Difference between revisions of "Everolimus (Afinitor)"
m (Text replacement - "[[Media:" to "[[File:") |
m (Text replacement - "[[File:" to "[[:File:") |
||
Line 1: | Line 1: | ||
==General information== | ==General information== | ||
− | Class/mechanism: mTOR kinase inhibitor; mTOR (mammalian target of rapamycin) is a serine-threonine kinase downstream of the PI3K/AKT pathway. In vitro, everolimus has been found to reduce cell proliferation, angiogenesis, and glucose uptake. Everolimus forms inhibitory complexes with mTORC1 by binding to the intracellular protein FKBP-12. Reduces activity of downstream effectors of mTOR that are involved in protein synthesis, S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E binding protein (4E-BP1). Reduces expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1).<ref name="insert">[http://www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf Everolimus (Afinitor) package insert]</ref><ref>[[File:Everolimus.pdf | Everolimus (Afinitor) package insert (locally hosted backup)]]</ref><ref>[http://www.afinitor.com Afinitor manufacturer's website]</ref> | + | Class/mechanism: mTOR kinase inhibitor; mTOR (mammalian target of rapamycin) is a serine-threonine kinase downstream of the PI3K/AKT pathway. In vitro, everolimus has been found to reduce cell proliferation, angiogenesis, and glucose uptake. Everolimus forms inhibitory complexes with mTORC1 by binding to the intracellular protein FKBP-12. Reduces activity of downstream effectors of mTOR that are involved in protein synthesis, S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E binding protein (4E-BP1). Reduces expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1).<ref name="insert">[http://www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf Everolimus (Afinitor) package insert]</ref><ref>[[:File:Everolimus.pdf | Everolimus (Afinitor) package insert (locally hosted backup)]]</ref><ref>[http://www.afinitor.com Afinitor manufacturer's website]</ref> |
<br>Route: PO | <br>Route: PO | ||
<br>Extravasation: n/a | <br>Extravasation: n/a |
Revision as of 03:11, 20 September 2021
General information
Class/mechanism: mTOR kinase inhibitor; mTOR (mammalian target of rapamycin) is a serine-threonine kinase downstream of the PI3K/AKT pathway. In vitro, everolimus has been found to reduce cell proliferation, angiogenesis, and glucose uptake. Everolimus forms inhibitory complexes with mTORC1 by binding to the intracellular protein FKBP-12. Reduces activity of downstream effectors of mTOR that are involved in protein synthesis, S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E binding protein (4E-BP1). Reduces expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1).[1][2][3]
Route: PO
Extravasation: n/a
- Anecdotally, taking the pill in a small amount of whipped/sour cream[4] or putting the pill in a marshmallow[5] may decrease the likelihood of developing stomatitis/mucositis.
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]
Diseases for which it is used
- B-cell acute lymphoblastic leukemia
- HR+ Breast cancer
- Diffuse large B-cell lymphoma
- Hodgkin lymphoma
- Mantle cell lymphoma
- Neuroendocrine tumor
- Pancreatic NET
- Peripheral T-cell lymphoma
- Renal cell carcinoma
- Thymoma
- Waldenström macroglobulinemia
Patient drug information
- Everolimus (Afinitor) package insert[1]
- Everolimus (Afinitor) patient drug information (Chemocare)[6]
- Everolimus (Afinitor) patient drug information (UpToDate)[7]
History of changes in FDA indication
HR+ Breast cancer
- 7/20/2012: Approval expanded to include postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole. (Based on BOLERO-2)
Neuroendocrine tumor
- 2/26/2016: Approval expanded for the treatment of adult patients with progressive, well-differentiated non-functional, neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin with unresectable, locally advanced or metastatic disease. (Based on RADIANT-4)
Pancreatic NET
- 5/5/2011: Approval expanded to include progressive neuroendocrine tumors of pancreatic origin (PNET) that is unresectable, locally advanced or metastatic. (Based on RADIANT-3)
Renal cell carcinoma
- 3/30/2009: Initial FDA approval for the treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib. (Based on RECORD-1)
Tuberous sclerosis complex-associated renal angiomyolipoma
- 4/26/2012: Approval expanded to include adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. (Based on EXIST-2)
Tuberous sclerosis complex-associated subependymal giant cell astrocytoma
- 10/29/2010: Approval expanded to include subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection. (Based on EXIST-1 and Study 2485)
Also known as
- Code names: RAD001, RAD-001
- Brand names: Advacan, Afinitor, Afinitor Disperz, Certican, Everecan, EverGraf, Evermil, Evertor, Rapact, Rolimus, Votubia, Zortress
References
- ↑ 1.0 1.1 1.2 Everolimus (Afinitor) package insert
- ↑ Everolimus (Afinitor) package insert (locally hosted backup)
- ↑ Afinitor manufacturer's website
- ↑ Discussion between Sara Hurvitz, MD and Neil Love, MD, 2012
- ↑ Simeon Bennett, Novartis’ Afinitor gets OK of FDA, Bloomberg News (July 29, 2012). Retrieved 9/11/2012.
- ↑ Everolimus (Afinitor) patient drug information (Chemocare)
- ↑ Everolimus (Afinitor) patient drug information (UpToDate)
- Drugs
- Oral medications
- Protein expression-specific medications
- MTOR inhibitors
- TSC1 inhibitors
- TSC2 inhibitors
- B-cell acute lymphoblastic leukemia medications
- Breast cancer medications
- Diffuse large B-cell lymphoma medications
- Hodgkin lymphoma medications
- Mantle cell lymphoma medications
- Neuroendocrine tumor medications
- Pancreatic NET medications
- Peripheral T-cell lymphoma medications
- Renal cell carcinoma medications
- Thymoma medications
- Waldenström macroglobulinemia medications
- FDA approved in 2009
- PMDA approved drugs