Amitriptyline and Amantadine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amantadine
No brand names on recordAmitriptyline
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Both of these medicines have drying, 'anticholinergic' effects, and taking them together can add up. Amantadine has mild atropine-like activity, and amitriptyline (Elavil) is well known for causing dry mouth, blurry vision, constipation, trouble urinating, and drowsiness. When you take them together, those effects can become stronger.
In some people, especially at higher doses, this can even lead to confusion or seeing things that aren't there (hallucinations). This is based mostly on theory, so it doesn't happen to everyone. The good news is your care team can manage this by adjusting your doses and keeping an eye on you. Let them know if you notice new dryness, confusion, or trouble going to the bathroom.
Interaction: Additive anticholinergic burden. Both amantadine (atropine-like properties) and amitriptyline (a tertiary amine TCA with strong antimuscarinic activity) act pharmacodynamically at muscarinic receptors; neither is a prodrug here.
- Direction: Potentiation of anticholinergic effects (increased effect).
- Manifestations: Dry mouth, blurred vision, urinary retention, constipation, tachycardia, and CNS effects including confusion and hallucinations, particularly near maximally tolerated anticholinergic doses.
- Evidence: Theoretical/PD-based; severity rated major.
- Onset: Unspecified.
- Management: Monitor for atropine-like toxicity, especially in elderly or high-dose patients. If effects occur, dose of either agent may be reduced and individualized.
What happens
Potentiation of anticholinergic effects
Interaction Deep Dive
Taking amantadine together with anticholinergic agents can heighten amantadine's anticholinergic-type adverse effects21. In patients treated with doses approaching the maximum tolerable amount of an anticholinergic (trihexyphenidyl, benztropine), joint administration has led to intensified anticholinergic side effects, such as hallucinations and confusion3. When simultaneous use cannot be avoided, decrease the dose of either amantadine or the anticholinergic agent should atropine-like side effects develop2.
Why it happens (mechanism)
Additive anticholinergic properties
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination can be used with appropriate monitoring.
- Your care team may watch you more closely for atropine-like side effects (dry mouth, blurred vision, constipation, difficulty urinating, confusion, or hallucinations).
- If these side effects appear, the dose of amitriptyline or amantadine may be adjusted and individualized by your team.
- Older adults and those on higher doses need extra attention.
What to do: Tell your pharmacist or doctor promptly if you notice new dryness, trouble urinating, confusion, or visual changes, so they can tailor your treatment.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The combined use of amantadine with anticholinergic medications has been documented to enhance anticholinergic adverse effects, such as confusion and hallucinations, in patients taking near-maximal tolerated doses of an anticholinergic (trihexyphenidyl, benztropine) 3.
Common questions
Can I take Amitriptyline and Amantadine together?
Combining amantadine and amitriptyline can stack up anticholinergic side effects like dry mouth, constipation, urinary trouble, and even confusion. Watch for these symptoms and report them, since your care team can adjust the doses if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Amantadine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Amitriptyline and Amantadine interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination can be used with appropriate monitoring. Your care team may watch you more closely for atropine-like side effects (dry mouth, blurred vision, constipation, difficulty urinating, confusion, or hallucinations). If these side effects appear, the dose of amitriptyline or amantadine may be adjusted and… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Amitriptyline or Amantadine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- Product Information: PREVDUO intravenous injection, neostigmine methylsulfate glycopyrrolate intravenous injection. Slayback Pharma LLC (per FDA), Princeton, NJ, 2023. DailyMed
- Product Information: OSMOLEX ER(TM) oral extended-release tablets, amantadine oral extended-release tablets. Vertical Pharmaceuticals, LLC (per manufacturer), Bridgewater, NJ, 2018. DailyMed
- Postma JU & Tilburg WV: Visual hallucinations and delirium during treatment with amantadine (Symmetrel(R)). J Am Geriatr Soc 1975; 23:212-215. PubMed
Keep reading about Amantadine
Keep reading about Amitriptyline
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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