Iloperidone and Amitriptyline: 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
Iloperidone
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 can affect your heart's rhythm. Amitriptyline (Elavil) is an older antidepressant, and iloperidone (Fanapt) treats certain mental health conditions. Each one can slightly stretch out the time your heart takes to reset between beats. This is called QT prolongation. When you take them together, that effect can add up and, in rare cases, lead to a dangerous heart rhythm.
Please don't stop either medicine on your own. This is something your doctor and pharmacist can manage carefully. Let them know if you feel a racing heart, dizziness, fainting, or lightheadedness, and keep them in the loop about all your medications.
Interaction: Additive QT-interval prolongation when amitriptyline is combined with iloperidone. Both agents independently prolong the QTc, so concurrent use increases the risk of torsades de pointes and other ventricular arrhythmias. This is a pharmacodynamic (additive), not pharmacokinetic, interaction; neither drug's metabolism drives it.
- Direction: Additive QT effect (increased arrhythmia risk)
- Severity: Major; evidence: probable
- Management: Manufacturer labeling advises avoiding iloperidone with other QT-prolonging drugs. If co-use is unavoidable, obtain baseline and follow-up ECGs, correct electrolytes (K+, Mg2+), review other QT-prolonging agents, and monitor for symptoms. Dosing should be individualized by the care team.
What happens
An increased risk of QT interval prolongation
Interaction Deep Dive
Do not administer iloperidone alongside any medication known to lengthen the QT interval. Taking iloperidone together with a QT prolonging agent can produce additive prolongation of the QT interval, thereby raising the likelihood of cardiac arrhythmia1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Because both can affect heart rhythm, your team will decide how best to handle this combination.
- Your doctor may check an ECG (heart tracing) before and during treatment.
- They may check your potassium and magnesium levels, since low levels raise the risk.
- They may consider an alternative medicine or adjust and individualize your doses.
Contact your prescriber or pharmacist right away if you feel a fast or irregular heartbeat, dizziness, fainting, or lightheadedness. Share a full list of all your medications so they can spot other heart-rhythm risks.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In an open-label QTc study involving patients diagnosed with schizophrenia or schizoaffective disorder (n=160), iloperidone administered at 12 mg twice daily was linked to a QTc prolongation of 9 milliseconds 1.
Common questions
Can I take Iloperidone and Amitriptyline together?
Amitriptyline and iloperidone can each prolong the QT interval, and together the risk of a dangerous heart rhythm adds up. Don't stop either on your own; your care team may run ECGs, check electrolytes, or adjust therapy. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Iloperidone and Amitriptyline 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 Iloperidone and Amitriptyline interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Because both can affect heart rhythm, your team will decide how best to handle this combination. Your doctor may check an ECG (heart tracing) before and during treatment. They may check your potassium and magnesium levels, since low levels raise the risk. They may consider an alternative medicine or adjust… 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 Iloperidone or Amitriptyline 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 (1)
- Product Information: FANAPT(R) oral tablets, iloperidone oral tablets. Vanda Pharmaceuticals Inc (per FDA), Washington, DC, 2024. DailyMed
Keep reading about Amitriptyline
Keep reading about Iloperidone
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