Drug interactions
Amitriptyline + Methadone
Severity: Major
Amitriptyline 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 drugs can prolong the QT interval and raise the risk of torsades de pointes, and both cause sedation. Amitriptyline may also increase methadone levels through CYP inhibition.
What this interaction means in plain words
Amitriptyline 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.
Amitriptyline belongs to Central Nervous System; Methadone belongs to Musculoskeletal.
Why it happens
Additive QT prolongation and CNS depression, with possible CYP2D6/3A4 related pharmacokinetic effects.
What to do
Obtain a baseline ECG and monitor QTc, correct potassium and magnesium, and watch for sedation. Consider an alternative antidepressant if QTc becomes prolonged.
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 Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide Contraindicated
Frequently asked questions
Can I take Amitriptyline with Methadone?
MediHelp rates the interaction as major. Amitriptyline 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 drugs can prolong the QT interval and raise the risk of torsades de pointes, and both cause sedation. Amitriptyline may also increase methadone levels through CYP inhibition.
How serious is the interaction between Amitriptyline 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: Obtain a baseline ECG and monitor QTc, correct potassium and magnesium, and watch for sedation. Consider an alternative antidepressant if QTc becomes prolonged.
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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