Drug interactions
Doxepin + Methadone
Severity: Major
Doxepin and Methadone: 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 QTc interval, raising the risk of torsades de pointes, and both cause sedation. Doxepin may also modestly raise methadone exposure through CYP2D6 competition.
What this interaction means in plain words
Doxepin 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.
Doxepin belongs to Dermatology; Methadone belongs to Musculoskeletal.
Why it happens
Additive QTc prolongation through cardiac potassium channel blockade plus additive central nervous system depression.
What to do
Obtain a baseline ECG and repeat after dose changes, and correct potassium and magnesium. Use the lowest effective doses and consider an alternative antidepressant if QTc lengthens substantially.
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 Doxepin
- Doxepin + Isocarboxazid Contraindicated
- Doxepin + Phenelzine Contraindicated
- Doxepin + Procarbazine Contraindicated
- Doxepin + Safinamide Contraindicated
- Doxepin + Selegiline Contraindicated
- Doxepin + Tranylcypromine Contraindicated
Frequently asked questions
Can I take Doxepin with Methadone?
MediHelp rates the interaction as major. Doxepin 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 QTc interval, raising the risk of torsades de pointes, and both cause sedation. Doxepin may also modestly raise methadone exposure through CYP2D6 competition.
How serious is the interaction between Doxepin 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 repeat after dose changes, and correct potassium and magnesium. Use the lowest effective doses and consider an alternative antidepressant if QTc lengthens substantially.
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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