Drug interactions
Imipramine + Methadone
Severity: Major
Imipramine 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
Both agents can prolong the QT interval, raising the risk of ventricular arrhythmias including torsades de pointes. Sedation is also additive, and imipramine levels may rise because methadone inhibits CYP2D6.
What this interaction means in plain words
Imipramine 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.
Imipramine belongs to Central Nervous System; Methadone belongs to Musculoskeletal.
Why it happens
Additive QTc prolongation and CNS depression, with methadone inhibition of CYP2D6-mediated tricyclic metabolism.
What to do
Check a baseline ECG and repeat after dose changes, and keep electrolytes normal. Consider tricyclic plasma levels or a lower imipramine dose, or choose a less QT-active 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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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 Imipramine
- Dronedarone + Imipramine Contraindicated
- Imipramine + Isocarboxazid Contraindicated
- Imipramine + Phenelzine Contraindicated
- Imipramine + Pimozide Contraindicated
- Imipramine + Rasagiline Contraindicated
- Imipramine + Safinamide Contraindicated
Frequently asked questions
Can I take Imipramine with Methadone?
MediHelp rates the interaction as major. Imipramine 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. Both agents can prolong the QT interval, raising the risk of ventricular arrhythmias including torsades de pointes. Sedation is also additive, and imipramine levels may rise because methadone inhibits CYP2D6.
How serious is the interaction between Imipramine 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: Check a baseline ECG and repeat after dose changes, and keep electrolytes normal. Consider tricyclic plasma levels or a lower imipramine dose, or choose a less QT-active 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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