Drug interactions
Diphenhydramine + Methadone
Severity: Moderate
Diphenhydramine and Methadone: moderate 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
Diphenhydramine adds to the sedative and respiratory depressant effects of methadone and can impair alertness and coordination. Anticholinergic effects such as constipation and urinary retention may also be increased.
What this interaction means in plain words
Diphenhydramine and Methadone can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Diphenhydramine belongs to Respiratory; Methadone belongs to Musculoskeletal.
Why it happens
Additive CNS depression from opioid agonism and central H1 antihistamine effects.
What to do
Use the lowest effective diphenhydramine dose and avoid it in elderly or respiratory-compromised patients where possible. Monitor sedation and respiratory status.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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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 Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Methadone?
MediHelp rates the interaction as moderate. Diphenhydramine and Methadone can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Diphenhydramine adds to the sedative and respiratory depressant effects of methadone and can impair alertness and coordination. Anticholinergic effects such as constipation and urinary retention may also be increased.
How serious is the interaction between Diphenhydramine and Methadone?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Use the lowest effective diphenhydramine dose and avoid it in elderly or respiratory-compromised patients where possible. Monitor sedation and respiratory status.
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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