Darunavir 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
Darunavir
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.
You're taking amitriptyline (an antidepressant) along with darunavir (an HIV medicine). Darunavir can slow down the liver enzyme that normally breaks down amitriptyline. When that happens, more amitriptyline can build up in your body, which can make its effects stronger.
That could mean more side effects like nausea, dizziness, feeling lightheaded, or even fainting, especially when standing up. The good news is this is very manageable. Your care team can start you on a low dose and adjust it to just what you need, while keeping an eye on how you feel. Please don't change anything on your own, just talk with your pharmacist or doctor.
Effect: Darunavir may inhibit CYP2D6, reducing amitriptyline clearance and increasing TCA exposure. Amitriptyline is an active drug (not a prodrug), so higher exposure means enhanced/prolonged effect and greater risk of anticholinergic, sedative, and cardiac adverse effects.
- Direction: increased amitriptyline exposure (AUC/Cmax)
- Evidence: theoretical; magnitude not quantified
- Onset: unspecified
- Management: use lowest feasible initial/maintenance dose, titrate carefully to response; monitor for nausea, dizziness, orthostatic hypotension, syncope; consider ECG monitoring given TCA cardiotoxicity risk. TCA plasma levels may aid dose individualization.
What happens
Increased tricyclic antidepressant/CYP2D6 substrate exposure
Interaction Deep Dive
When darunavir is given together with agents that function both as TCAs (tricyclic antidepressants) and as substrates of CYP2D6, exposure to these agents may rise, potentially heightening or extending their therapeutic action and possibly leading to adverse events. It is advised to titrate the antidepressant dose cautiously toward the intended effect, which includes selecting the lowest practical starting or maintenance dose, along with observing the antidepressant response12. During combined use, watch for adverse effects including nausea, dizziness, hypotension, and syncope3.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated substrate metabolism by darunavir
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. This interaction is well managed by your care team.
- Your amitriptyline dose may be started low and adjusted and individualized to the smallest amount that works for you.
- Your team may monitor you more closely for both antidepressant response and side effects.
- Watch for and report nausea, dizziness, lightheadedness, or fainting, especially when standing up.
- Bring any new symptoms to your pharmacist or doctor rather than adjusting doses yourself.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Darunavir and Amitriptyline together?
Darunavir can raise amitriptyline levels, so your care team will likely start low, adjust the dose to fit you, and watch for side effects like dizziness or fainting. Keep taking both as prescribed and report new symptoms. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Darunavir 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 Darunavir and Amitriptyline interaction managed?
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. This interaction is well managed by your care team. Your amitriptyline dose may be started low and adjusted and individualized to the smallest amount that works for you. Your team may monitor you more closely for both antidepressant response and side effects. Watch for and report nausea, dizziness, lighthe… 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 Darunavir 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: PREZCOBIX® PED oral tablets for suspension, darunavir cobicistat oral tablets for suspension. Janssen Products, LP (per FDA), Horsham, PA, 2026. DailyMed
- Product Information: PREZCOBIX® oral tablets, darunavir cobicistat oral tablets. Janssen Products, LP (per FDA), Horsham, PA, 2026. DailyMed
- Product Information: PREZISTA(R) oral suspension, oral tablets, darunavir oral suspension, oral tablets. Janssen Products, LP (per FDA), Horsham, PA, 2023. DailyMed
Keep reading about Amitriptyline
Keep reading about Darunavir
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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