Drug interactions
Methadone + Protriptyline
Severity: Major
Methadone and Protriptyline: 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 together they raise the risk of torsades de pointes. Additive sedation and anticholinergic effects may also occur, and methadone can raise tricyclic antidepressant levels.
What this interaction means in plain words
Methadone and Protriptyline 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.
Why it happens
Additive QT prolongation and CNS depression, with possible CYP2D6 inhibition by methadone raising tricyclic levels.
What to do
Obtain a baseline ECG and repeat after changes, correcting potassium and magnesium. Avoid the combination in patients with QT risk factors or consider an alternative antidepressant.
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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References
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 Protriptyline?
MediHelp rates the interaction as major. Methadone and Protriptyline 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 together they raise the risk of torsades de pointes. Additive sedation and anticholinergic effects may also occur, and methadone can raise tricyclic antidepressant levels.
How serious is the interaction between Methadone and Protriptyline?
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 ECG and repeat after changes, correcting potassium and magnesium. Avoid the combination in patients with QT risk factors or consider an alternative antidepressant.
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.
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