Drug interactions
Codeine + Paroxetine
Severity: Moderate
Codeine and Paroxetine: 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
Paroxetine is a potent CYP2D6 inhibitor and blocks the conversion of codeine to morphine, its active metabolite. Analgesia may be reduced or absent, which can lead to undertreated pain and dose escalation. Serotonergic effects of both agents are an additional minor concern.
What this interaction means in plain words
Codeine and Paroxetine 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; Paroxetine belongs to Central Nervous System.
Why it happens
Paroxetine inhibits CYP2D6-mediated O-demethylation of codeine to morphine, reducing formation of the active analgesic.
What to do
Consider an analgesic that does not depend on CYP2D6 activation, such as morphine or a non-opioid, rather than escalating the codeine dose. If both are continued, monitor pain control closely.
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 Codeine
- Alvimopan + Codeine Contraindicated
- Codeine + Isocarboxazid Contraindicated
- Codeine + Olanzapine / samidorphan Contraindicated
- Codeine + Phenelzine Contraindicated
- Codeine + Tranylcypromine Contraindicated
- Alfentanil + Codeine Major
Other interactions of Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline Contraindicated
Frequently asked questions
Can I take Codeine with Paroxetine?
MediHelp rates the interaction as moderate. Codeine and Paroxetine 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. Paroxetine is a potent CYP2D6 inhibitor and blocks the conversion of codeine to morphine, its active metabolite. Analgesia may be reduced or absent, which can lead to undertreated pain and dose escalation. Serotonergic effects of both agents are an additional minor concern.
How serious is the interaction between Codeine and Paroxetine?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Consider an analgesic that does not depend on CYP2D6 activation, such as morphine or a non-opioid, rather than escalating the codeine dose. If both are continued, monitor pain control closely.
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.
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