Enasidenib is an isocitrate dehydrogenase-2 (IDH2) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) who harbor IDH2 mutations. As a targeted therapeutic agent, its efficacy is highly dependent on standardized medication use and close monitoring.

Precautions for Enasidenib Use

Prevention and Management of Differentiation Syndrome

Differentiation syndrome is the most serious potential risk during enasidenib treatment, with an incidence of 14% and potential life-threatening consequences.

Typical symptoms include fever, dyspnea, rapid weight gain, lymphadenopathy, or bone pain, which usually occur within 10 days to 5 months after starting medication.

Once this syndrome is suspected, initiate corticosteroid therapy (e.g., dexamethasone) immediately and continue hemodynamic monitoring until symptoms resolve.

If severe pulmonary symptoms or renal dysfunction persist for more than 48 hours, suspend medication. Resume treatment only after symptoms improve to grade 2 or below.

Risk of Embryo-Fetal Toxicity

Enasidenib may cause harm to the fetus.

Women of childbearing age must use highly effective contraceptive measures during treatment and for at least 1 month after the last dose.

Male patients with fertility plans should also use contraception during medication use and for 1 month after discontinuation.

Confirm the pregnancy status of female patients before treatment to avoid medication use during pregnancy.

Management of Gastrointestinal Adverse Reactions

Approximately 50% of patients may experience nausea, vomiting, or diarrhea, and 34% may have decreased appetite.

It is recommended to eat small, frequent meals, avoid high-fat foods, and use antiemetic drugs if necessary.

If a dose is missed due to vomiting, it can be taken as a supplement on the same day. Resume the normal medication schedule the next day; do not take a double dose to make up for the missed one.

Other Special Precautions

Non-infectious Leukocytosis: When the white blood cell count exceeds 30×10⁹/L, combined treatment with hydroxyurea is required. For patients unresponsive to hydroxyurea, suspend enasidenib.

Hyperbilirubinemia: 81% of patients may experience elevated bilirubin. If elevation persists for ≥2 weeks without evidence of liver injury, reduce the dose to 50mg per day.

Tumor Lysis Syndrome: Evaluate complete blood count and biochemical indicators before treatment, with particular attention to uric acid levels, and ensure adequate hydration.

Key Monitoring Points for Enasidenib Treatment

Safety Monitoring

Laboratory Tests: Monitor complete blood count, electrolytes (calcium, phosphorus, potassium), and liver function (bilirubin, transaminases) before treatment and every 2 weeks during the initial treatment phase for at least 3 months.

Differentiation Syndrome Screening: Pay special attention to symptoms related to respiration, renal function, and fluid retention; hospitalization for observation is necessary if needed.

Long-Term Follow-Up

Drug Interactions: Enasidenib may affect the activity of CYP enzymes and UGT1A1. Avoid concurrent use with hormonal contraceptives or other substrate drugs.

Impact on Fertility: Animal studies have shown that the drug may impair reproductive function. Discuss fertility preservation plans in advance.