Drug interactions
Methadone + Trimipramine
Severity: Major
Methadone and Trimipramine: 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 agents can prolong the QT interval, and tricyclic antidepressants add to sedation and anticholinergic effects. Trimipramine is also metabolised by CYP2D6, and methadone may raise tricyclic concentrations. Together these increase the risk of arrhythmia and CNS depression.
What this interaction means in plain words
Methadone and Trimipramine 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; Trimipramine belongs to Central Nervous System.
Why it happens
Additive QT prolongation and CNS depression, with possible inhibition of CYP2D6 by methadone raising tricyclic levels.
What to do
Obtain a baseline ECG and repeat it after dose changes, and correct electrolyte abnormalities. Consider an antidepressant with less cardiac effect, or use lower trimipramine doses with monitoring for sedation.
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
Other interactions of Trimipramine
- Disopyramide + Trimipramine Contraindicated
- Dofetilide + Trimipramine Contraindicated
- Ibutilide + Trimipramine Contraindicated
- Isocarboxazid + Trimipramine Contraindicated
- Pentamidine + Trimipramine Contraindicated
- Phenelzine + Trimipramine Contraindicated
Frequently asked questions
Can I take Methadone with Trimipramine?
MediHelp rates the interaction as major. Methadone and Trimipramine 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 agents can prolong the QT interval, and tricyclic antidepressants add to sedation and anticholinergic effects. Trimipramine is also metabolised by CYP2D6, and methadone may raise tricyclic concentrations. Together these increase the risk of arrhythmia and CNS depression.
How serious is the interaction between Methadone and Trimipramine?
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 it after dose changes, and correct electrolyte abnormalities. Consider an antidepressant with less cardiac effect, or use lower trimipramine doses with monitoring for sedation.
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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