Amitriptyline and Ketoconazole: 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
Ketoconazole
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 (a medicine often used for depression, nerve pain, or sleep) and oral ketoconazole (an antifungal taken by mouth) can each affect the heart's rhythm in a small way. They can slightly stretch out a part of the heartbeat called the QT interval. When you take both together, that effect can add up and, in rare cases, lead to an irregular heartbeat.
The good news is that this is a theoretical concern, meaning it is based on how the drugs work rather than lots of real-world cases. Your care team can manage this easily by watching you a bit more closely. Please don't stop either medicine on your own, just check in with your pharmacist or doctor.
Effect: Additive QT interval prolongation when amitriptyline is combined with oral ketoconazole.
Mechanism: Both agents independently prolong the QT interval; the effect is pharmacodynamically additive. (Note: ketoconazole is also a strong CYP3A4 inhibitor and can raise amitriptyline exposure, but the documented concern here is the additive PD QT effect.)
- Direction: increased combined QT risk
- Onset: unspecified
- Evidence: theoretical
- Severity: major
Management: Assess baseline QTc and electrolytes (K+, Mg2+), review other QT-prolonging agents, and monitor ECG as clinically indicated. Individualize therapy; consider alternatives if additional risk factors are present.
What happens
An increased risk for QT interval prolongation
Interaction Deep Dive
When amitriptyline is given concurrently with oral ketoconazole, the likelihood of QT interval prolongation may be elevated21.
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 nudge your heart rhythm, your team may take steps to keep you safe.
- They may check an ECG (heart tracing) and your blood levels of potassium and magnesium.
- They may review your other medicines to see if anything else affects heart rhythm.
- Your doses may be adjusted and individualized, or an alternative may be chosen if needed.
Tell your doctor or pharmacist if you feel a fast, pounding, or irregular heartbeat, dizziness, or fainting. These are worth reporting right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amitriptyline and Ketoconazole together?
Taking amitriptyline with oral ketoconazole may add up to affect your heart rhythm (QT interval), so keep both as prescribed but ask your care team about heart monitoring and report any palpitations, dizziness, or fainting. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Ketoconazole 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 Ketoconazole interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Because both can nudge your heart rhythm, your team may take steps to keep you safe. They may check an ECG (heart tracing) and your blood levels of potassium and magnesium. They may review your other medicines to see if anything else affects heart rhythm. Your doses may be adjusted and individualized, or an… 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 Ketoconazole 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 (2)
- Product Information: amitriptyline HCl oral film coated tablets, amitriptyline HCl oral film coated tablets. Sandoz Inc. (per DailyMed), Princeton, NJ, 2010. DailyMed
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
Keep reading about Amitriptyline
Keep reading about Ketoconazole
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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