Drug interactions
Fentanyl intranasal + Fluoxetine
Severity: Major
Fentanyl intranasal 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
Fentanyl has serotonergic activity, and with fluoxetine it can contribute to serotonin syndrome. Fluoxetine may also modestly raise fentanyl exposure through CYP3A4 inhibition, prolonging opioid effects.
What this interaction means in plain words
Fentanyl intranasal 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.
Why it happens
Additive serotonergic activity, with possible CYP3A4 inhibition raising fentanyl levels.
What to do
Monitor for agitation, clonus, hyperthermia and autonomic instability, and for respiratory depression. Use the lowest effective fentanyl dose or an alternative opioid with less serotonergic activity.
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 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 intranasal with Fluoxetine?
MediHelp rates the interaction as major. Fentanyl intranasal 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 has serotonergic activity, and with fluoxetine it can contribute to serotonin syndrome. Fluoxetine may also modestly raise fentanyl exposure through CYP3A4 inhibition, prolonging opioid effects.
How serious is the interaction between Fentanyl intranasal 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, clonus, hyperthermia and autonomic instability, and for respiratory depression. Use the lowest effective fentanyl dose or an alternative opioid with less serotonergic activity.
What other medicines interact with Fluoxetine?
MediHelp also lists interactions of Fluoxetine with, for example, Isocarboxazid, Mavacamten, Methylene blue. The full list is on the Fluoxetine page.
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