omacetaxine mepesuccinate

Omacetaxine/homoharringtonine [https://web.archive.org/web/20250125171150/https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm?panel=0&drugname=Omacetaxine was] indicated for use as a treatment for patients with chronic myeloid leukaemia who are resistant or intolerant of tyrosine kinase inhibitors.{{cite web|title=SYNRIBO (omacetaxine mepesuccinate) injection, powder, lyophilized, for solution [Cephalon, Inc.]|work=DailyMed|publisher=Cephalon, Inc.|date=October 2012|access-date=18 February 2014|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=83a504ef-cf92-467d-9ecf-d251194a3484}}{{cite book|title=Martindale: The Complete Drug Reference|series=Medicines Complete|publisher=Pharmaceutical Press|date=14 November 2012|chapter=Omacetaxine Mepesuccinate|editor=Sweetman, S}}{{cite book|last1=Lacroix|first1=Marc|name-list-style=vanc|title=Targeted Therapies in Cancer|date=2014|publisher=Nova Sciences Publishers|location=Hauppauge , NY|isbn=978-1-63321-687-7|url=https://www.novapublishers.com/catalog/product_info.php?products_id=50994|access-date=2014-07-13|archive-url=https://web.archive.org/web/20150626172243/https://www.novapublishers.com/catalog/product_info.php?products_id=50994|archive-date=2015-06-26|url-status=dead}}

In June 2009, results of a long-term open label Phase II study were published, which investigated the use of omacetaxine infusions in CML patients. After twelve months of treatment, about one third of patients showed a cytogenetic response.{{cite journal | vauthors = Li YF, Deng ZK, Xuan HB, Zhu JB, Ding BH, Liu XN, Chen BA | title = Prolonged chronic phase in chronic myelogenous leukemia after homoharringtonine therapy | journal = Chinese Medical Journal | volume = 122 | issue = 12 | pages = 1413–7 | date = June 2009 | pmid = 19567163 }} A study in patients who had failed imatinib and who had the drug resistant T315I mutation achieved cytogenetic response in 28% of patients and hematologic response in 80% of patients, according to preliminary data.{{cite journal | vauthors = Quintás-Cardama A, Kantarjian H, Cortes J | title = Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009 | journal = Cancer | volume = 115 | issue = 23 | pages = 5382–93 | date = December 2009 | pmid = 19739234 | doi = 10.1002/cncr.24601 | doi-access = free }}

Phase I studies including a small number of patients have shown benefit in treating myelodysplastic syndrome (MDS, 25 patients){{cite journal | vauthors = Wu L, Li X, Su J, Chang C, He Q, Zhang X, Xu L, Song L, Pu Q | display-authors = 6 | title = Effect of low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor priming regimen on patients with advanced myelodysplastic syndrome or acute myeloid leukemia transformed from myelodysplastic syndrome | journal = Leukemia & Lymphoma | volume = 50 | issue = 9 | pages = 1461–7 | date = September 2009 | pmid = 19672772 | doi = 10.1080/10428190903096719 | s2cid = 10675425 }} and acute myelogenous leukaemia (AML, 76 patients).{{cite journal | vauthors = Gu LF, Zhang WG, Wang FX, Cao XM, Chen YX, He AL, Liu J, Ma XR | display-authors = 6 | title = Low dose of homoharringtonine and cytarabine combined with granulocyte colony-stimulating factor priming on the outcome of relapsed or refractory acute myeloid leukemia | journal = Journal of Cancer Research and Clinical Oncology | volume = 137 | issue = 6 | pages = 997–1003 | date = June 2011 | pmid = 21152934 | doi = 10.1007/s00432-010-0947-z | s2cid = 20406046 }} Patients with solid tumors did not benefit from omacetaxine.{{cite journal | vauthors = Kantarjian HM, Talpaz M, Santini V, Murgo A, Cheson B, O'Brien SM | title = Homoharringtonine: history, current research, and future direction | journal = Cancer | volume = 92 | issue = 6 | pages = 1591–605 | date = September 2001 | pmid = 11745238 | doi = 10.1002/1097-0142(20010915)92:6<1591::AID-CNCR1485>3.0.CO;2-U | s2cid = 221577386 }}

By frequency:

Very common (>10% frequency):

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• Diarrhea
• Myelosuppression^†
• Injection site reactions
• Nausea
• Fatigue
• Fever
• Muscle weakness
• Joint pain
• Headache
• Cough
• Hair loss
• Constipation
• Nosebleeds
• Upper abdominal pain
• Pain in the extremities
• Oedema
• Vomiting
• Back pain
• Hyperglycemia, sometimes extreme
• Gout
• Rash
• Insomnia

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Common (1–10% frequency):

• Seizures
• Haemorrhage

^† Myelosuppression, including: thrombocytopenia, anaemia, neutropenia and lymphopenia, in descending order of frequency.

Omacetaxine mepesuccinate can cause fetal harm when administered to a pregnant woman. Women using HHT should avoid becoming pregnant and also avoid nursing while receiving HHT.{{Cite web | title = SYNRIBOTM (omacetaxine mepesuccinate) drug label |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203585lbl.pdf |work = FDA}}

Omacetaxine mepesuccinate is a protein translation inhibitor. It inhibits protein translation by preventing the initial elongation step of protein synthesis. It interacts with the ribosomal A-site and prevents the correct positioning of amino acid side chains of incoming aminoacyl-tRNAs. Omacetaxine mepesuccinate acts only on the initial step of protein translation and does not inhibit protein synthesis from mRNAs that have already commenced translation.{{cite journal | vauthors = Wetzler M, Segal D | title = Omacetaxine as an anticancer therapeutic: what is old is new again | journal = Current Pharmaceutical Design | volume = 17 | issue = 1 | pages = 59–64 | date = 2011 | pmid = 21294709 | doi = 10.2174/138161211795049778 }}

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{{Intracellular chemotherapeutic agents}}

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