Instructions for Enasidenib

1. Common names : Ensidipine, Enasidenib, Idhifa, Enasidenib mesylate

2. Indications:

Enasidenib (Enasidenib) is indicated for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with isocitrate dehydrogenase 2 (IDH2) mutations.

3. Usage and dosage:

1. Before medication: Doctors will choose to treat patients with ensidipine based on the presence of IDH2 mutations in the blood or bone marrow. Before initiating ensidipine, assess blood counts and blood chemistries for leukocytosis and tumor lysis syndrome and monitor at least every 2 weeks for at least the first 3 months of treatment. Handle any abnormal situations promptly.

2. Recommended dosage:

The recommended dose of ensidipine is 100 mg once daily, with or without food, until disease progression or unacceptable toxicity occurs. For patients without disease progression or unacceptable toxicity, treat for at least 6 months to allow time for clinical response.

4. Adverse reactions:

The most common adverse reactions (≥20%) of ensidipine include increased total bilirubin, decreased calcium, nausea, diarrhea, decreased potassium, vomiting, decreased appetite, and decreased phosphorus. The most common serious adverse reactions (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome;Severe differentiation syndrome events included pyrexia, acute renal failure, hypoxia, respiratory failure, and multiple organ failure.

5. Storage:

Ensidipine may be stored at 20°C-25°C (68°F-77°F); tolerances are allowed between15°C-30°C (59°F-86°F). Keep the bottle tightly closed. Store in original bottle (with desiccant tank) to prevent moisture.

6. Special groups:

1. Women: Based on animal embryo-fetal toxicity studies, when administered to pregnant women, ensidipineCan cause fetal damage, so women are advised not to breastfeed during drug treatment and for at least 2 months after the last dose; women of reproductive potential are advised to use effective contraception during drug treatment and for at least 2 months after the last dose.

2. Men: It is recommended that men with female partners of reproductive potential use effective contraception during treatment with ensidipine and for at least 2 months after the last dose of drug.

7. Mechanism of action:

Ensidipine is a small molecule inhibitor of isocitrate dehydrogenase2 (IDH2) enzyme. Etanacitinib targets mutant IDH2 variants R140Q, R172S, and R172K in vitro at approximately 40-fold lower concentrations than the wild-type enzyme. In a mouse xenograft model of IDH2-mutant acute myeloid leukemia, inhibition of the mutant IDH2 enzyme by enacinib resulted in reduced 2-hydroxyglutarate (2-HG) levels and induction of myeloid differentiation in vitro and in vivo. In blood samples from acute myeloid leukemia patients with mutated IDH2, ensidipine reduced 2-HG levels, reduced osteoblast counts, and increased the percentage of mature myeloid cells.