Drug interactions
Amitriptyline + Difenoxin
Severity: Moderate
Amitriptyline and Difenoxin: 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
Difenoxin is an opioid antidiarrheal metabolite of diphenoxylate with CNS depressant potential. Combined with amitriptyline, additive sedation may occur and both drugs reduce gut motility, raising the risk of constipation or ileus.
What this interaction means in plain words
Amitriptyline and Difenoxin 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.
Amitriptyline belongs to Central Nervous System; Difenoxin belongs to Gastrointestinal Tract.
Why it happens
Additive CNS depression from opioid activity and amitriptyline sedation, plus additive anticholinergic effects on gut motility.
What to do
Monitor for sedation and signs of reduced bowel motility such as abdominal distension. Use the lowest effective doses and avoid alcohol.
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 Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide Contraindicated
Other interactions of Difenoxin
Frequently asked questions
Can I take Amitriptyline with Difenoxin?
MediHelp rates the interaction as moderate. Amitriptyline and Difenoxin 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. Difenoxin is an opioid antidiarrheal metabolite of diphenoxylate with CNS depressant potential. Combined with amitriptyline, additive sedation may occur and both drugs reduce gut motility, raising the risk of constipation or ileus.
How serious is the interaction between Amitriptyline and Difenoxin?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for sedation and signs of reduced bowel motility such as abdominal distension. Use the lowest effective doses and avoid alcohol.
What other medicines interact with Amitriptyline?
MediHelp also lists interactions of Amitriptyline with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Amitriptyline page.
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