Drug interactions
Methadone + Nirmatrelvir / ritonavir
Severity: Moderate
Methadone and Nirmatrelvir / ritonavir: moderate interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Ritonavir can lower methadone concentrations through induction of CYP2B6 and other pathways, partly offset by CYP3A4 inhibition. Patients may experience withdrawal or loss of effect, and occasionally excess opioid effect. The short five-day treatment course limits the exposure period.
What this interaction means in plain words
Methadone and Nirmatrelvir / ritonavir can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Why it happens
Ritonavir induces CYP2B6 and other enzymes while inhibiting CYP3A4, producing variable changes in methadone clearance.
What to do
Monitor for withdrawal and oversedation during and shortly after the course, adjusting methadone only if clinically required. Do not stop methadone empirically.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Methadone
- Alvimopan + Methadone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Methadone Contraindicated
- Droperidol + Methadone Contraindicated
- Ibutilide + Methadone Contraindicated
- Isocarboxazid + Methadone Contraindicated
- Lefamulin + Methadone Contraindicated
Frequently asked questions
Can I take Methadone with Nirmatrelvir / ritonavir?
MediHelp rates the interaction as moderate. Methadone and Nirmatrelvir / ritonavir can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Ritonavir can lower methadone concentrations through induction of CYP2B6 and other pathways, partly offset by CYP3A4 inhibition. Patients may experience withdrawal or loss of effect, and occasionally excess opioid effect. The short five-day treatment course limits the exposure period.
How serious is the interaction between Methadone and Nirmatrelvir / ritonavir?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for withdrawal and oversedation during and shortly after the course, adjusting methadone only if clinically required. Do not stop methadone empirically.
What other medicines interact with Methadone?
MediHelp also lists interactions of Methadone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Droperidol. The full list is on the Methadone page.
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