Difference between revisions of "Midostaurin (Rydapt)"
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m (PeterYang moved page Midostaurin (PKC412) to Midostaurin (Rydapt): FDA approval) |
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| − | == | + | ==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>[[Media:Midostaurin.pdf | Midostaurin (Rydapt) package insert (locally hosted backup)]]</ref><ref>[http://rydapt.com/ Rydapt manufacturer's website]</ref> | |
| + | <br>Route: PO | ||
| + | <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 such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref> | ||
| + | |||
| + | ==Diseases for which it is used== | ||
| + | *[[Acute myeloid leukemia]] | ||
| + | *[[Systemic mastocytosis]] | ||
| + | |||
| + | ==Patient drug information== | ||
| + | *[https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/rydapt.pdf Midostaurin (Rydapt) package insert]<ref name="insert"></ref> | ||
==Preliminary data== | ==Preliminary data== | ||
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# Gotlib J, Berubé C, Growney JD, Chen CC, George TI, Williams C, Kajiguchi T, Ruan J, Lilleberg SL, Durocher JA, Lichy JH, Wang Y, Cohen PS, Arber DA, Heinrich MC, Neckers L, Galli SJ, Gilliland DG, Coutré SE. Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation. Blood. 2005 Oct 15;106(8):2865-70. Epub 2005 Jun 21. [http://www.bloodjournal.org/content/106/8/2865.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15972446 PubMed] | # Gotlib J, Berubé C, Growney JD, Chen CC, George TI, Williams C, Kajiguchi T, Ruan J, Lilleberg SL, Durocher JA, Lichy JH, Wang Y, Cohen PS, Arber DA, Heinrich MC, Neckers L, Galli SJ, Gilliland DG, Coutré SE. Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation. Blood. 2005 Oct 15;106(8):2865-70. Epub 2005 Jun 21. [http://www.bloodjournal.org/content/106/8/2865.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15972446 PubMed] | ||
# Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. [http://www.nejm.org/doi/full/10.1056/NEJMoa1513098 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27355533 PubMed] | # Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. [http://www.nejm.org/doi/full/10.1056/NEJMoa1513098 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27355533 PubMed] | ||
| + | |||
| + | ==History of changes in FDA indication== | ||
| + | *4/28/2017: [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 FLT3 mutation-positive (FLT3+), as detected by an FDA-approved test, in combination with standard [[Cytarabine (Cytosar)|cytarabine]] and [[Daunorubicin (Cerubidine)|daunorubicin]] induction and cytarabine consolidation." | ||
| + | *4/28/2017: [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." | ||
| + | |||
| + | ==Also known as== | ||
| + | PKC412 | ||
| + | |||
| + | ==References== | ||
| + | <references/> | ||
[[Category:Drug index]] | [[Category:Drug index]] | ||
| Line 27: | Line 48: | ||
[[Category:Myelodysplastic syndrome medications]] | [[Category:Myelodysplastic syndrome medications]] | ||
[[Category:Systemic mastocytosis medications]] | [[Category:Systemic mastocytosis medications]] | ||
| − | [[Category: | + | [[Category:Drugs FDA approved in 2017]] |
Revision as of 23:56, 29 April 2017
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 such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]
Diseases for which it is used
Patient drug information
Preliminary data
Acute myeloid leukemia
- Stone RM, DeAngelo DJ, Klimek V, Galinsky I, Estey E, Nimer SD, Grandin W, Lebwohl D, Wang Y, Cohen P, Fox EA, Neuberg D, Clark J, Gilliland DG, Griffin JD. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood. 2005 Jan 1;105(1):54-60. Epub 2004 Sep 2. link to original article PubMed
- Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, Fox E, Ehninger G, Feldman EJ, Schiller GJ, Klimek VM, Nimer SD, Gilliland DG, Dutreix C, Huntsman-Labed A, Virkus J, Giles FJ. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010 Oct 1;28(28):4339-45. Epub 2010 Aug 23. link to original article PubMed
Myelodysplastic syndrome
- Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, Fox E, Ehninger G, Feldman EJ, Schiller GJ, Klimek VM, Nimer SD, Gilliland DG, Dutreix C, Huntsman-Labed A, Virkus J, Giles FJ. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010 Oct 1;28(28):4339-45. Epub 2010 Aug 23. link to original article PubMed
Systemic mastocytosis
- Gotlib J, Berubé C, Growney JD, Chen CC, George TI, Williams C, Kajiguchi T, Ruan J, Lilleberg SL, Durocher JA, Lichy JH, Wang Y, Cohen PS, Arber DA, Heinrich MC, Neckers L, Galli SJ, Gilliland DG, Coutré SE. Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation. Blood. 2005 Oct 15;106(8):2865-70. Epub 2005 Jun 21. link to original article PubMed
- Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. link to original article PubMed
History of changes in FDA indication
- 4/28/2017: 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."
- 4/28/2017: FDA approved "for the treatment of adults with aggressive systemic mastocytosis (SM), SM with associated hematological neoplasm, or mast cell leukemia."
Also known as
PKC412