Codeine and Fluoxetine: Drug Interaction Guide

Quick answer: This combination requires caution. Codeine and Fluoxetine can be used together with adjustments and monitoring.

Interaction severity: Moderate — caution required

How Codeine interacts with Fluoxetine

Fluoxetine inhibits CYP2D6, the enzyme that converts codeine to morphine; reduced morphine formation lowers analgesic effect, while fluoxetine also increases serotonin syndrome risk.

What you should do

Choose an alternative analgesic such as paracetamol or low-dose morphine, or switch to a non-CYP2D6 inhibiting SSRI (citalopram or sertraline).

Key facts

Severity

Moderate — caution required

Mechanism

Fluoxetine inhibits CYP2D6, the enzyme that converts codeine to morphine; reduced morphine formation lowers analgesic ef...

Action

Choose an alternative analgesic such as paracetamol or low-dose morphine, or switch to a non-CYP2D6 inhibiting SSRI (cit...

Important medical disclaimer: This page provides educational information about drug interactions for general reference. It is not a substitute for professional medical advice, diagnosis, or treatment. Always discuss your specific medications with a qualified healthcare provider before starting, stopping, or changing any treatment. About our editorial team.

Frequently asked questions

Can I take Codeine and Fluoxetine together?

With caution. Choose an alternative analgesic such as paracetamol or low-dose morphine, or switch to a non-CYP2D6 inhibiting SSRI (citalopram or sertraline).

What is the severity of this interaction?

The interaction between Codeine and Fluoxetine is classified as Moderate — caution required. Fluoxetine inhibits CYP2D6, the enzyme that converts codeine to morphine; reduced morphine formation lowers analgesic effect, while fluoxetine also increases serotonin syndrome risk.

What should I do if I'm prescribed both?

Choose an alternative analgesic such as paracetamol or low-dose morphine, or switch to a non-CYP2D6 inhibiting SSRI (citalopram or sertraline). Always consult your prescribing clinician — do not stop or change medications without medical guidance.

Last reviewed: by iMedic Medical Editorial Team. Our editorial process.