Drug interactions
Codeine + Fluoxetine
Severity: Moderate
Codeine and Fluoxetine: 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 potent CYP2D6 inhibitor and can markedly reduce conversion of codeine to morphine, leading to diminished pain relief. Additive serotonergic effects are also possible.
What this interaction means in plain words
Codeine and Fluoxetine 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.
Codeine belongs to Musculoskeletal; Fluoxetine belongs to Central Nervous System.
Why it happens
Strong CYP2D6 inhibition by fluoxetine and norfluoxetine reduces formation of morphine from codeine.
What to do
Choose an analgesic not reliant on CYP2D6, such as morphine at an appropriate dose, if opioid therapy is needed. Monitor for serotonin toxicity.
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?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Codeine and Fluoxetine, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 7 days on the web. No card needed.
Other interactions of Codeine
- Alvimopan + Codeine Contraindicated
- Codeine + Isocarboxazid Contraindicated
- Codeine + Olanzapine / samidorphan Contraindicated
- Codeine + Phenelzine Contraindicated
- Codeine + Tranylcypromine Contraindicated
- Alfentanil + Codeine 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 Codeine with Fluoxetine?
MediHelp rates the interaction as moderate. Codeine and Fluoxetine 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 potent CYP2D6 inhibitor and can markedly reduce conversion of codeine to morphine, leading to diminished pain relief. Additive serotonergic effects are also possible.
How serious is the interaction between Codeine and Fluoxetine?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Choose an analgesic not reliant on CYP2D6, such as morphine at an appropriate dose, if opioid therapy is needed. Monitor for serotonin toxicity.
What other medicines interact with Codeine?
MediHelp also lists interactions of Codeine with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Codeine page.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
