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 an IDH2 mutation. As a targeted therapeutic agent, its efficacy highly depends on standardized administration and close monitoring.

Precautions for Enasidenib Administration

Prevention and Management of Differentiation Syndrome

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

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

Once this syndrome is suspected, glucocorticoid therapy (e.g., dexamethasone) must be initiated immediately, along with continuous hemodynamic monitoring, until symptoms resolve.

If severe pulmonary symptoms or renal dysfunction occur for more than 48 hours, medication administration should be suspended. Treatment can be resumed only after symptoms improve to grade 2 or lower.

Risk of Embryofetal Toxicity

Enasidenib may cause harm to the fetus.

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

Male patients who plan to have children should also use contraception during medication administration and for 1 month after discontinuing the drug.

The pregnancy status of female patients must be confirmed 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% of patients 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, the missed dose can be taken on the same day; resume the normal dosing schedule the next day, and 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, combination therapy with hydroxyurea is required. If hydroxyurea is ineffective, enasidenib administration should be suspended.

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

Tumor Lysis Syndrome: Before treatment, blood routine and biochemical indicators (with particular attention to uric acid levels) should be evaluated, and adequate hydration must be ensured.

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 phase of treatment, 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. Concurrent use with hormonal contraceptives or other substrate drugs should be avoided.

Impact on Fertility: Animal studies have shown that the drug may impair reproductive function; it is necessary to discuss fertility preservation plans in advance.