Everolimus and Cobicistat: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cobicistat
Everolimus
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.
What happens
Increased everolimus exposure and an increased cobicistat exposure
Interaction Deep Dive
Avoid coadministration of everolimus with cobicistat (dual strong CYP3A4 and P-gp inhibitor) due to the potential for elevated everolimus exposure21. If concurrent therapy is necessary in transplant recipients, closely monitor everolimus whole blood trough levels 3. Coadministration of cobicistat with atazanavir or darunavir in combination with other drugs that inhibit CYP3A4, such as everolimus may further increase exposure of cobicistat, atazanavir, and darunavir 4.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of everolimus; inhibition of P-gp mediated efflux transport of everolimus; inhibition of CYP3A4-mediated metabolism of cobicistat
Literature reports
2 reports — tap to read
a) A 78-year-old female heart transplant recipient receiving everolimus-based immunosuppressive therapy for 11 years (1 mg every 12 hours) with stable trough levels experienced an 11.4-fold increase in everolimus (greater than 20 nanograms (ng)/mL) 4 days following initiation of clarithromycin (500 mg ever 12 hours) for the treatment of pneumonia. Despite a reduction in everolimus to 0.25 mg every 12 hours, her everolimus level remained elevated (18.59 ng/mL). Upon discontinuation of clarithromycin, the everolimus Cmin returned to a stable level of 8.53 ng/mL. The patient did not experience any adverse events 5.
b) Coadministration of everolimus (a CYP3A4 and P-gp substrate) and ketoconazole (a strong CYP3A4 and P-gp inhibitor) in healthy volunteers increased everolimus Cmax by 3.9-fold, AUC by 15-fold, and half-life by 89% 3.
Common questions
Can I take Everolimus and Cobicistat together?
Increased everolimus exposure and an increased cobicistat exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Everolimus and Cobicistat 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 strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Everolimus or Cobicistat 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 (5)
- Product Information: AFINITOR DISPERZ® tablets for oral suspension, everolimus tablets for oral suspension. Novartis Pharmaceuticals Corporation, East Hanover, NJ, 2026. DailyMed
- Product Information: AFINITOR® oral tablets, everolimus oral tablets. Novartis Pharmaceuticals Corporation, East Hanover, NJ, 2026. DailyMed
- Product Information: ZORTRESS(R) oral tablets, everolimus oral tablets. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
- Product Information: TYBOST(R) oral tablets, cobicistat oral tablets. Gilead Sciences Inc (per FDA), Foster City, CA, 2025. DailyMed
- Pea F, Cojutti P, Tursi V, et al: Everolimus overexposure in a heart transplant patient receiving clarithromycin for the treatment of pneumonia. Transpl Infect Dis 2015; 17(6):926-928. PubMed
Keep reading about Cobicistat
Keep reading about Everolimus
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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