Drug interactions
Fluoxetine + Methadone
Severity: Moderate
Fluoxetine and Methadone: 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
Fluoxetine inhibits CYP2D6 and to some extent CYP3A4 and CYP2B6, which may raise methadone levels, and both drugs can prolong the QT interval. Serotonergic toxicity is also possible but uncommon.
What this interaction means in plain words
Fluoxetine and Methadone 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.
Fluoxetine belongs to Central Nervous System; Methadone belongs to Musculoskeletal.
Why it happens
CYP inhibition by fluoxetine reducing methadone clearance, plus additive QT prolongation and serotonergic effects.
What to do
Monitor for sedation, respiratory depression and QTc prolongation, and adjust methadone dose as needed. Watch for signs of serotonin syndrome.
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
Other interactions of Fluoxetine
- Fluoxetine + Isocarboxazid Contraindicated
- Fluoxetine + Mavacamten Contraindicated
- Fluoxetine + Methylene blue Contraindicated
- Fluoxetine + Phenelzine Contraindicated
- Fluoxetine + Pimozide Contraindicated
- Fluoxetine + Rasagiline Contraindicated
Frequently asked questions
Can I take Fluoxetine with Methadone?
MediHelp rates the interaction as moderate. Fluoxetine and Methadone 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. Fluoxetine inhibits CYP2D6 and to some extent CYP3A4 and CYP2B6, which may raise methadone levels, and both drugs can prolong the QT interval. Serotonergic toxicity is also possible but uncommon.
How serious is the interaction between Fluoxetine and Methadone?
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 sedation, respiratory depression and QTc prolongation, and adjust methadone dose as needed. Watch for signs of serotonin syndrome.
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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