Drug interactions
Dextromethorphan + Fluoxetine
Severity: Major
Dextromethorphan and Fluoxetine: 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 strongly inhibits CYP2D6, markedly raising dextromethorphan exposure, and both drugs are serotonergic. This increases the risk of serotonin syndrome and dextromethorphan toxicity.
What this interaction means in plain words
Dextromethorphan 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.
Dextromethorphan belongs to Respiratory; Fluoxetine belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by fluoxetine reduces dextromethorphan clearance, combined with additive serotonergic effects.
What to do
Avoid the combination and use a non-serotonergic antitussive. If dextromethorphan is required, use the lowest dose and monitor for serotonin toxicity; the inhibitory effect persists for weeks after fluoxetine is stopped.
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 Dextromethorphan
- Dextromethorphan + Isocarboxazid Contraindicated
- Dextromethorphan + Linezolid Contraindicated
- Dextromethorphan + Phenelzine Contraindicated
- Dextromethorphan + Rasagiline Contraindicated
- Dextromethorphan + Safinamide Contraindicated
- Dextromethorphan + Selegiline 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 Dextromethorphan with Fluoxetine?
MediHelp rates the interaction as major. Dextromethorphan 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 strongly inhibits CYP2D6, markedly raising dextromethorphan exposure, and both drugs are serotonergic. This increases the risk of serotonin syndrome and dextromethorphan toxicity.
How serious is the interaction between Dextromethorphan 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: Avoid the combination and use a non-serotonergic antitussive. If dextromethorphan is required, use the lowest dose and monitor for serotonin toxicity; the inhibitory effect persists for weeks after fluoxetine is stopped.
What other medicines interact with Dextromethorphan?
MediHelp also lists interactions of Dextromethorphan with, for example, Isocarboxazid, Linezolid, Phenelzine. The full list is on the Dextromethorphan page.
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