Amitriptyline and Cimetidine: 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
Amitriptyline
Cimetidine
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.
Here's what's going on. Cimetidine (Tagamet) slows down how your body breaks down amitriptyline (Elavil). That means more amitriptyline can build up in your blood, and its side effects can get stronger. You might notice things like dry mouth, blurry vision, trouble urinating, drowsiness, or constipation.
The good news is this is very manageable. Your care team may use a lower amitriptyline dose and can check a blood level in the first few days after you start or stop cimetidine. Please don't change anything on your own, just talk with your pharmacist or doctor so they can tailor things for you.
Mechanism: Cimetidine inhibits hepatic metabolism of amitriptyline (a substrate, not a prodrug), decreasing clearance and increasing serum amitriptyline exposure. Effect is increased tricyclic activity and anticholinergic toxicity.
- Direction: increased amitriptyline levels/effect
- Onset: delayed
- Evidence: probable
- Severity: moderate
Management: If coadministered, lower-than-usual amitriptyline doses may be required. Consider checking serum amitriptyline levels within the first few days of starting or stopping cimetidine. Monitor for anticholinergic effects (dry mouth, blurred vision, urinary retention) and sedation. An alternative H2 blocker such as ranitidine or famotidine, which do not appear to impair amitriptyline metabolism, may be preferred.
What happens
Amitriptyline toxicity (dry mouth, blurred vision, urinary retention)
Interaction Deep Dive
By slowing the breakdown of amitriptyline, cimetidine raises its serum concentration234. When the two drugs must be given together, amitriptyline doses lower than those typically used may be needed. During the initial few days after cimetidine is either started or stopped, monitoring serum amitriptyline levels may be worth considering1.
Why it happens (mechanism)
Decreased amitriptyline metabolism
How to manage this interaction
This can be managed safely. Keep taking both medicines exactly as prescribed unless your care team tells you otherwise.
- Your prescriber may use a lower-than-usual amitriptyline dose while you are on cimetidine.
- They may check an amitriptyline blood level in the first few days after you start or stop cimetidine, and adjust as needed.
- A different acid reducer such as ranitidine or famotidine may be an option, since these don't seem to affect amitriptyline the same way.
What to do: Tell your pharmacist or doctor you take both, and report any dry mouth, blurred vision, trouble urinating, or extra drowsiness.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amitriptyline and Cimetidine together?
Cimetidine can raise amitriptyline levels and increase side effects like dry mouth, blurred vision, and urinary retention. Don't change anything yourself, but ask your pharmacist or doctor whether a lower amitriptyline dose, a blood level check, or a different acid reducer (like famotidine) makes sense. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Cimetidine interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Amitriptyline and Cimetidine interaction managed?
This can be managed safely. Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Your prescriber may use a lower-than-usual amitriptyline dose while you are on cimetidine. They may check an amitriptyline blood level in the first few days after you start or stop cimetidine, and adjust as needed. A different acid reducer such as ranitidine or famotidine may be… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
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 Cimetidine 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 anything you'd monitor while I'm on both?
References (4)
- Product Information: amitriptyline HCl oral tablet, amitriptyline HCl oral tablet. RemedyRepack Inc. (per DailyMed), Indiana, PA, 2010. DailyMed
- Curry SH, DeVane CL, & Wolfe MM: Cimetidine interaction with amitriptyline. Eur J Clin Pharmacol 1985; 29:429-433. DOI
- Curry SH, DeVane CL, & Wolfe MM: Lack of interaction of ranitidine with amitriptyline. Eur J Clin Pharmacol 1987; 32:317-320. PubMed
- Wells BG, Pieper JA, Self TH, et al: The effect of ranitidine and cimetidine on imipramine disposition. Eur J Clin Pharmacol 1986; 31:285-290. PubMed
Keep reading about Amitriptyline
Keep reading about Cimetidine
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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