Idhifa

Acute myeloid leukemia (AML) — relapsed or refractory, with an IDH2 mutation as detected by an FDA-approved test

100 mg orally once daily until disease progression or unacceptable toxicity
Take with or without food
Minimum 6 months of treatment to allow time for clinical response

Tablets: 50 mg, 100 mg

None listed.

• Differentiation Syndrome: 14% (7% Grade ≥3), including fatal cases. Symptoms: dyspnea, pulmonary infiltrates, pleural/pericardial effusions, weight gain, fever, hypotension. Treat with corticosteroids. Withhold if not responsive within 48 hours.
• Elevated Bilirubin: 81% (15% Grade ≥3). Primarily indirect/unconjugated bilirubin due to inhibition of UGT1A1. Reduced as 2-HG levels normalize. Monitor LFTs.
• Tumor Lysis Syndrome: Monitor patients at risk.
• Embryo-Fetal Toxicity

Nausea (50%), total bilirubin increase (81%), indirect bilirubin increase (67%), diarrhea (43%), decreased appetite (34%), vomiting (34%), fatigue (28%), differentiation syndrome (14%), decreased calcium (24%), decreased potassium (17%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Enasidenib is a small-molecule inhibitor of mutant isocitrate dehydrogenase 2 (IDH2) enzyme. Susceptible IDH2 mutations (R140Q, R172K, R172S, R172G) produce the oncometabolite D-2-hydroxyglutarate (2-HG) at elevated levels, causing epigenetic dysregulation and a block in cellular differentiation. Enasidenib inhibits the mutant IDH2 enzyme, reducing 2-HG levels and restoring myeloid differentiation in AML blasts.

Tmax: 4 hours. Half-life: approximately 137 hours (terminal). Protein binding: 98.5%. Metabolized primarily by CYP enzymes (multiple). Fecal excretion (89%), urinary excretion (11%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• AG-221-C-001 — Enasidenib in IDH2-mutated relapsed/refractory AML. Phase I/II, n=239.
  🔬 NCT01915498 ↗ 📄 Primary Publication ↗

Idhifa has FDA-approved indications across the following cancer types covered on PipelineEvidence: