Everolimus: Difference between revisions

{{Short description|Chemical compound}}

{{Use dmy dates|date=December 2021}}

{{Infobox drug

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| verifiedrevid = 459441923

| image = Everolimus.svg

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| image2 = Everolimus ball-and-stick.png

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<!-- Clinical data -->

| pronounce = Everolimus {{IPAc-en|ˌ|ɛ|v|ə|ˈ|r|oʊ|l|ə|m|ə|s}}

| tradename = Afinitor, Zortress

| Drugs.com = {{drugs.com|monograph|everolimus}}

| MedlinePlus = a609032

| DailyMedID = Everolimus

| pregnancy_AU = C

| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{drugs.com|pregnancy|everolimus}}</ref>

| pregnancy_category =

| routes_of_administration = [[Oral administration|By mouth]]

| class =

| ATC_prefix = L01

| ATC_suffix = EG02

| ATC_supplemental = {{ATC|L04|AH02}}

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

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| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment = <ref>{{cite web | title=Summary of Product Characteristics (SmPC) - (emc) | website=Certican Tablets | date=15 January 2021 | url=https://www.medicines.org.uk/emc/product/1920/smpc | access-date=30 December 2021}}</ref>

| legal_US = Rx-only

| legal_US_comment = <ref name="Afinitor FDA label">{{cite web | title=Afinitor- everolimus tablet Afinitor Disperz- everolimus tablet, for suspension | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2150f73a-179b-4afc-b8ce-67c85cc72f04 | access-date=30 December 2021}}</ref><ref name="Zortress FDA label">{{cite web | title=Zortress- everolimus tablet | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e082a024-7850-400b-a5c2-2a140612562a | access-date=30 December 2021}}</ref>

| legal_EU = Rx-only

| legal_EU_comment = <ref name="Afinitor EPAR">{{cite web | title=Afinitor EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/afinitor | access-date=30 December 2021}}</ref><ref name="Votubia EPAR">{{cite web | title=Votubia EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/votubia | access-date=30 December 2021}}</ref>

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = Rx-only

<!-- Pharmacokinetic data -->

| bioavailability =

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life = ~30 hours<ref>{{cite journal | vauthors = Formica RN, Lorber KM, Friedman AL, Bia MJ, Lakkis F, Smith JD, Lorber MI | title = The evolving experience using everolimus in clinical transplantation | journal = Transplantation Proceedings | volume = 36 | issue = 2 Suppl | pages = 495S–499S | date = March 2004 | pmid = 15041395 | doi = 10.1016/j.transproceed.2004.01.015 }}</ref>

| duration_of_action =

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<!-- Identifiers -->

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 159351-69-6

| CAS_supplemental =

| PubChem = 6442177

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| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01590

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 21106307

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D02714

| ChEBI_Ref =

| ChEBI = 68478

| ChEMBL = 1908360

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = <small>42-''O''-(2-hydroxyethyl)rapamycin</small>, RAD001

<!-- Chemical and physical data -->

| IUPAC_name = Dihydroxy-12-[(2''R'')-1-[(1''S'',3''R'',4''R'')-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0 hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone

| C = 53 | H = 83 | N = 1 | O = 14

| SMILES = OCCO[C@@H]1CC[C@H](C[C@H]1OC)C[C@@H](C)[C@@H]4CC(=O)[C@H](C)/C=C(\C)[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(/C)[C@@H](OC)C[C@@H]2CC[C@@H](C)[C@@](O)(O2)C(=O)C(=O)N3CCCC[C@H]3C(=O)O4

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'''Everolimus''', sold under the brand name '''Afinitor''' among others, is a [[medication]] used as an [[Immunosuppression|immunosuppressant]] to prevent [[Transplant rejection|rejection]] of [[organ transplant]]s<ref name="Tedesco-Silva_2022">{{cite journal | vauthors = Tedesco-Silva H, Saliba F, Barten MJ, De Simone P, Potena L, Gottlieb J, Gawai A, Bernhardt P, Pascual J | display-authors = 6 | title = An overview of the efficacy and safety of everolimus in adult solid organ transplant recipients | journal = Transplantation Reviews | volume = 36 | issue = 1 | pages = 100655 | date = January 2022 | pmid = 34696930 | doi = 10.1016/j.trre.2021.100655 | s2cid = 239887236 | hdl = 10230/53730 | hdl-access = free }}</ref> and as a [[targeted therapy]] in the treatment of renal cell cancer and other tumours.<ref name="Hasskarl_2018">{{cite book | vauthors = Hasskarl J | title = Small Molecules in Oncology | chapter = Everolimus | journal = Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer | series = Recent Results in Cancer Research | volume = 211 | issue = | pages = 101–123 | date = 2018 | pmid = 30069763 | doi = 10.1007/978-3-319-91442-8_8 | isbn = 978-3-319-91441-1 }}</ref>

This compound also has a use in cardiovascular [[drug-eluting stent]] technologies to inhibit [[restenosis]].{{medcn|date=December 2023}}

It is the 40-''O''-(2-hydroxyethyl) derivative of [[sirolimus]] and works similarly to sirolimus as an inhibitor of [[mammalian target of rapamycin]] (mTOR).<ref>{{cite book | vauthors = Hasskarl J | chapter = Everolimus | veditors = Martens UM |title=Small Molecules in Oncology |date=2018 |publisher=Springer |location=Heidelberg |isbn=978-3-319-91442-8 |page=101-124 |edition=Third | chapter-url=https://books.google.com/books?id=XhdnDwAAQBAJ&dq=Everolimus+mtor+inhibitor+mechanism+of+action+structure&pg=PR6 }}</ref>

It is marketed by [[Novartis]] under the trade names Zortress (US) and Certican (European Union and other countries) in transplantation medicine, and as Afinitor (general tumours) and Votubia (tumours as a result of [[Tuberous Sclerosis Complex]] (TSC)) in oncology.{{citation needed|date=December 2021}}

It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref>{{cite web | title=First Generic Drug Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=15 November 2021 | url=https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals | access-date=30 December 2021}}</ref>

==Medical uses==

* Advanced kidney cancer (US FDA approved in March 2009)<ref>{{cite press release | title = Afinitor approved in US as first treatment for patients with advanced kidney cancer after failure of either sunitinib or sorafenib | publisher = [[Novartis]] | date = 30 March 2009 | url = http://www.novartis.com/newsroom/media-releases/en/2009/1301801.shtml | access-date = 6 April 2009 | archive-date = 3 April 2009 | archive-url = https://web.archive.org/web/20090403071403/http://www.novartis.com/newsroom/media-releases/en/2009/1301801.shtml | url-status = dead }}</ref>

* Prevention of organ rejection after renal transplant(US FDA April 2010)<ref>{{cite press release | title = Novartis receives US FDA approval for Zortress (everolimus) to prevent organ rejection in adult kidney transplant recipients | publisher = [[Novartis]] | date = 22 April 2010 | url = http://www.novartis.com/newsroom/media-releases/en/2010/1406625.shtml | access-date = 26 April 2010 | archive-url = https://web.archive.org/web/20100425204743/http://www.novartis.com/newsroom/media-releases/en/2010/1406625.shtml | archive-date = 25 April 2010 | url-status = dead }}</ref>

* [[subependymal giant cell astrocytoma|Subependymal giant cell astrocytoma (SEGA)]] associated with [[tuberous sclerosis|tuberous sclerosis (TS)]] in patients who are not suitable for surgical intervention (US FDA October 2010)<ref name="GenNews_2010">{{cite news |url=http://www.genengnews.com/gen-news-highlights/novartis-afinitor-cleared-by-fda-for-treating-sega-tumors-in-tuberous-sclerosis/81244159/ |title=Novartis' Afinitor Cleared by FDA for Treating SEGA Tumors in Tuberous Sclerosis |date=1 November 2010 | work = Genetic Engineering & Biotechnology News }}</ref>

* Progressive or metastatic [[pancreatic neuroendocrine tumor]]s not surgically removable (May 2011)<ref>{{cite web | title = FDA approves new treatment for rare type of pancreatic cancer | date = 6 May 2011 | publisher = U.S. Food and Drug Administration (FDA) | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm254350.htm | archive-url = https://web.archive.org/web/20140801134256/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm254350.htm | archive-date = 1 August 2014 }}</ref>

* Breast cancer in post-menopausal women with advanced hormone-receptor positive, HER2-negative type cancer, in conjunction with [[exemestane]] (US FDA July 2012)<ref name=July2012>{{cite news |url=https://www.reuters.com/article/novartis-afinitor-idUSL2E8IKD8B20120720 |title=US FDA approves Novartis drug Afinitor for breast cancer |date=20 July 2012 | work=Reuters}}</ref>

* Prevention of organ rejection after liver transplant(Feb 2013)

* Progressive, well-differentiated non-functional, [[neuroendocrine tumor]]s (NET) of gastrointestinal (GI) or lung origin with unresectable, locally advanced or metastatic disease (US FDA February 2016).<ref name=NET-2016>{{cite web | url = https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm488028.htm | title = Everolimus (Afinitor) | date = February 2016 | work = U.S. Food and Drug Administration }}</ref>

* [[Tuberous sclerosis complex]]-associated partial-onset seizures for adult and pediatric patients aged 2 years and older. (US FDA April 2018).<ref name="NET -2018">{{cite web | title=FDA approves everolimus for tuberous sclerosis complex-associated | website=U.S. Food and Drug Administration | date=3 November 2018 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-everolimus-tuberous-sclerosis-complex-associated-partial-onset-seizures | access-date=30 December 2021}}</ref>

==UK National Health Service==

[[NHS England]] has been criticised for delays in deciding on a policy for the prescription of everolimus in the treatment of [[Tuberous Sclerosis]]. 20 doctors addressed a letter to the board in support of the charity Tuberous Sclerosis Association saying " around 32 patients with critical need, whose doctors believe everolimus treatment is their best or only option, have no hope of access to funding. Most have been waiting many months. Approximately half of these patients are at imminent risk of a catastrophic event (renal bleed or kidney failure) with a high risk of preventable death."<ref>{{cite news| vauthors = Lintern S |title=Policy delays risk 'preventable deaths', doctors warn NHS England|url=http://www.hsj.co.uk/news/policy-delays-risk-preventable-deaths-doctors-warn-nhs-england/5084158.article |access-date=20 April 2015|publisher=Health Service Journal|date=14 April 2015}}</ref> In May 2015 it was reported that Luke Henry and Stephanie Rudwick, the parents of a child suffering from Tuberous Sclerosis were trying to sell their home in Brighton to raise £30,000 to pay for treatment for their daughter Bethany who has tumours on her brain, kidneys and liver and suffers from up to 50 epileptic fits a day.<ref>{{cite news|title=Couple forced to sell home after NHS refuse to fund daughter's treatment for rare illness|url=http://www.express.co.uk/news/uk/576462/Brighton-home-sell-sick-child|access-date=12 May 2015|publisher=Daily Express|date=11 May 2015}}</ref>

{{As of|2010|10}}, Phase III trials are under way in [[gastric cancer]], [[hepatocellular carcinoma]], and [[lymphoma]].<ref name="GenNews_2010" /> The experimental use of everolimus in refractory [[Graft-versus-host disease|chronic graft-versus-host disease]] was reported in 2012.<ref>{{cite journal |vauthors=Lutz M, Kapp M, Grigoleit GU, Stuhler G, Einsele H, Mielke S |title=Salvage therapy with everolimus improves quality of life in patients with refractory chronic graft-versus-host disease |journal=[[Bone Marrow Transplantation (journal)|Bone Marrow Transplant]] |volume=47 |issue=S1 |pages=S410–S411 |date=April 2012 |url=http://www.nature.com/bmt/journal/v47/n1s/pdf/bmt201237a.pdf}}</ref>

Interim phase III trial results in 2011, showed that adding Afinitor (everolimus) to [[exemestane]] therapy against advanced breast cancer can significantly improve [[progression-free survival]] compared with exemestane therapy alone.<ref>{{cite news |url=http://www.genengnews.com/gen-news-highlights/positive-trial-data-leads-novartis-to-plan-breast-cancer-filing-for-afinitor-by-year-end/81245384/ |title=Positive Trial Data Leads Novartis to Plan Breast Cancer Filing for Afinitor by Year End |year=2011 }}</ref>

A study published in 2012, shows that everolimus sensitivity varies between patients depending on their tumor genomes.<ref>{{cite journal | vauthors = Iyer G, Hanrahan AJ, Milowsky MI, Al-Ahmadie H, Scott SN, Janakiraman M, Pirun M, Sander C, Socci ND, Ostrovnaya I, Viale A, Heguy A, Peng L, Chan TA, Bochner B, Bajorin DF, Berger MF, Taylor BS, Solit DB | title = Genome sequencing identifies a basis for everolimus sensitivity | journal = Science | volume = 338 | issue = 6104 | pages = 221 | date = October 2012 | pmid = 22923433 | pmc = 3633467 | doi = 10.1126/science.1226344 | bibcode = 2012Sci...338..221I }}</ref> A group of patients with advanced metastasic bladder carcinoma <ref>{{ClinicalTrialsGov|NCT00805129|Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium}}</ref> treated with everolimus revealed a single patient who had a complete response to everolimus treatment for 26 months. The researchers sequenced the genome of this patient and compared it to different reference genomes and to other patients' genomes. They found that mutations in TSC1 led to a lengthened duration of response to everolimus and to an increase in the time to cancer recurrence. The mutated TSC1 apparently had made these tumors vulnerable to treatment with everolimus.{{medcn|date=August 2020}}

A [[Phases of clinical research#Phase II|phase IIa]] randomized, placebo-controlled everolimus clinical trial published in 2014 showed that everolimus improved the response to an [[influenza vaccine]] by 20% in healthy elderly volunteers.<ref name="pmid32229705">{{cite journal | author=Zhavoronkov A | title=Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections | journal=[[Aging (journal)|Aging]] | volume=12 | issue=8 | pages=6492–6510 | year=2020 | doi =10.18632/aging.102988 | pmc=7202545 | pmid=32229705}}</ref> A phase IIa randomized, placebo-controlled clinical trial published in 2018 showed that everolimus in combination with [[dactolisib]] decreased the rate of reported infections in an elderly population.<ref name="pmid32229705" />

Compared with the parent compound [[rapamycin]], everolimus is more water-soluble.<ref name="pmid31817676">{{cite journal | vauthors=Magaway C, Kim E, Jacinto E | title=Targeting mTOR and Metabolism in Cancer: Lessons and Innovations | journal=Cells | volume=8 | issue=12 | pages=1584 | year=2019 | doi =10.3390/cells8121584 | pmc=6952948 | pmid=31817676| doi-access=free }}</ref> Compared to rapamycin, everolimus is more selective for the [[mTORC1]] protein complex, with little impact on the [[mTORC2]] complex.<ref name=ArriolaApelo>{{cite journal | vauthors = Arriola Apelo SI, Neuman JC, Baar EL, Syed FA, Cummings NE, Brar HK, Pumper CP, Kimple ME, Lamming DW | title = Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system | journal = Aging Cell | volume = 15 | issue = 1 | pages = 28–38 | date = February 2016 | pmid = 26463117 | pmc = 4717280 | doi = 10.1111/acel.12405 }}</ref> This can lead to a hyper-activation of the kinase [[AKT]] via inhibition on the mTORC1 [[negative feedback]] loop, while not inhibiting the mTORC2 positive feedback to AKT. This AKT elevation can lead to longer survival in some cell types.{{medcn|date=August 2020}} Thus, everolimus has important effects on cell growth, cell proliferation and cell survival.

mTORC1 inhibition by everolimus has been shown to normalize tumor blood vessels, to increase [[tumor-infiltrating lymphocytes]], and to improve [[Adoptive cell transfer|adoptive cell transfer therapy]].<ref name="pmid32759497">{{cite journal | vauthors=Wang S, Raybuck A, Shiuan E, Jin J | title=Selective inhibition of mTORC1 in tumor vessels increases antitumor immunity | journal= [[JCI Insight]] | volume=5 | issue=15 | pages=e139237 | year=2020 | doi =10.1172/jci.insight.139237 | pmc=7455083 | pmid=32759497}}</ref>

Additionally, mTORC2 is believed to play an important role in glucose metabolism and the immune system, suggesting that selective inhibition of mTORC1 by drugs such as everolimus could achieve many of the benefits of rapamycin without the associated [[glucose intolerance]] and [[immunosuppression]].<ref name=ArriolaApelo/>

[[TSC1]] and [[TSC2]], the genes involved in [[tuberous sclerosis]], act as tumor suppressor genes by regulating mTORC1 activity. Thus, either the loss or inactivation of one of these genes lead to the activation of mTORC1.<ref name="novartis.com.au">{{Cite web |url=http://www.novartis.com.au/DownloadFile.aspx?t=p&f=afi.pdf&dateid=1343206022000 |title=AFINITOR (everolimus)| publisher = Novartis |access-date=26 February 2014 |archive-url=https://web.archive.org/web/20140308141850/http://www.novartis.com.au/DownloadFile.aspx?t=p&f=afi.pdf&dateid=1343206022000 |archive-date=8 March 2014 |url-status=dead }}</ref>

Everolimus binds to its protein receptor [[FKBP12]], which directly interacts with mTORC1, inhibiting its downstream signaling. As a consequence, mRNAs that code for proteins implicated in the cell cycle and in the glycolysis process are impaired or altered, and tumor growth is inhibited.<ref name="novartis.com.au"/>

==Adverse reactions==

A trial using 10&nbsp;mg/day in patients with NETs of GI or lung origin reported "Everolimus was discontinued for adverse reactions in 29% of patients and dose reduction or delay was required in 70% of everolimus-treated patients. Serious adverse reactions occurred in 42% of everolimus-treated patients and included 3 fatal events (cardiac failure, respiratory failure, and septic shock). The most common adverse reactions (incidence greater than or equal to 30%) were stomatitis, infections, diarrhea, peripheral edema, fatigue and rash. The most common blood abnormalities found (incidence greater than or equal to 50%) were anemia, hypercholesterolemia, lymphopenia, elevated aspartate transaminase (AST) and fasting hyperglycemia.".<ref name=NET-2016/>

Everolimus may have a role in heart transplantation, as it has been shown to reduce [[cardiac allograft vasculopathy|chronic allograft vasculopathy]] in such transplants. It also may have a similar role to sirolimus in kidney and other transplants.<ref name="pmid12944570">{{cite journal | vauthors = Eisen HJ, Tuzcu EM, Dorent R, Kobashigawa J, Mancini D, Valantine-von Kaeppler HA, Starling RC, Sørensen K, Hummel M, Lind JM, Abeywickrama KH, Bernhardt P | title = Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients | journal = The New England Journal of Medicine | volume = 349 | issue = 9 | pages = 847–58 | date = August 2003 | pmid = 12944570 | doi = 10.1056/NEJMoa022171 | doi-access = free }}</ref>

==Role in liver transplantation==

Although, sirolimus had generated fears over use of m-TOR inhibitors in liver transplantation recipients, due to possible early hepatic artery thrombosis and graft loss, use of everolimus in the setting of liver transplantation is promising. Jeng et al.,<ref name="PMID 24767339">{{cite journal | vauthors = Jeng LB, Thorat A, Hsieh YW, Yang HR, Yeh CC, Chen TH, Hsu SC, Hsu CH | title = Experience of using everolimus in the early stage of living donor liver transplantation | journal = Transplantation Proceedings | volume = 46 | issue = 3 | pages = 744–8 | date = April 2014 | pmid = 24767339 | doi = 10.1016/j.transproceed.2013.11.068 }}</ref> in their study of 43 patients, concluded the safety of everolimus in the early phase after living donor liver transplantation. In their study, no hepatic artery thrombosis or wound infection was noted. Also, a possible role of everolimus in reducing the recurrence of hepatocellular carcinoma after liver transplantation was correlated. A target trough level of 3&nbsp;ng/mL at 3 months was shown to be beneficial in recipients with pre-transplant renal dysfunction. In their study, 6 of 9 renal failure patients showed significant recovery of renal function, whereas 3 showed further deterioration, one of whom required hemodialysis.<ref>{{cite journal | vauthors = Jeng L, Thorat A, Yang H, Yeh CC, Chen TH, Hsu SC | title = Impact of Everolimus On the Hepatocellular Carcinoma Recurrence After Living Donor Liver Transplantation When Used in Early Stage: A Single Center Prospective Study | journal = American Journal of Transplantation | date = 2015 | volume = 15 | issue = suppl 3 | url = http://www.atcmeetingabstracts.com/abstract/impact-of-everolimus-on-the-hepatocellular-carcinoma-recurrence-after-living-donor-liver-transplantation-when-used-in-early-stage-a-single-center-prospective-study/ }}</ref> A positive impact on hepatocellular carcinoma (HCC) was observed when everolimus was used as primary immunosuppression starting as early as first week after living donor liver transplantation (LDLT) surgery.<ref>{{cite journal | vauthors = Thorat A, Jeng LB, Yang HR, Yeh CC, Hsu SC, Chen TH, Poon KS | title = Assessing the role of everolimus in reducing hepatocellular carcinoma recurrence after living donor liver transplantation for patients within the UCSF criteria: re-inventing the role of mammalian target of rapamycin inhibitors | journal = Annals of Hepato-Biliary-Pancreatic Surgery | volume = 21 | issue = 4 | pages = 205–211 | date = November 2017 | pmid = 29264583 | pmc = 5736740 | doi = 10.14701/ahbps.2017.21.4.205 }}</ref>

Everolimus is used in [[drug-eluting stent|drug-eluting coronary stents]] as an immunosuppressant to prevent [[restenosis]]. Abbott Vascular produce an everolimus-eluting stent (EES) called Xience Alpine. It utilizes the Multi-Link Vision cobalt chromium stent platform and Novartis' everolimus. The product is widely available globally including the US, the European Union, and [[Asia-Pacific]] (APAC) countries. Boston Scientific also market EESes, recent offerings being Promus Elite and Synergy.{{citation needed|date=August 2020}}

== Use in aging ==

Inhibition of [[Mechanistic target of rapamycin|mTOR]], the molecular target of everolimus, extends the lifespan of model organisms including mice,<ref>{{cite journal | vauthors = Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA | title = Rapamycin fed late in life extends lifespan in genetically heterogeneous mice | journal = Nature | volume = 460 | issue = 7253 | pages = 392–5 | date = July 2009 | pmid = 19587680 | pmc = 2786175 | doi = 10.1038/nature08221 | bibcode = 2009Natur.460..392H }}</ref> and mTOR inhibition has been suggested as an anti-aging therapy. Everolimus was used in a clinical trial by Novartis, and short-term treatment was shown to enhance the response to the influenza vaccine in the elderly, possible by reversing [[immunosenescence]].<ref>{{cite journal | vauthors = Mannick JB, Del Giudice G, Lattanzi M, Valiante NM, Praestgaard J, Huang B, Lonetto MA, Maecker HT, Kovarik J, Carson S, Glass DJ, Klickstein LB | title = mTOR inhibition improves immune function in the elderly | journal = Science Translational Medicine | volume = 6 | issue = 268 | pages = 268ra179 | date = December 2014 | pmid = 25540326 | doi = 10.1126/scitranslmed.3009892 | s2cid = 206685475 }}</ref> Everolimus treatment of mice results in reduced metabolic side effects compared to [[sirolimus]].<ref name=ArriolaApelo/>

== References ==

{{Reflist}}

== Further reading ==

* {{cite journal | vauthors = Sedrani R, Cottens S, Kallen J, Schuler W | title = Chemical modification of rapamycin: the discovery of SDZ RAD | journal = Transplantation Proceedings | volume = 30 | issue = 5 | pages = 2192–4 | date = August 1998 | pmid = 9723437 | doi = 10.1016/S0041-1345(98)00587-9 }}

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