Amitriptyline and Anisindione: 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
Anisindione
No brand names on record
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. Anisindione is a blood thinner. Amitriptyline (Elavil) is an antidepressant that can also help with sleep and nerve pain. When you take them together, the amitriptyline may cause your body to hold onto the blood thinner a bit longer and absorb more of it. That can make the blood thinner stronger than intended, which raises the chance of bleeding.
The good news is this is very manageable. This is a theoretical concern, and people react quite differently to it. Your care team can watch your blood clotting tests (INR) and fine-tune your blood thinner dose so you stay in a safe range. Please don't change either medicine on your own, just talk with your pharmacist or doctor.
Effect: TCAs may increase anisindione exposure via decreased metabolism and increased bioavailability, prolonging its half-life and enhancing anticoagulant effect. Neither agent's activation depends on the other, so the direction is a net increase in anticoagulant activity and bleeding risk.
- Direction: increased anisindione effect (higher INR/bleeding risk)
- Onset: delayed
- Evidence: theoretical; considerable interindividual variability
- Severity: moderate
Management: Closely monitor PT ratio/INR when starting or stopping the TCA, and reassess periodically during concurrent use. Anticoagulant dose may need individualized adjustment. Watch for bleeding/bruising.
What happens
An increased risk of bleeding
Interaction Deep Dive
Oral anticoagulants may have their half-life and bioavailability raised by tricyclic antidepressants (TCAs)23. Substantial variation between individuals can occur1.
Why it happens (mechanism)
Decreased anisindione metabolism; increased anisindione absorption
How to manage this interaction
This combination can be managed safely with monitoring. Keep taking both medications exactly as prescribed unless your care team tells you otherwise.
- Expect more frequent INR (blood clotting) checks, especially when the amitriptyline is started, stopped, or its dose changes.
- Your blood thinner dose may need to be adjusted and individualized by your care team to keep you in a safe range.
- Watch for signs of bleeding: unusual bruising, nosebleeds, pink or red urine, black stools, or gums that bleed easily, and report them promptly.
Bring any concerns to your pharmacist or prescriber so they can tailor your plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) In a trial involving healthy volunteers, taking nortriptyline or amitriptyline at the same time led to higher dicumarol levels and a longer plasma half-life of dicumarol, though this effect was not seen consistently across all participants 1. The same effect did not occur with warfarin.
b) A single oral dose of bishydroxycoumarin given after 8 days of nortriptyline produced a significantly extended half-life and a reduced volume of distribution of the coumarin anticoagulant in 6 healthy volunteers 2. The proposed mechanism was decreased bishydroxycoumarin metabolism and/or changed coumarin absorption.
c) Drug dosing was examined in 16 patients receiving long-term anticoagulant therapy who were also taking TCAs concurrently 3. The TCAs disrupted the stability of anticoagulant control, resulting in frequent adjustments to the anticoagulant doses. The suggested mechanism was inhibition of coumarin metabolism.
Common questions
Can I take Amitriptyline and Anisindione together?
Amitriptyline may boost the blood-thinning effect of anisindione and raise bleeding risk, so your team will monitor your INR closely and adjust the anticoagulant dose as needed. Keep taking both as prescribed and report any unusual bleeding. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Anisindione 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 Anisindione interaction managed?
This combination can be managed safely with monitoring. Keep taking both medications exactly as prescribed unless your care team tells you otherwise. Expect more frequent INR (blood clotting) checks, especially when the amitriptyline is started, stopped, or its dose changes. Your blood thinner dose may need to be adjusted and individualized by your care team to keep you in a safe range. Watch for… 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 Anisindione 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 (3)
- Pond SM, Graham GG, Birkett DJ, et al: Effects of tricyclic antidepressants on drug metabolism. Clin Pharmacol Ther 1975; 18:191-199. PubMed
- Vesell ES, Passananti GT, & Greene FE: Impairment of drug metabolism in man by allopurinol and nortriptyline. N Engl J Med 1970; 283:1484-1488. PubMed
- Williams JR, Griffin JP, & Parkins A: Effect of concomitantly administered drugs on the control of long term anticoagulant therapy. Q J Med 1976; 45:63-73. DOI
Keep reading about Amitriptyline
Keep reading about Anisindione
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist