Drug interactions
Methadone + Promethazine
Severity: Major
Methadone and Promethazine: major interaction.
Last updated Sources: US FDA label
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
Both drugs can prolong the QT interval, so the combination raises the risk of torsades de pointes, especially at higher methadone doses or with electrolyte disturbances. Promethazine also adds sedation and respiratory depression to methadone's opioid effects.
What this interaction means in plain words
Methadone and Promethazine 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.
Methadone belongs to Musculoskeletal; Promethazine belongs to Respiratory.
Why it happens
Additive QT prolongation through cardiac potassium channel blockade, plus additive CNS and respiratory depression.
What to do
Obtain a baseline and follow-up ECG, correct hypokalemia and hypomagnesemia, and monitor for sedation and respiratory depression. Prefer a non-QT-prolonging antiemetic or antihistamine when possible.
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 Methadone and Promethazine, 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 7 days on the web. No card needed.
References
Other interactions of Promethazine
- Ibutilide + Promethazine Contraindicated
- Pimozide + Promethazine Contraindicated
- Promethazine + Thioridazine Contraindicated
- Alfentanil + Promethazine Major
- Amiodarone + Promethazine Major
- Amisulpride + Promethazine Major
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
Frequently asked questions
Can I take Methadone with Promethazine?
MediHelp rates the interaction as major. Methadone and Promethazine 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. Both drugs can prolong the QT interval, so the combination raises the risk of torsades de pointes, especially at higher methadone doses or with electrolyte disturbances. Promethazine also adds sedation and respiratory depression to methadone's opioid effects.
How serious is the interaction between Methadone and Promethazine?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Obtain a baseline and follow-up ECG, correct hypokalemia and hypomagnesemia, and monitor for sedation and respiratory depression. Prefer a non-QT-prolonging antiemetic or antihistamine when possible.
What other medicines interact with Promethazine?
MediHelp also lists interactions of Promethazine with, for example, Ibutilide, Pimozide, Thioridazine. The full list is on the Promethazine 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.
