Enasidenib (Idhifa) — Clinical FAQs

Question 1

What is Enasidenib FDA-approved to treat?

Accepted Answer

Enasidenib is FDA-approved for the following oncology indications: 1. Relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation as detected by an FDA-approved test — approved Aug 2017 (Study AG221-C-001).

Question 2

How does Enasidenib work (mechanism of action)?

Accepted Answer

Enasidenib is an allosteric inhibitor of mutant isocitrate dehydrogenase 2 (IDH2), including the most common IDH2 mutant isoforms R140Q and R172K. By inhibiting mutant IDH2, enasidenib blocks the neomorphic enzymatic activity that converts α-ketoglutarate to the oncometabolite 2-hydroxyglutarate (2-HG). Reduction of 2-HG relieves aberrant inhibition of histone and DNA demethylases (TET2, KDM), thereby restoring normal epigenetic regulation and promoting terminal myeloid differentiation of leukemic blasts rather than inducing apoptosis.

Question 3

How is Enasidenib administered?

Accepted Answer

Enasidenib is administered Oral (PO). Recommended dose: 100 mg PO once daily with or without food.

Question 4

What are the most common side effects of Enasidenib?

Accepted Answer

The most commonly reported side effects of Enasidenib (≥10% incidence) include: Nausea (~50%), Hyperbilirubinemia (~45%), Diarrhea (~43%), Vomiting (~34%), Decreased appetite and others (11 total). Consult your oncologist for complete prescribing information.

Question 5

Does Enasidenib have a black box warning?

Accepted Answer

Yes. Enasidenib carries FDA black box warning(s) regarding: 1. Differentiation syndrome: can be fatal if untreated. Signs/symptoms include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pericardial or pleural effusion, rapid weight gain, peripheral edema, rash, and renal dysfunction. If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours and hemodynamic monitoring; add hydroxyurea if WBC ≥30,000 cells/mm³; interrupt enasidenib only if signs/symptoms are severe and persist >48 hours despite corticosteroids

Question 6

Is Enasidenib safe during pregnancy?

Accepted Answer

Enasidenib pregnancy safety: Can cause embryo-fetal harm based on mechanism of action. Women of reproductive potential should use effective contraception during therapy and for ≥1 month after the last dose. Male patients with female partners of reproductive potential should use contraception for ≥1 month after the last dose. Breastfeeding should be discontinued.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

enasidenib — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms