Drug interactions
Codeine + Ketoconazole
Severity: Minor
Codeine and Ketoconazole: minor 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
Ketoconazole inhibits CYP3A4, and strongly so, while codeine is mainly activated by CYP2D6. Blocking CYP3A4 diverts codeine toward more norcodeine formation and may modestly alter morphine exposure, so the net clinical effect is small and unpredictable. Ketoconazole is not a significant CYP2D6 inhibitor.
What this interaction means in plain words
Codeine and Ketoconazole have a small, usually unimportant interaction. Most people can take both; the pharmacist may still mention it so that any unexpected effect is recognised.
Codeine belongs to Musculoskeletal; Ketoconazole belongs to Anti Fungals.
Why it happens
CYP3A4 inhibition alters the codeine metabolic pathway to norcodeine, with minor effect on morphine formation.
What to do
No routine dose change is needed; monitor analgesic response and sedation.
What to ask your pharmacist
- Is there anything I should notice while taking both?
- Do I need to tell my doctor at the next visit?
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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 Ketoconazole
- Alfuzosin + Ketoconazole Contraindicated
- Alprazolam + Ketoconazole Contraindicated
- Avanafil + Ketoconazole Contraindicated
- Conivaptan + Ketoconazole Contraindicated
- Dihydroergotamine intranasal + Ketoconazole Contraindicated
- Dihydroergotamine + Ketoconazole Contraindicated
Frequently asked questions
Can I take Codeine with Ketoconazole?
MediHelp rates the interaction as minor. Codeine and Ketoconazole have a small, usually unimportant interaction. Most people can take both; the pharmacist may still mention it so that any unexpected effect is recognised. Ketoconazole inhibits CYP3A4, and strongly so, while codeine is mainly activated by CYP2D6. Blocking CYP3A4 diverts codeine toward more norcodeine formation and may modestly alter morphine exposure, so the net clinical effect is small and unpredictable. Ketoconazole is not a significant CYP2D6 inhibitor.
How serious is the interaction between Codeine and Ketoconazole?
MediHelp rates it minor, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: No routine dose change is needed; monitor analgesic response and sedation.
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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