Enasidenib is a targeted medication for isocitrate dehydrogenase-2 (IDH2) mutations, indicated for adult patients with relapsed or refractory acute myeloid leukemia (AML). As a prescription-only drug, close attention must be paid to its potential side effects and medication-related risks during clinical use.

What Are the Side Effects of Enasidenib?

Common Side Effects

Gastrointestinal reactions: Nausea (50%), vomiting (34%), diarrhea (43%).

Metabolic and nutritional abnormalities: Decreased appetite (34%).

Abnormal Laboratory Indicators

Elevated bilirubin (81%), of which 15% are severe abnormalities of Grade 3 or higher.

Decreased blood calcium (74%), decreased blood potassium (41%), and decreased blood phosphorus (27%).

Some patients may experience taste disorders (12%), non-infectious leukocytosis (12%), etc.

Severe Side Effects of Enasidenib

Differentiation Syndrome

Incidence and risk: Approximately 14% of patients develop differentiation syndrome after receiving enasidenib treatment. Symptoms may occur within 1 day to 5 months of medication initiation and can be life-threatening in severe cases.

Typical manifestations: Fever, dyspnea, hypoxemia, pleural effusion, peripheral edema (rapid weight gain), bone pain, and liver/kidney function impairment.

Management measures: Upon suspicion of differentiation syndrome, initiate corticosteroid therapy (e.g., dexamethasone) and hemodynamic monitoring immediately; hospitalization may be required if necessary.

Embryofetal Toxicity

Animal studies have shown that enasidenib can cause embryonic death or developmental abnormalities.

Contraception recommendations: Females and males of reproductive potential must use effective non-hormonal contraceptive methods during treatment and for 2 months after the last dose.

Other Severe Adverse Reactions

Tumor lysis syndrome: Risk assessment should be conducted in advance, and electrolytes and renal function should be monitored.

Non-infectious leukocytosis: When the white blood cell count is significantly elevated (> 30 × 10⁹/L), hydroxyurea should be used in combination; enasidenib may need to be discontinued if necessary.

Precautions for Enasidenib Administration

Pre-Medication Screening and Dosage Standards

Genetic testing: Only applicable to AML patients with confirmed IDH2 mutations via FDA-approved testing methods.

Recommended dosage: 100 mg orally once daily, with or without food; the tablet must be swallowed whole.

Dosage adjustment: Discontinue or reduce the dosage to 50 mg/day based on toxicity grading (see Table 1); permanent discontinuation is required in case of severe recurrence of toxicity.

Management of Drug Interactions

Enasidenib may affect the efficacy of co-administered drugs by inhibiting or inducing hepatic enzymes and transporters.

Avoid co-administration: Substrates of CYP1A2, CYP2C19, CYP3A, and OATP1B1/BCRP (e.g., certain antifungal drugs, hormonal contraceptives).

Monitoring requirements: When co-administered with P-glycoprotein substrates (e.g., digoxin), enhanced monitoring of adverse reactions is required.

Administration in Special Populations

Pregnant women: Contraindicated due to the risk of teratogenicity.

Lactating women: Breastfeeding is prohibited during treatment and for 2 months after drug discontinuation.

Elderly patients: No dosage adjustment is required, but close monitoring of liver/kidney function and hematological indicators is necessary.