Difference between revisions of "Omacetaxine (Synribo)"

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m (PeterYang moved page Omacetaxine mepesuccinate (Omapro) to Omacetaxine mepesuccinate (Synribo): Omacetaxine mepesuccinate (Synribo) FDA approval)
(FDA approval)
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'''In clinical trials'''.  May also be known as homoharringtonine (HHT).
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'''FDA approved 10/26/2012'''.  Also known as HHT, homoharringtonine, or Omapro.
  
 
==General information==
 
==General information==
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Class/mechanism: Semisynthetic form of homoharringtonine (HHT), which is a natural alkaloid that inhibits protein synthesis (such as human induced myeloid leukemia cell differentiation protein MCL1), promotes apoptosis, and is being investigated for its activity in imatinib-resistant chronic myeloid leukemia (CML) patients with the T315I mutation.<ref>Quintás-Cardama A, Kantarjian H, Cortes J. Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009. Cancer. 2009 Dec 1;115(23):5382-93. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.24601/full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19739234 PubMed]</ref>
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Class/mechanism: Cephalotaxine ester & natural alkaloid that inhibits protein synthesis/translation/elongation; prepared via a semi-synthetic process from cephalotaxine, an extract of Cephalotaxus species leaves.  Mechanism is not fully understood, but omacetaxine mepesuccinate inhibits protein synthesis and promotes apoptosis in a manner that does not involve direct binding of Bcr-Abl.  Omacetaxine mepesuccinate has been observed to bind to the A-site cleft in the large ribosomal subunit of a type of archaeabacteria.  It reduces levels of Bcr-Abl and human induced myeloid leukemia cell differentiation protein Mcl-1, an anti-apoptotic Bcl-2 family member.  Omacetaxine mepesuccinate has been seen to have activity in mouse models with wild-type Bcr-Abl, as well as imatinib-resistant chronic myeloid leukemia (CML) models with the T315I mutation.<ref name="insert">[http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203585lbl.pdf Omacetaxine mepesuccinate (Synribo) package insert]</ref><ref>[[Media:Omacetaxine.pdf | Omacetaxine mepesuccinate (Synribo) package insert (locally hosted backup)]]</ref><ref>Quintás-Cardama A, Kantarjian H, Cortes J. Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009. Cancer. 2009 Dec 1;115(23):5382-93. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.24601/full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19739234 PubMed]</ref>
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<br>Route: IV, SC
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Route: IV, SC
 
<br>Extravasation: no information
 
<br>Extravasation: no information
  
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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 package insert.
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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>
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==Diseases for which it is used==
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*[[Chronic myelogenous leukemia]]
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==Clinical trials==
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*[http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=114&abstractID=100567 Subcutaneous omacetaxine mepesuccinate in patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) resistant/intolerant to two or three approved tyrosine-kinase inhibitors (TKIs)] (2012 ASCO Annual Meeting Abstract 6513)
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*[http://clinicaltrials.gov/ct2/show/NCT01272245 Omacetaxine and Low Dose Cytarabine in Older Patients With Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS)]
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*[http://clinicaltrials.gov/ct2/show/NCT00675350 Pharmacokinetic (PK) Study of Homoharringtonine (Omacetaxine Mepesuccinate) Administered Subcutaneously to Patients With Advanced Solid and Hematologic Tumors]
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*[http://clinicaltrials.gov/ct2/show/NCT00462943 Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML]
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*[http://clinicaltrials.gov/ct2/show/NCT00375219 Homoharringtonine (Omacetaxine Mepesuccinate) in Treating Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL Gene Mutation]<ref>Cortes J, Lipton JH, Rea D, Digumarti R, Chuah C, Nanda N, Benichou AC, Craig AR, Michallet M, Nicolini FE, Kantarjian H; on behalf of the Omacetaxine 202 Study Group. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 2012 Sep 27;120(13):2573-2580. Epub 2012 Aug 15. [http://bloodjournal.hematologylibrary.org/content/120/13/2573.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22896000 PubMed]</ref>
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*[http://clinicaltrials.gov/ct2/show/NCT00114959 Homoharringtonine With Oral Gleevec in Chronic, Accelerated and Blast Phase Chronic Myeloid Leukemia (CML)]
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*[http://clinicaltrials.gov/ct2/show/NCT00003239 Chemotherapy and Biological Therapy in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia]
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*[http://clinicaltrials.gov/ct2/show/NCT00006364 Homoharringtonine in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia]
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*[http://clinicaltrials.gov/ct2/show/NCT00002574 Homoharringtonine and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia]
  
 
==Patient drug information==
 
==Patient drug information==
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No information available.
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*Brief patient counseling information can be found on [http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203585lbl.pdf#page=10 page 10 of the Omacetaxine mepesuccinate (Synribo) package insert]<ref name="insert"></ref>
  
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==History of changes in FDA indication==
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*10/26/2012: FDA approved for "treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKI)."<ref name="insert"></ref>
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==References==
 
==References==
 
<references/>
 
<references/>
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[[Category:Drug index]]
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[[Category:Chemotherapy]]
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[[Category:Bcr-Abl inhibitors]]
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[[Category:Cephalotaxine]]
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[[Category:Chronic myelogenous leukemia medications]]

Revision as of 22:54, 26 October 2012

FDA approved 10/26/2012. Also known as HHT, homoharringtonine, or Omapro.

General information

Class/mechanism: Cephalotaxine ester & natural alkaloid that inhibits protein synthesis/translation/elongation; prepared via a semi-synthetic process from cephalotaxine, an extract of Cephalotaxus species leaves. Mechanism is not fully understood, but omacetaxine mepesuccinate inhibits protein synthesis and promotes apoptosis in a manner that does not involve direct binding of Bcr-Abl. Omacetaxine mepesuccinate has been observed to bind to the A-site cleft in the large ribosomal subunit of a type of archaeabacteria. It reduces levels of Bcr-Abl and human induced myeloid leukemia cell differentiation protein Mcl-1, an anti-apoptotic Bcl-2 family member. Omacetaxine mepesuccinate has been seen to have activity in mouse models with wild-type Bcr-Abl, as well as imatinib-resistant chronic myeloid leukemia (CML) models with the T315I mutation.[1][2][3]

Route: IV, SC
Extravasation: no information

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

Clinical trials

Patient drug information

History of changes in FDA indication

  • 10/26/2012: FDA approved for "treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKI)."[1]

References

  1. ↑ 1.0 1.1 1.2 1.3 Omacetaxine mepesuccinate (Synribo) package insert
  2. ↑ Omacetaxine mepesuccinate (Synribo) package insert (locally hosted backup)
  3. ↑ Quintás-Cardama A, Kantarjian H, Cortes J. Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009. Cancer. 2009 Dec 1;115(23):5382-93. link to original article PubMed
  4. ↑ Cortes J, Lipton JH, Rea D, Digumarti R, Chuah C, Nanda N, Benichou AC, Craig AR, Michallet M, Nicolini FE, Kantarjian H; on behalf of the Omacetaxine 202 Study Group. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 2012 Sep 27;120(13):2573-2580. Epub 2012 Aug 15. link to original article contains verified protocol PubMed
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