories 3.

Unlike the serious interactions seen with medications such as rivaroxaban (2.5-fold increase in levels) or amiodarone (risk of torsades de pointes), NyQuil's components pose minimal risk when used concurrently with Paxlovid 4, 1.

References

Research

Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences.

Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia, 2022

Guideline

Medication Interactions with Paxlovid

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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