Drug interactions
Fluoxetine + Oxycodone
Severity: Major
Fluoxetine and Oxycodone: major interaction.
Last updated Sources: US FDA label
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 is a strong CYP2D6 inhibitor and can reduce conversion of oxycodone to oxymorphone, altering analgesic effect, although oxycodone itself is also cleared by CYP3A4. Both drugs also carry serotonergic activity, so serotonin syndrome is possible.
What this interaction means in plain words
Fluoxetine and Oxycodone 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.
Fluoxetine belongs to Central Nervous System; Oxycodone belongs to Musculoskeletal.
Why it happens
Pharmacodynamic serotonergic additivity plus CYP2D6 inhibition by fluoxetine altering oxycodone metabolism.
What to do
Monitor for agitation, tremor, hyperreflexia, hyperthermia and diarrhea, especially after dose changes. Reassess analgesic response and titrate oxycodone to effect.
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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References
Other interactions of Oxycodone
- Alvimopan + Oxycodone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Oxycodone Contraindicated
- Isocarboxazid + Oxycodone Contraindicated
- Olanzapine / samidorphan + Oxycodone Contraindicated
- Oxycodone + Phenelzine Contraindicated
- Oxycodone + Sodium oxybate 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 Oxycodone?
MediHelp rates the interaction as major. Fluoxetine and Oxycodone 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. Fluoxetine is a strong CYP2D6 inhibitor and can reduce conversion of oxycodone to oxymorphone, altering analgesic effect, although oxycodone itself is also cleared by CYP3A4. Both drugs also carry serotonergic activity, so serotonin syndrome is possible.
How serious is the interaction between Fluoxetine and Oxycodone?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for agitation, tremor, hyperreflexia, hyperthermia and diarrhea, especially after dose changes. Reassess analgesic response and titrate oxycodone to effect.
What other medicines interact with Oxycodone?
MediHelp also lists interactions of Oxycodone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Isocarboxazid. The full list is on the Oxycodone page.
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