Drug interactions
Ketoconazole + Methadone
Severity: Major
Ketoconazole and Methadone: 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 inhibits CYP3A4 and raises methadone exposure, risking excess sedation and respiratory depression. Both drugs also prolong the QT interval, so torsades de pointes is a concern.
What this interaction means in plain words
Ketoconazole and Methadone 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 belongs to Anti Fungals; Methadone belongs to Musculoskeletal.
Why it happens
CYP3A4 inhibition reduces methadone metabolism, combined with additive QT prolongation.
What to do
Avoid if possible; if unavoidable, reduce the methadone dose and monitor ECG, QTc, electrolytes and sedation. Reassess dose when ketoconazole is stopped.
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?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Ketoconazole and Methadone, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 14 days on the web. No card needed.
Other interactions of Methadone
- Alvimopan + Methadone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Methadone Contraindicated
- Droperidol + Methadone Contraindicated
- Ibutilide + Methadone Contraindicated
- Isocarboxazid + Methadone Contraindicated
- Lefamulin + Methadone Contraindicated
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 Ketoconazole with Methadone?
MediHelp rates the interaction as major. Ketoconazole and Methadone 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 inhibits CYP3A4 and raises methadone exposure, risking excess sedation and respiratory depression. Both drugs also prolong the QT interval, so torsades de pointes is a concern.
How serious is the interaction between Ketoconazole and Methadone?
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 if possible; if unavoidable, reduce the methadone dose and monitor ECG, QTc, electrolytes and sedation. Reassess dose when ketoconazole is stopped.
What other medicines interact with Methadone?
MediHelp also lists interactions of Methadone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Droperidol. The full list is on the Methadone page.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
