Posaconazole 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
Posaconazole
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.
Amitriptyline (Elavil) and posaconazole (Noxafil) can each affect the heart's electrical rhythm in a way doctors call QT prolongation. When you take both together, that effect can add up, which may raise the chance of an irregular heartbeat.
This concern is based on how these drugs work rather than lots of reported cases, but because heart rhythm is serious, the guidance is to avoid using them together. The good news: your care team can manage this easily, usually by choosing a different medicine for one of them. Please don't stop either drug on your own. Just talk with your pharmacist or doctor so they can pick the safest option for you.
Interaction: Additive QT interval prolongation with concomitant amitriptyline and posaconazole.
- Mechanism: Pharmacodynamic. Both agents independently prolong the QT interval; the effect is additive. Neither is a prodrug here, so direction is a combined PD effect, not a PK activation issue.
- Direction/magnitude: Increased risk of QTc prolongation and torsades de pointes; magnitude not quantified.
- Onset: Unspecified.
- Evidence: Theoretical.
- Management: Avoid coadministration per labeling. If unavoidable, consider ECG and electrolyte (K+, Mg2+) monitoring and review other QT-prolonging agents. Severity rated major.
What happens
An increased risk of QT interval prolongation
Interaction Deep Dive
Posaconazole should not be given together with this drug12. When the two are used at the same time, the effect on the QT interval may be additive, leading to further prolongation3.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
What your care team may do:
- Because the recommendation is to avoid using these two together, they will most likely select an alternative medicine for either the depression/pain indication or the antifungal.
- If both are truly needed, they may monitor you more closely, including checking your heart rhythm (ECG) and correcting electrolytes such as potassium and magnesium.
What you should do: Keep taking both exactly as prescribed until you speak with your pharmacist or doctor. Let them know if you feel palpitations, dizziness, or fainting. Ask whether a safer substitute is right for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Posaconazole and Amitriptyline together?
Amitriptyline and posaconazole can each stretch out the heart's QT interval, and together the effect adds up, so guidance is to avoid combining them; ask your pharmacist or doctor about an alternative rather than stopping anything yourself. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Posaconazole 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 Posaconazole and Amitriptyline interaction managed?
What your care team may do: Because the recommendation is to avoid using these two together, they will most likely select an alternative medicine for either the depression/pain indication or the antifungal. If both are truly needed, they may monitor you more closely, including checking your heart rhythm (ECG) and correcting electrolytes such as potassium and magnesium. What you should do: Keep tak… 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 Posaconazole 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 (3)
- Product Information: NOXAFIL® PowderMix delayed-release oral suspension, posaconazole delayed-release oral suspension. Merck Sharp & Dohme LLC (per FDA), Rahway, NJ, 2026. DailyMed
- Product Information: NOXAFIL® intravenous injection, oral delayed-release tablets, oral suspension, posaconazole intravenous injection, oral delayed-release tablets, oral suspension. Merck Sharp & Dohme LLC (per FDA), Rahway, NJ, 2026. DailyMed
- Product Information: Posaconazole oral delayed-release tablets, posaconazole oral delayed-release tablets. SpecGx LLC (per DailyMed), Webster Groves, MO, 2024. DailyMed
Keep reading about Amitriptyline
Keep reading about Posaconazole
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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