|Other names||Enasidenib mesylate, AG-221|
|Drug class||Isocitrate dehydrogenase 2 inhibitor|
|Main uses||Acute myeloid leukemia (AML)|
|Side effects||Nausea, diarrhea, high bilirubin, lose of appetite|
|Typical dose||100mg OD|
|Chemical and physical data|
|Molar mass||473.383 g·mol−1|
|3D model (JSmol)|
Enasidenib, sold under the brand name Idhifa, is a medication used to treat acute myeloid leukemia (AML) with mutations of the isocitrate dehydrogenase 2 (IDH2) gene. It is used when other treatments have failed. It is taken by mouth.
Common side effects include nausea, diarrhea, high bilirubin, and lose of appetite. Other side effects may include differentiation syndrome, tumor lysis syndrome, lung problems, infertility, and kidney problems. Use during pregnancy may harm the baby. It works by blocking the action of mutated IDH2.
Enasidenib was approved for medical use in the United States in 2017. It was denied approval in Europe in 2019 due to insufficient evidence of benefit. In the United States a month of treatment costs about 29,500 USD as of 2021.
It is taken at a dose of 100 mg per day.
Isocitrate dehydrogenase is a critical enzyme in the citric acid cycle. Mutated forms of IDH produce high levels of the (R)-enantiomer of 2-hydroxyglutarate (R-2-HG) and can contribute to the growth of tumors. IDH1 catalyzes this reaction in the cytoplasm, while IDH2 catalyzes this reaction in mitochondria. Mutations of IDH2 are more common than IDH1 mutations, 8 to 19% compared to 7 to 14% respectively, in those affected with AML. Enasidenib disrupts this cycle by decreasing total (R)-2-HG levels in the mitochondria.[medical citation needed]
Enasidenib was approved by the FDA in August 2017, for relapsed or refractory acute myeloid leukemia (AML) in people with specific mutations of the IDH2 gene, determined by an FDA-approved IDH2 companion diagnostic test. The FDA considers it to be a first-in-class medication.
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