Drug interactions
Fentanyl + Fluoxetine
Severity: Major
Fentanyl and Fluoxetine: 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
Fluoxetine combined with fentanyl may precipitate serotonin syndrome, although this is uncommon. Fluoxetine also inhibits CYP2D6 and weakly CYP3A4, which may modestly alter opioid exposure.
What this interaction means in plain words
Fentanyl and Fluoxetine 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.
Fentanyl belongs to Musculoskeletal; Fluoxetine belongs to Central Nervous System.
Why it happens
Additive serotonergic effects from SSRI reuptake inhibition and fentanyl serotonergic activity, with possible minor CYP3A4 inhibition.
What to do
Monitor for agitation, tremor, hyperreflexia, clonus and fever, especially when starting or increasing doses. Stop the serotonergic drugs and give supportive care if serotonin syndrome develops.
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 Fentanyl
- Alvimopan + Fentanyl Contraindicated
- Fentanyl + Isocarboxazid Contraindicated
- Fentanyl + Olanzapine / samidorphan Contraindicated
- Fentanyl + Phenelzine Contraindicated
- Fentanyl + Tranylcypromine Contraindicated
- Alfentanil + Fentanyl Major
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 Fentanyl with Fluoxetine?
MediHelp rates the interaction as major. Fentanyl and Fluoxetine 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 combined with fentanyl may precipitate serotonin syndrome, although this is uncommon. Fluoxetine also inhibits CYP2D6 and weakly CYP3A4, which may modestly alter opioid exposure.
How serious is the interaction between Fentanyl and Fluoxetine?
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, clonus and fever, especially when starting or increasing doses. Stop the serotonergic drugs and give supportive care if serotonin syndrome develops.
What other medicines interact with Fentanyl?
MediHelp also lists interactions of Fentanyl with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Fentanyl page.
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