Before prescribing nirmatrelvir/ritonavir, clinicians should carefully review concomitant medications for drug interactions to reduce the risk of harm.
Drug interaction tools and resources:
Drug classes of particular concern are:
- oral anticoagulants
- neuropsychiatric drugs
Questions to consider:
- Is the patient is taking or has taken a CYP3A4 enzyme inducer in the last 28 days (e.g., certain anticonvulsants, antineoplastics, a rifamycin, St. John’s wort)?
- Do NOT prescribe nirmatrelvir/ ritonavir.
- Is the patient taking an interacting drug with a long plasma half-life and narrow therapeutic window (e.g., certain antiarrhythmics, antipsychotics, antineoplastics), in that the interacting drug will persist in the body after the last dose and may still interact with nirmatrelvir/ritonavir?
- Do NOT prescribe nirmatrelvir/ritonavir, even if the interacting drug can be held.
- Is the patient taking an interacting drug that can be safely held?
- Hold the medication starting the first day of nirmatrelvir/ritonavir therapy and resume 2 to 5 days after the last dose of nirmatrelvir/ritonavir treatment depending on recommendations.
- Is a specialist prescriber or pharmacist able to help adjust the dose or dosing interval, replace the drug with an alternative agent, manage side effects, and guide therapeutic drug monitoring?
- Consult a local specialist or pharmacist for advice and recommendation.
Potential management strategies:
Potential management strategies to facilitate the use of nirmatrelvir/ritonavir may differ depending on the magnitude and significance of the interaction. Options include:
- Dose adjustment of the concomitant medication
- Use of an alternative to the concomitant medication
- Increased monitoring for potential adverse reactions to the concomitant medication
- Temporary withholding of the concomitant medication
These strategies should be considered for the 5-day duration of nirmatrelvir/ritonavir treatment and for at least 2 to 5 days after treatment completion (and for potentially longer if nirmatrelvir/ritonavir is administered with an interacting concomitant medication that has a long half-life).
Please note, the onset of inhibition is RAPID and clinically significant drug-drug interactions may occur despite the short treatment course.