Drug interactions
Hydrocodone + Ketoconazole
Severity: Major
Hydrocodone and Ketoconazole: major 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 is a strong CYP3A4 inhibitor and can substantially increase hydrocodone concentrations. This raises the risk of profound sedation and potentially fatal respiratory depression, and effects may persist after dosing changes.
What this interaction means in plain words
Hydrocodone and Ketoconazole can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Hydrocodone belongs to Musculoskeletal; Ketoconazole belongs to Anti Fungals.
Why it happens
Strong CYP3A4 inhibition reduces hydrocodone metabolism to norhydrocodone, increasing parent drug exposure.
What to do
Avoid the combination if possible, or reduce the hydrocodone dose and monitor closely for respiratory depression and sedation. If ketoconazole is stopped, hydrocodone levels fall, so reassess the dose.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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Other interactions of Hydrocodone
- Alvimopan + Hydrocodone Contraindicated
- Bupropion-naltrexone + Hydrocodone Contraindicated
- Hydrocodone + Isocarboxazid Contraindicated
- Hydrocodone + Olanzapine / samidorphan Contraindicated
- Hydrocodone + Phenelzine Contraindicated
- Alfentanil + Hydrocodone 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 Hydrocodone with Ketoconazole?
MediHelp rates the interaction as major. Hydrocodone and Ketoconazole can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Ketoconazole is a strong CYP3A4 inhibitor and can substantially increase hydrocodone concentrations. This raises the risk of profound sedation and potentially fatal respiratory depression, and effects may persist after dosing changes.
How serious is the interaction between Hydrocodone and Ketoconazole?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid the combination if possible, or reduce the hydrocodone dose and monitor closely for respiratory depression and sedation. If ketoconazole is stopped, hydrocodone levels fall, so reassess the dose.
What other medicines interact with Hydrocodone?
MediHelp also lists interactions of Hydrocodone with, for example, Alvimopan, Bupropion-naltrexone, Isocarboxazid. The full list is on the Hydrocodone page.
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