Difference between revisions of "Midostaurin (Rydapt)"
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==General information== | ==General information== | ||
| − | Class/mechanism: FLT3 inhibitor, tyrosine kinase inhibitor (TKI). Midostaurin or its active metabolites CGP62221 and CGP52421 inhibit activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFRα/β, VEGFR2, and members of the serine/threonine kinase PKC (protein kinase C) family. Midostaurin induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. Midostaurin also causes apoptosis in mast cells and inhibits histamine release, proliferation, and KIT signaling.<ref name=insert>[https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/rydapt.pdf Midostaurin (Rydapt) package insert]</ref><ref>[[ | + | Class/mechanism: FLT3 inhibitor, tyrosine kinase inhibitor (TKI). Midostaurin or its active metabolites CGP62221 and CGP52421 inhibit activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFRα/β, VEGFR2, and members of the serine/threonine kinase PKC (protein kinase C) family. Midostaurin induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. Midostaurin also causes apoptosis in mast cells and inhibits histamine release, proliferation, and KIT signaling.<ref name=insert>[https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/rydapt.pdf Midostaurin (Rydapt) package insert]</ref><ref>[[:File:Midostaurin.pdf | Midostaurin (Rydapt) package insert (locally hosted backup)]]</ref><ref>[http://rydapt.com/ Rydapt manufacturer's website]</ref> |
<br>Route: PO | <br>Route: PO | ||
<br>Extravasation: n/a | <br>Extravasation: n/a | ||
| − | 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 | + | 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 or the prescribing information.<ref name="insert"></ref> |
==Diseases for which it is used== | ==Diseases for which it is used== | ||
| Line 15: | Line 15: | ||
==History of changes in FDA indication== | ==History of changes in FDA indication== | ||
| − | * | + | *2017-04-28: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm555756.htm FDA approved] for the treatment of adult patients with newly diagnosed [[Acute myeloid leukemia|acute myeloid leukemia (AML)]] who are [[Biomarkers#FLT3|FLT3]] [[Biomarkers#Alterations|mutation-positive]] (FLT3+), as detected by an FDA-approved test, in combination with standard [[Cytarabine (Ara-C)|cytarabine]] and [[Daunorubicin (Cerubidine)|daunorubicin]] induction and cytarabine consolidation. ''(Based on RATIFY)'' |
| − | * | + | *2017-04-28: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm555756.htm FDA approved] for the treatment of adults with [[Systemic mastocytosis|aggressive systemic mastocytosis (SM)]], SM with associated hematological neoplasm, or mast cell leukemia. ''(Based on CPKC412D2201 and CEREMAST)'' |
| + | ==History of changes in EMA indication== | ||
| + | *2017-09-18: Initial authorization in combination with standard daunorubicin and cytarabine induction and high dose cytarabine consolidation chemotherapy, and for patients in complete response followed by Rydapt single agent maintenance therapy, for adult patients with newly diagnosed [[acute myeloid leukemia|acute myeloid leukaemia (AML)]] who are FLT3 mutation positive. | ||
| + | *2017-09-18: Initial authorization as monotherapy for the treatment of adult patients with [[systemic mastocytosis|aggressive systemic mastocytosis (ASM)]], systemic mastocytosis with associated haematological neoplasm (SM AHN), or mast cell leukaemia (MCL). | ||
==Other information== | ==Other information== | ||
| − | # Heidel F, Solem FK, Breitenbuecher F, Lipka DB, Kasper S, Thiede MH, Brandts C, Serve H, Roesel J, Giles F, Feldman E, Ehninger G, Schiller GJ, Nimer S, Stone RM, Wang Y, Kindler T, Cohen PS, Huber C, Fischer T. Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain. Blood. 2006 Jan 1;107(1):293-300. Epub 2005 Sep 8. [ | + | # Heidel F, Solem FK, Breitenbuecher F, Lipka DB, Kasper S, Thiede MH, Brandts C, Serve H, Roesel J, Giles F, Feldman E, Ehninger G, Schiller GJ, Nimer S, Stone RM, Wang Y, Kindler T, Cohen PS, Huber C, Fischer T. Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain. Blood. 2006 Jan 1;107(1):293-300. Epub 2005 Sep 8. [https://doi.org/10.1182/blood-2005-06-2469 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16150941/ PubMed] |
==Also known as== | ==Also known as== | ||
| − | *'''Code name:''' | + | *'''Code name:''' PKC-412 |
| − | *'''Brand | + | *'''Brand names:''' Rydapt, Tauritmo |
==References== | ==References== | ||
| Line 32: | Line 35: | ||
[[Category:Mutation-specific medications]] | [[Category:Mutation-specific medications]] | ||
| − | |||
[[Category:FLT3 inhibitors]] | [[Category:FLT3 inhibitors]] | ||
[[Category:KIT inhibitors]] | [[Category:KIT inhibitors]] | ||
| Line 41: | Line 43: | ||
[[Category:Systemic mastocytosis medications]] | [[Category:Systemic mastocytosis medications]] | ||
| − | [[Category:EMA approved | + | [[Category:EMA approved in 2017]] |
| − | |||
[[Category:FDA approved in 2017]] | [[Category:FDA approved in 2017]] | ||
Latest revision as of 01:02, 29 June 2024
General information
Class/mechanism: FLT3 inhibitor, tyrosine kinase inhibitor (TKI). Midostaurin or its active metabolites CGP62221 and CGP52421 inhibit activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFRα/β, VEGFR2, and members of the serine/threonine kinase PKC (protein kinase C) family. Midostaurin induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. Midostaurin also causes apoptosis in mast cells and inhibits histamine release, proliferation, and KIT signaling.[1][2][3]
Route: PO
Extravasation: n/a
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 or the prescribing information.[1]
Diseases for which it is used
Patient drug information
History of changes in FDA indication
- 2017-04-28: FDA approved for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive (FLT3+), as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation. (Based on RATIFY)
- 2017-04-28: FDA approved for the treatment of adults with aggressive systemic mastocytosis (SM), SM with associated hematological neoplasm, or mast cell leukemia. (Based on CPKC412D2201 and CEREMAST)
History of changes in EMA indication
- 2017-09-18: Initial authorization in combination with standard daunorubicin and cytarabine induction and high dose cytarabine consolidation chemotherapy, and for patients in complete response followed by Rydapt single agent maintenance therapy, for adult patients with newly diagnosed acute myeloid leukaemia (AML) who are FLT3 mutation positive.
- 2017-09-18: Initial authorization as monotherapy for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated haematological neoplasm (SM AHN), or mast cell leukaemia (MCL).
Other information
- Heidel F, Solem FK, Breitenbuecher F, Lipka DB, Kasper S, Thiede MH, Brandts C, Serve H, Roesel J, Giles F, Feldman E, Ehninger G, Schiller GJ, Nimer S, Stone RM, Wang Y, Kindler T, Cohen PS, Huber C, Fischer T. Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain. Blood. 2006 Jan 1;107(1):293-300. Epub 2005 Sep 8. link to original article PubMed
Also known as
- Code name: PKC-412
- Brand names: Rydapt, Tauritmo