Drug interactions
Fluoxetine + Promethazine
Severity: Moderate
Fluoxetine and Promethazine: moderate 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 is a strong CYP2D6 inhibitor and promethazine is partly metabolized by CYP2D6, so promethazine exposure may rise. This can increase sedation, anticholinergic effects and QT-related risk. Fluoxetine itself can also prolong QT at times.
What this interaction means in plain words
Fluoxetine and Promethazine can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Fluoxetine belongs to Central Nervous System; Promethazine belongs to Respiratory.
Why it happens
Inhibition of CYP2D6-mediated promethazine metabolism by fluoxetine, plus additive QT effects.
What to do
Monitor for excess sedation, anticholinergic effects and palpitations, and use the lowest effective promethazine dose. Consider an alternative antihistamine or antiemetic if QT risk factors are present.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Promethazine
- Cabergoline + Promethazine Contraindicated
- Dopamine + Promethazine Contraindicated
- Ibutilide + Promethazine Contraindicated
- Pimozide + Promethazine Contraindicated
- Promethazine + Thioridazine Contraindicated
- Alfentanil + Promethazine 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 Fluoxetine with Promethazine?
MediHelp rates the interaction as moderate. Fluoxetine and Promethazine can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Fluoxetine is a strong CYP2D6 inhibitor and promethazine is partly metabolized by CYP2D6, so promethazine exposure may rise. This can increase sedation, anticholinergic effects and QT-related risk. Fluoxetine itself can also prolong QT at times.
How serious is the interaction between Fluoxetine and Promethazine?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for excess sedation, anticholinergic effects and palpitations, and use the lowest effective promethazine dose. Consider an alternative antihistamine or antiemetic if QT risk factors are present.
What other medicines interact with Promethazine?
MediHelp also lists interactions of Promethazine with, for example, Cabergoline, Dopamine, Ibutilide. The full list is on the Promethazine page.
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