|Trade names||Synribo, Tekinex, others|
|Other names||Omacetaxine mepesuccinate, homoharringtonine (HHT)|
|Drug class||Protein synthesis inhibitor|
|Main uses||Chronic myeloid leukemia (CML)|
|Side effects||Low platelets, low red blood cells, low white blood cells, fever, diarrhea, nausea, pain|
|Subcutaneous, intravenous infusion|
|Typical dose||1.25 mg/m2|
|Metabolism||Mostly via plasma esterases|
|Elimination half-life||6 hours|
|Excretion||Urine (≤15% unchanged)|
|Chemical and physical data|
|Molar mass||545.629 g·mol−1|
|3D model (JSmol)|
Omacetaxine, sold under the brand name Synribo, is a medication used to treat chronic myeloid leukemia (CML). It is used in cases were other medications have not worked. It is given by injection under the skin.
Common side effects include low platelets, low red blood cells, low white blood cells, fever, diarrhea, nausea, and pain. Other side effects may include bleeding and infection. Use during pregnancy may harm the baby. It is a protein synthesis inhibitor.
Omacetaxine was approved for medical use in the United States in 2012. It is not approved in Europe. In the United States it costs about 1,200 USD for 3.5 mg as of 2021. It is made from a substance in the Chinese evergreen known as harringtonine.
The dose is 1.25 mg/m2.
It is initially given twice per day for 2 weeks followed by 2 weeks off.
In following rounds it is given for 1 week followed by 3 weeks off.
Common (1–10% 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.
Mechanism of action
Omacetaxine 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 acts only on the initial step of protein translation and does not inhibit protein synthesis from mRNAs that have already commenced translation.
HHT is a natural plant alkaloid derived from Cephalotaxus fortunei. HHT and related compound esters of cephalotaxine were described first in 1970, and were the subject of intensive research efforts by Chinese investigators to clarify their role as anticancer and antileukemic agents from the 1970s until the present.
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. 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.
Phase I studies including a small number of patients have shown benefit in treating myelodysplastic syndrome (MDS, 25 patients) and acute myelogenous leukaemia (AML, 76 patients). Patients with solid tumors did not benefit from omacetaxine.
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