Drug interactions
Benzhydrocodone / acetaminophen + Fluoxetine
Severity: Major
Benzhydrocodone / acetaminophen 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
Benzhydrocodone is a prodrug of hydrocodone, and opioids combined with SSRIs have been linked to serotonin syndrome. Fluoxetine also inhibits CYP2D6, which may alter hydrocodone activation and effect, and additive CNS depression can occur.
What this interaction means in plain words
Benzhydrocodone / acetaminophen 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 plus CYP2D6 inhibition by fluoxetine affecting opioid metabolism.
What to do
Monitor for agitation, tremor, hyperthermia, clonus and diarrhea, especially at initiation and after dose changes. Stop the opioid or serotonergic drug and treat 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 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 Benzhydrocodone / acetaminophen with Fluoxetine?
MediHelp rates the interaction as major. Benzhydrocodone / acetaminophen 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. Benzhydrocodone is a prodrug of hydrocodone, and opioids combined with SSRIs have been linked to serotonin syndrome. Fluoxetine also inhibits CYP2D6, which may alter hydrocodone activation and effect, and additive CNS depression can occur.
How serious is the interaction between Benzhydrocodone / acetaminophen 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, hyperthermia, clonus and diarrhea, especially at initiation and after dose changes. Stop the opioid or serotonergic drug and treat if serotonin syndrome is suspected.
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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