Everolimus

mTOR kinase inhibitor – immunosuppressant and antineoplastic

ATC code: L01EG02

Brand names: Afinitor, Certican, Votubia, Zortress

Updated 4 Jun 2026 · Methodology

Indications

ER-positive breast cancer

Second line

Combined with exemestane in metastatic ER+ HER2-negative breast cancer after non-steroidal aromatase inhibitor progression (letrozole, anastrozole) per ESMO 2024. Dose 10 mg daily. BOLERO-2 doubled progression-free survival (4.1 to 10.6 months).

Sources

N Engl J Med: Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. (2012)
AEMPS: Ficha tecnica de Certican (everolimus) (2024)
Ann Oncol: ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. (2021)
AEMPS: Ficha técnica AFINITOR 10 MG COMPRIMIDOS

ICD-10: C50 · ICD-11: 2C6Z

Renal cell carcinoma

Second line

Second-line for metastatic clear cell RCC after VEGF inhibitor progression (sunitinib, pazopanib) per ESMO 2024. Dose 10 mg once daily. RECORD-1 extended progression-free survival from 1.9 to 4.9 months.

Sources

ICD-10: C64 · ICD-11: 2C90.0

Transplant rejection prophylaxis

Second line

Everolimus is a second-line mTOR inhibitor for rejection prophylaxis after kidney, liver and heart transplantation. Combined with tacrolimus or ciclosporin at reduced doses to limit calcineurin nephrotoxicity. KDIGO 2024 recommends everolimus as an option in patients with prior malignancy due to its anticancer activity.

Sources

ICD-10: Z94 · ICD-11: QB63

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Anti-aging and longevity

Not recommended

Everolimus is an mTOR inhibitor. It is prescribed to prevent organ transplant rejection and for certain malignancies (renal cell carcinoma, pancreatic neuroendocrine tumors, HR+ HER2- metastatic breast cancer), and for tuberous sclerosis (AEMPS Ficha Técnica). In longevity communities, everolimus is actively promoted as an mTOR inhibitor for life extension, by analogy with rapamycin. The RESILIENT 2014 study in older adults showed transient improvement in vaccination response, but no randomized clinical trials with endpoints on lifespan extension in healthy adults exist. The drug has serious risks: immunosuppression with infections (including opportunistic), stomatitis (common), interstitial lung disease (life-threatening), hyperlipidemia, hyperglycemia, impaired wound healing, and thromboembolic events. If everolimus was recommended to a healthy person for longevity, seek a second opinion immediately.

Sources

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

A sirolimus derivative. Binds cytosolic FKBP-12; the complex inhibits mTORC1 – a key regulator of cell growth, proliferation, angiogenesis, and metabolism. Suppresses proliferation of activated T- and B-cells (immunosuppression) and tumor cells in sensitive cancers (RCC, ER+ HER2-negative breast cancer, neuroendocrine tumors). CYP3A4- and P-gp metabolized – numerous drug interactions.

Safety

Boxed warning

FDA boxed warning (transplant): increased mortality from infections and renal artery thrombosis when used in the early post-transplant period. Not used earlier than 30 days post-kidney and 70 days post-heart transplant.

Contraindications

Hypersensitivity to everolimus, sirolimus, or rapamycin derivatives
Active severe infections
Pregnancy and lactation

Serious adverse effects

Non-infectious pneumonitis (10–15%, sometimes fatal)
Serious infections including opportunistic
Type 2 diabetes
Acute kidney injury
Venous and arterial thromboembolism
Hepatitis B reactivation
Lymphoma and other secondary malignancies (long-term transplant use)

Common adverse effects

Stomatitis and oral ulcers
Rash and pruritus
Fatigue
Diarrhea
Nausea
Reduced appetite
Hyperglycemia and hyperlipidemia
Neutropenia and thrombocytopenia

Pregnancy: can you take Everolimus?

Contraindicated. Reliable contraception is required in women of reproductive age and in partners of male patients during therapy and for 8 weeks after.

Breastfeeding: can you take Everolimus?

Contraindicated during lactation.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Monitoring

Take once or twice daily at the same time with or without food – but always the same (bioavailability differs). Monitor everolimus blood level (target trough 3–8 ng/mL in transplant). Before start and regularly: CBC, lipid profile, glycemia, creatinine, proteinuria. Monitor for opportunistic infections (CMV, pneumocystis) and non-infectious pneumonitis.

Drug–nutrient interactions

Grapefruit juice

Everolimus depends on CYP3A4 and P-glycoprotein, and grapefruit juice inhibits both. The Afinitor SmPC cites no dedicated study but expects exposure to rise, with wide variation between people, and says to avoid the combination. Excess everolimus makes mouth ulcers, pneumonitis (dry cough, breathlessness), infections and raised glucose and lipids more likely.

Source: EMA: Ficha técnica de Afinitor 10 mg comprimidos (everolimus) (2025)

Drug–drug interactions

9 pairs found. Sorted from critical to minor.

CriticalClarithromycinMacrolide antibiotic

Mechanism

Clarithromycin inhibits CYP3A4 and P-gp. Everolimus rises 5+ fold – severe immunosuppression, pneumonitis, nephrotoxicity.

Symptoms

Dyspnoea, rising creatinine, cytopenia.

Management

Combination contraindicated. Alternative – azithromycin.

Sources

Pair details →Clarithromycin →

CriticalCobicistatPharmacokinetic enhancer (booster) for antiretroviral therapy

Mechanism

Cobicistat is a strong CYP3A4 inhibitor (similar to ritonavir). Everolimus rises 10+ fold.

Symptoms

Acute immunosuppression.

Management

Combination contraindicated.

Sources

Pair details →Cobicistat →

CriticalItraconazoleAntifungal, triazole

Mechanism

Strong CYP3A4 inhibitor – everolimus rises 9-fold. Certican Section 4.3 strict contraindication.

Symptoms

Acute immunosuppression, pneumonitis.

Management

Combination contraindicated.

Sources

Pair details →Itraconazole →

CriticalPosaconazoleSecond-generation systemic triazole antifungal

Mechanism

Strong CYP3A4 inhibitor. Everolimus rises 9-fold.

Symptoms

Immunosuppression, nephrotoxicity.

Management

Combination contraindicated.

Sources

Pair details →Posaconazole →

CriticalSirolimusSelective immunosuppressant, mTOR inhibitor

Mechanism

Both are mTOR inhibitors. Combined use produces dual blockade with severe immunosuppression and toxicity. No clinical indication for co-use.

Symptoms

Severe immunosuppression, infections, pneumonitis.

Management

Combination contraindicated.

Sources

Pair details →Sirolimus →

MajorHypericum perforatumAntidepressants. Other antidepressants of herbal origin

Mechanism

St. John's wort is a potent inducer of the CYP3A4 enzyme (and of CYP2C9 and P-glycoprotein). After 1–2 weeks it speeds up the breakdown of Everolimus and lowers its blood level, weakening its effect.

Symptoms

Reduced everolimus levels, loss of immunosuppressant or antitumor effect, risk of transplant rejection.

Management

Avoid the combination. Monitor everolimus levels and stop the herb.

Sources

Pair details →Hypericum perforatum →

MajorRifampicinAntituberculous antibiotic

Mechanism

Rifampicin is a strong CYP3A4 inducer. Everolimus falls 60% – transplant rejection risk.

Symptoms

Transplant rejection signs.

Management

Alternative TB regimen without rifampicin. If necessary – double everolimus with frequent blood level monitoring.

Sources

Pair details →Rifampicin →

MajorRitonavirHIV protease inhibitor / pharmacokinetic booster

Mechanism

Ritonavir is one of the strongest CYP3A4 inhibitors, and CYP3A4 clears everolimus. With ketoconazole, an inhibitor of the same strength, everolimus AUC rises 15-fold.

Symptoms

Acute nephrotoxicity, pneumonitis.

Management

The combination is not recommended. The European everolimus SmPCs for cancer and tuberous sclerosis () name ritonavir among strong CYP3A4 inhibitors and advise against the pair, as there are no data to guide dosing. The US cancer label () says to avoid it. After organ transplantation, the Spanish everolimus SmPC allows the pair only if the benefit outweighs the risk, and the US transplant label only with close monitoring of everolimus trough levels. In that case, adjust the dose to trough levels measured at least 4–5 days after the previous dose change (everolimus SmPC). The ritonavir label calls for careful monitoring of everolimus effect and adverse reactions.

Sources

Pair details →Ritonavir →

MajorVoriconazoleTriazole derivatives, systemic antifungals

Mechanism

Voriconazole strongly inhibits CYP3A4, the enzyme that clears everolimus. The pair has not been studied directly, but ketoconazole, an inhibitor of the same strength, raises everolimus AUC 15-fold.

Symptoms

Immunosuppression, nephrotoxicity.

Management

Both labels advise against the pair (AEMPS, ): there are no data to set an everolimus dose. For antifungal treatment, choose a drug that does not inhibit CYP3A4 this strongly. If voriconazole cannot be avoided, measure everolimus trough levels and adjust the dose to them.

Sources

Pair details →Voriconazole →

Label mentions50 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorACE inhibitorsclass named in the label
«Effects of Combination Use of Angiotensin Converting Enzyme (ACE) Inhibitors: Patients taking concomitant ACE inhibitors with Everolimus may be at increased risk for angioedema. Avoid the concomitant…»
FDA, section 7 · Open on DailyMed
MajorCYP3A4 inhibitorsclass named in the label
«DRUG INTERACTIONS: • Strong CYP3A inhibitor and P-gp inhibitor : Avoid coadministration. ( 2.11 , 7.1 )»
FDA, section 7 · Open on DailyMed
MajorErythromycin
«Eritromicina: Deberá tenerse precaución cuando no pueda evitarse la administración concomitante de inhibidores moderados de CYP3A4 o de PgP. Si los pacientes necesitan la administración conjunta de…»
AEMPS, section 4.5 · Open on CIMA
Majorinhibidores del CYP3A4class named in the label
«Eritromicina: Deberá tenerse precaución cuando no pueda evitarse la administración concomitante de inhibidores moderados de CYP3A4 o de PgP. Si los pacientes necesitan la administración conjunta de…»
AEMPS, section 4.5 · Open on CIMA
MajorKetoconazole
«Ketoconazol: No se recomienda el tratamiento concomitante de everolimus y de inhibidores potentes.»
AEMPS, section 4.5 · Open on CIMA
MajorRifampicin
«Rifampicina: Evitar el uso conjunto de inductores potentes de CYP3A4. Si los pacientes necesitan la administración conjunta de un inductor potente de CYP3A4, debe considerarse un aumento de la dosis…»
AEMPS, section 4.5 · Open on CIMA
ModerateCisapride
«Interacciones: Se debe tener precaución cuando se administre everolimus en combinación con sustratos de CYP3A4 administrados por vía oral con un estrecho margen terapéutico, debido a la posibilidad…»
AEMPS, section 4.4 · Open on CIMA
Moderatecorticosteroidesclass named in the label
«Estomatitis: En pacientes tratados con everolimus la estomatitis, incluyendo úlceras en la boca y mucositis bucal es la reacción adversa notificada de forma más frecuente (ver sección 4.8). La…»
AEMPS, section 4.4 · Open on CIMA
Moderateinductores del CYP3A4class named in the label
«Rifampicina: Evitar el uso conjunto de inductores potentes de CYP3A4. Si los pacientes necesitan la administración conjunta de un inductor potente de CYP3A4, debe considerarse un aumento de la dosis…»
AEMPS, section 4.5 · Open on CIMA
Moderateinmunosupresoresclass named in the label
«Infecciones: Se han notificado casos de NPJ, NPC, algunos con desenlace mortal, en pacientes que recibieron everolimus. La NPJ/NPC se puede asociar con el uso concomitante de corticosteroides u otros…»
AEMPS, section 4.4 · Open on CIMA
ModeratePimozide
«Interacciones: Se debe tener precaución cuando se administre everolimus en combinación con sustratos de CYP3A4 administrados por vía oral con un estrecho margen terapéutico, debido a la posibilidad…»
AEMPS, section 4.4 · Open on CIMA
ModerateQuinidine
«Interacciones: Se debe tener precaución cuando se administre everolimus en combinación con sustratos de CYP3A4 administrados por vía oral con un estrecho margen terapéutico, debido a la posibilidad…»
AEMPS, section 4.4 · Open on CIMA
Carbamazepine
«Carbamazepina, fenobarbital, fenitoína: No estudiados. Se espera una disminución en la exposición.»
AEMPS, section 4.5 · Open on CIMA
Ciclosporin
«Ciclosporina oral: AUC ↑2,7- veces (intervalo 1,5-4,7) C max ↑1,8- veces (intervalo 1,3-2,6)»
AEMPS, section 4.5 · Open on CIMA
CYP3A4 inducersclass named in the label
«DRUG INTERACTIONS: • Strong CYP3A inducer and P-gp inducer : Increase the dosage as recommended. ( 2.11 , 7.1 )»
FDA, section 7 · Open on DailyMed
Dexamethasone
«Dexametasona: No estudiados. Se espera una disminución en la exposición.»
AEMPS, section 4.5 · Open on CIMA
Dronedarone
«Dronedarona: No estudiados. Se espera un aumento en la exposición.»
AEMPS, section 4.5 · Open on CIMA
Efavirenz
«Efavirenz, nevirapina: No estudiados. Se espera una disminución en la exposición.»
AEMPS, section 4.5 · Open on CIMA
Estradiol
«Agentes a los que everolimus puede alterar su concentración plasmática: 45% y un 64% respectivamente. Sin embargo, los correspondientes niveles de estradiol en el estado estacionario (4 semanas) no…»
AEMPS, section 4.5 · Open on CIMA
Fluconazole
«Fluconazol: No estudiados. Se espera un aumento en la exposición.»
AEMPS, section 4.5 · Open on CIMA
inhibidores de la ECAclass named in the label
«Uso concomitante de inhibidores de la enzima convertidora de angiotensina (ECA): Los pacientes que toman de forma concomitante un inhibidor de la ECA (p.ej. ramipril) pueden tener un mayor riesgo de…»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

MajorDarunavir
«ANTINEOPLÁSICOS: Las concentraciones de estos medicamentos pueden aumentar cuando se administran al mismo tiempo que darunavir potenciado, con la consiguiente posibilidad de que aumenten los…»
AEMPS, section 4.5 · Open on CIMA
MajorDarunavir
«Established and Other Potentially Significant Drug Interactions: Immunosuppressants : e.g. cyclosporine, tacrolimus, sirolimus Immunosuppressant/neoplastic: everolimus irinotecan …»
FDA, section 7 · Open on DailyMed
MajorVoriconazole
«[sustratos del CYP3A4]: No se recomienda la administraci ó n concomitante de voriconazol y everolimus, ya que se espera que voriconazol incremente significativamente las concentraciones de everolimus…»
AEMPS, section 4.5 · Open on CIMA
MajorVoriconazole
«DRUG INTERACTIONS: Everolimus (CYP3A4 Inhibition) Not Studied In Vivo or In Vitro , but Drug Plasma Exposure Likely to be Increased Concomitant administration of voriconazole and everolimus is not…»
FDA, section 7 · Open on DailyMed
ModerateCiclosporin
«Número de veces que cambia la exposición con ciclosporina: Se observaron elevaciones de la creatinina sérica en los estudios en los que se utilizaba everolimus o sirolimus en combinación con dosis…»
AEMPS, section 4.5 · Open on CIMA
ModerateCobicistat
«Established and Other Potentially Significant Interactions: Immuno-suppressants: cyclosporine everolimus sirolimus tacrolimus ↑ immuno-suppressants These immunosuppressant agents are metabolized by…»
FDA, section 7 · Open on DailyMed
ModerateDiltiazem
«Inhibidores de la diana de Rapamicina en las células de mamífero (mTOR): la Cmax y el AUC de sirolimus (sustrato del CYP3A4) aumentaron 1,4 y 1,6 veces, respectivamente, tras la administración oral…»
AEMPS, section 4.5 · Open on CIMA
ModerateDronedarone
«Interacción con medicamentos que son metabolizados por el CYP 3A4: Dronedarona podría aumentar las concentraciones plasmáticas de inmunosupresores (tacrolimus, sirolimus, everolimus y ciclosporina)…»
AEMPS, section 4.5 · Open on CIMA
ModerateLisinopril
«Hipersensibilidad/Angioedema: El uso concomitante de IECA con racecadotrilo, inhibidores de mTOR (por ejemplo, sirólimus, everólimus, temsirólimus) y vildagliptina puede aumentar el riesgo de…»
AEMPS, section 4.4 · Open on CIMA
ModerateRamipril
«Inhibidores de mTOR o vildagliptina: Es posible que se produzca un aumento del riesgo de angioedema en pacientes que toman medicamentos concomitantes como inhibidores de mTOR (p. ej. temsirolimus…»
AEMPS, section 4.5 · Open on CIMA
ModerateRanolazine
«La ranolazina es un inhibidor de moderado a potente de la P-gp y un inhibidor débil del CYP3A4, y puede elevar las concentraciones plasmáticas de sustratos de la P-gp o del CYP3A4. La distribución…»
AEMPS, section 4.5 · Open on CIMA
ModerateRitonavir
«Inmunosupresores: Ritonavir dosificado como potenciador farmacocinético o agente antirretroviral inhibe CYP3A4 y resulta esperable el aumento de las concentraciones plasmáticas de ciclosporina…»
AEMPS, section 4.5 · Open on CIMA
ModerateRupatadine
«Puede requerirse el ajuste de la dosis de sustratos susceptibles del CYP3A4 (p. ej., simvastatina, lovastatina) y sustratos del CYP3A4 con estrecho índice terapéutico (p. ej., ciclosporina…»
AEMPS, section 4.4 · Open on CIMA
ModerateVerapamil
«Puede ser necesario determinar las concentraciones y ajustar la dosis de everolimus»
AEMPS, section 4.5 · Open on CIMA
Amlodipine
«Los inhibidores de mTOR como, por ejemplo, sirolimus, temsirolimus y everolimus son sustratos del CYP3A. El amlodipino es un inhibidor débil del CYP3A. Con el uso concomitante de inhibidores de mTOR…»
AEMPS, section 4.5 · Open on CIMA
Carbamazepine
«Fármacos que pueden disminuir los niveles plasmáticos de carbamazepina: Inmunosupresores: ciclosporina, everolimus, tacrolimus, sirolimus.»
AEMPS, section 4.5 · Open on CIMA
Enalapril
«Inhibidores de la diana de la rapamicina (mTOR) en los mamíferos: Los pacientes en tratamiento concomitante con inhibidores de mTOR (p. ej. temsirolimus, sirolimus, everolimus) pueden tener un mayor…»
AEMPS, section 4.5 · Open on CIMA
Enalapril
«mTOR (Mammalian Target of Rapamycin) Inhibitors: Patients receiving coadministration of ACE inhibitor and mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk…»
FDA, section 7 · Open on DailyMed
Fluconazole
«Inmunosupresores (p. ej.: ciclosporina, everolimus, sirolimus y tacrolimus): Tacrolimus: Fluconazol puede incrementar hasta 5 veces la concentración sérica de tacrolimus administrado por vía oral…»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Everolimus used for?

Everolimus is evaluated for the following indications with varying evidence strength: Transplant rejection prophylaxis (evidence tier A), Renal cell carcinoma (evidence tier A), ER-positive breast cancer (evidence tier A). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Everolimus?

Common side effects of Everolimus (≥ 1 in 100): Stomatitis and oral ulcers, Rash and pruritus, Fatigue, Diarrhea, Nausea, Reduced appetite. See the Safety section for uncommon and serious reactions.

Is Everolimus safe during pregnancy?

Contraindicated. Reliable contraception is required in women of reproductive age and in partners of male patients during therapy and for 8 weeks after.

Is Everolimus compatible with breastfeeding?

Contraindicated during lactation.

Who should not take Everolimus?

Everolimus is contraindicated in: Hypersensitivity to everolimus, sirolimus, or rapamycin derivatives; Active severe infections; Pregnancy and lactation. Full list in the Safety section.

Does Everolimus carry an FDA boxed warning?

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 09/20/2024
EMALabel dated 09/02/2011
FDA / DailyMedLabel dated 08/14/2026

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