Drug interactions
Fentanyl + Paroxetine
Severity: Major
Fentanyl and Paroxetine: 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 serotonin syndrome has been reported with SSRIs. Paroxetine is also a strong CYP2D6 inhibitor and a weak CYP3A4 inhibitor, although fentanyl is mainly metabolized by CYP3A4, so a pharmacokinetic effect is probably small.
What this interaction means in plain words
Fentanyl and Paroxetine 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; Paroxetine belongs to Central Nervous System.
Why it happens
Additive serotonergic effects causing serotonin syndrome.
What to do
Monitor for agitation, tremor, clonus, hyperthermia and autonomic instability, especially after starting or increasing a dose. Stop the serotonergic drugs and give supportive care if serotonin syndrome is suspected.
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 Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline Contraindicated
Frequently asked questions
Can I take Fentanyl with Paroxetine?
MediHelp rates the interaction as major. Fentanyl and Paroxetine 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 serotonin syndrome has been reported with SSRIs. Paroxetine is also a strong CYP2D6 inhibitor and a weak CYP3A4 inhibitor, although fentanyl is mainly metabolized by CYP3A4, so a pharmacokinetic effect is probably small.
How serious is the interaction between Fentanyl and Paroxetine?
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, clonus, hyperthermia and autonomic instability, especially after starting or increasing a dose. Stop the serotonergic drugs and give supportive care if serotonin syndrome is suspected.
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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