Drug interactions
Diphenoxylate + Methadone
Severity: Moderate
Diphenoxylate 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
Diphenoxylate is an opioid antidiarrheal that can cause central nervous system depression at higher doses. Together with methadone it can add to sedation and respiratory depression, and worsen constipation.
What this interaction means in plain words
Diphenoxylate 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.
Diphenoxylate belongs to Gastrointestinal Tract; Methadone belongs to Musculoskeletal.
Why it happens
Additive opioid receptor agonism causing central nervous system depression.
What to do
Keep diphenoxylate at the lowest effective dose and monitor for sedation and respiratory depression. Counsel the patient not to take extra doses.
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 Diphenoxylate
Frequently asked questions
Can I take Diphenoxylate with Methadone?
MediHelp rates the interaction as moderate. Diphenoxylate 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. Diphenoxylate is an opioid antidiarrheal that can cause central nervous system depression at higher doses. Together with methadone it can add to sedation and respiratory depression, and worsen constipation.
How serious is the interaction between Diphenoxylate 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: Keep diphenoxylate at the lowest effective dose and monitor for sedation and respiratory depression. Counsel the patient not to take extra doses.
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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