Drug interactions
Methadone + Nefazodone
Severity: Major
Methadone and Nefazodone: major 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
Nefazodone strongly inhibits CYP3A4 and can increase methadone exposure, leading to sedation, respiratory depression and QT prolongation. Nefazodone also has serotonergic activity.
What this interaction means in plain words
Methadone and Nefazodone can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Why it happens
CYP3A4 inhibition by nefazodone reduces methadone clearance, with additional serotonergic effects.
What to do
Avoid if possible and choose an antidepressant with less CYP3A4 inhibition. If combined, monitor for sedation, respiratory depression and QTc and reduce the methadone dose as needed.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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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 Nefazodone?
MediHelp rates the interaction as major. Methadone and Nefazodone can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Nefazodone strongly inhibits CYP3A4 and can increase methadone exposure, leading to sedation, respiratory depression and QT prolongation. Nefazodone also has serotonergic activity.
How serious is the interaction between Methadone and Nefazodone?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid if possible and choose an antidepressant with less CYP3A4 inhibition. If combined, monitor for sedation, respiratory depression and QTc and reduce the methadone dose as needed.
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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