Drug interactions
Fentanyl + Ketoconazole
Severity: Major
Fentanyl 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 markedly raise fentanyl concentrations. This may cause profound sedation and potentially fatal respiratory depression, which can be delayed and prolonged.
What this interaction means in plain words
Fentanyl 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.
Fentanyl belongs to Musculoskeletal; Ketoconazole belongs to Anti Fungals.
Why it happens
Strong inhibition of CYP3A4-mediated fentanyl metabolism by ketoconazole.
What to do
Avoid the combination where possible, or reduce the fentanyl dose and monitor closely for respiratory depression and sedation. Continue monitoring after ketoconazole is stopped, since effects persist.
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 Fentanyl
- Alvimopan + Fentanyl Contraindicated
- Fentanyl + Isocarboxazid Contraindicated
- Fentanyl + Olanzapine / samidorphan Contraindicated
- Fentanyl + Phenelzine Contraindicated
- Fentanyl + Tranylcypromine Contraindicated
- Alfentanil + Fentanyl 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 Fentanyl with Ketoconazole?
MediHelp rates the interaction as major. Fentanyl 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 markedly raise fentanyl concentrations. This may cause profound sedation and potentially fatal respiratory depression, which can be delayed and prolonged.
How serious is the interaction between Fentanyl 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 where possible, or reduce the fentanyl dose and monitor closely for respiratory depression and sedation. Continue monitoring after ketoconazole is stopped, since effects persist.
What other medicines interact with Fentanyl?
MediHelp also lists interactions of Fentanyl with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Fentanyl page.
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