Hydroxyzine 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
Hydroxyzine
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.
Both amitriptyline and hydroxyzine can, on their own, slightly affect your heart's electrical rhythm. This shows up on an EKG as something called QT prolongation. When you take both together, these effects can add up, which in rare cases could lead to an abnormal heartbeat.
I want to be clear that this concern is mostly theoretical, meaning it is based on how these drugs work rather than lots of real-world reports. Many people take medicines like these safely. The best thing you can do is let your pharmacist or doctor know you take both so they can keep an eye on things and make sure it is right for you.
Effect: Additive QT interval prolongation with concomitant amitriptyline and hydroxyzine, with a theoretical increased risk of torsades de pointes.
Mechanism: Both agents independently prolong the QT interval; neither is a prodrug relevant here, so the effect is straightforward pharmacodynamic (additive) rather than a metabolic interaction.
- Direction: Additive QT effect (increased risk).
- Severity/Evidence: Major severity, but evidence is theoretical; onset unspecified.
- Management: Assess baseline QTc and cumulative risk factors (electrolyte abnormalities, bradycardia, other QT-prolonging drugs, hepatic impairment). Consider ECG monitoring, correct hypokalemia/hypomagnesemia, and evaluate whether an alternative agent is appropriate.
What happens
An increased risk of QT interval prolongation
Interaction Deep Dive
The use of hydrOXYzine has been linked to prolongation of the QT interval and the emergence of torsade de pointes. Because combining hydrOXYzine with this drug may produce additive QT-prolonging effects, caution should be exercised when the two are administered together1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
The main concern here is that both drugs can nudge your heart rhythm in the same direction, so your care team simply wants to keep the combined effect safe.
- Keep taking both as prescribed unless your doctor tells you otherwise.
- Your team may check an EKG and your potassium and magnesium levels, especially if you have heart concerns.
- Your doses may be adjusted and individualized, or an alternative may be considered, by your care team.
Tell your pharmacist or doctor about all your medicines, and report symptoms like fainting, dizziness, or a fluttering or racing heartbeat right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Hydroxyzine and Amitriptyline together?
Taking amitriptyline and hydroxyzine together can add up to a higher risk of an abnormal heart rhythm (QT prolongation), so keep both providers informed and watch for fainting or palpitations. This risk is largely theoretical and can be managed with monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Hydroxyzine 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 Hydroxyzine and Amitriptyline interaction managed?
The main concern here is that both drugs can nudge your heart rhythm in the same direction, so your care team simply wants to keep the combined effect safe. Keep taking both as prescribed unless your doctor tells you otherwise. Your team may check an EKG and your potassium and magnesium levels, especially if you have heart concerns. Your doses may be adjusted and individualized, or an alternative… 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 Hydroxyzine 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: hydroxyzine HCl oral tablets, hydroxyzine HCl oral tablets. Harris Pharmaceutical, Inc. (per DailyMed), Fort Myers, FL, 2016. DailyMed
Keep reading about Amitriptyline
Keep reading about Hydroxyzine
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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