Efavirenz 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
Efavirenz
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 of these medicines can affect your heart's rhythm. Amitriptyline (Elavil) and efavirenz can each slightly change the timing of your heartbeat, something doctors call the QT interval. When you take them together, those small effects can add up and, in rare cases, lead to an irregular heartbeat.
The good news is that this concern is mostly based on how the drugs work rather than on lots of real-world problems. Please don't stop either medication on your own. Talk with your pharmacist or doctor. They can decide whether a different option makes sense, or keep a closer eye on your heart to keep you safe.
Effect: Additive QT-interval prolongation with increased risk of torsade de pointes when amitriptyline and efavirenz are combined.
- Mechanism: Pharmacodynamic additive effect; both agents independently prolong the QTc. Neither is a prodrug here, so the direction is additive PD toxicity, not altered activation.
- Magnitude/onset: Efavirenz caused mean QTc prolongation ~8.7 ms in CYP2B6 *6/*6 subjects (Cmax 2.25-fold higher vs *1/*1). Onset unspecified.
- Evidence: Theoretical/additive.
- Management: Consider an alternative to efavirenz. If co-administered, obtain baseline and follow-up ECGs, correct K+/Mg2+, and review other QT-prolonging agents.
What happens
An increased risk of QT interval prolongation
Interaction Deep Dive
When efavirenz is given together with a medication that lengthens the QT interval or carries a recognized risk of torsade de pointes, alternative agents should be considered, since the effects on the QT interval can be additive. Data from a QT study involving 58 healthy volunteers showed that individuals carrying the CYP2B6 *6/*6 genotype had a mean Cmax that was 2.25-fold greater than the mean Cmax observed in those with the CYP2B6 *1/*1 genotype, while the mean prolongation of the QTc interval reached 8.7 milliseconds among subjects with the CYP2B6 *6/*6 genotype1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
This is manageable with the right plan from your care team. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may consider an alternative to efavirenz, since that is the main approach on file for combining it with a QT-prolonging drug like amitriptyline.
- If you stay on both, they may monitor you more closely, which can include heart rhythm checks.
- Ask your pharmacist to review your full list, since other medicines can also affect heart rhythm.
- Report fainting, dizziness, or a fluttering or pounding heartbeat right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a QT investigation involving healthy volunteers (N=58) selected to include CYP2B6 polymorphisms, a positive relationship between efavirenz levels and QTc prolongation was noted. After efavirenz 600 mg/day was given for 14 days, the mean Cmax among subjects carrying the CYP2B6 *6/*6 genotype was 2.25-fold greater than the mean Cmax among subjects with the CYP2B6 *1/*1 genotype, and the mean QTc interval prolongation reached 8.7 milliseconds in subjects with the CYP2B6 *6/*6 genotype 1.
Common questions
Can I take Efavirenz and Amitriptyline together?
Taking amitriptyline with efavirenz can add up to raise the risk of a QT-related heart rhythm problem, so ask your care team whether an alternative or closer monitoring is right for you. Do not stop either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Efavirenz 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 Efavirenz and Amitriptyline interaction managed?
This is manageable with the right plan from your care team. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your care team may consider an alternative to efavirenz, since that is the main approach on file for combining it with a QT-prolonging drug like amitriptyline. If you stay on both, they may monitor you more closely, which can include heart rhythm… 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 Efavirenz 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: SUSTIVA(R) oral capsules, oral tablets, efavirenz oral capsules, oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023. DailyMed
Keep reading about Amitriptyline
Keep reading about Efavirenz
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major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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