Enasidenib is indicated for adult patients with relapsed or refractory acute myeloid leukemia (AML) who have been diagnosed with an isocitrate dehydrogenase-2 (IDH2) mutation using an FDA-approved test.
Enasidenib Indications
Adult patients with relapsed or refractory acute myeloid leukemia (AML) and confirmed IDH2 mutation using an FDA-approved test.
Indications
Adult patients with IDH2 mutation who are previously treated but whose disease has relapsed or is ineffective.
Orphan Drug Designation: The U.S. Food and Drug Administration (FDA) has granted enasidenib orphan drug designation for this use.
The presence of an IDH2 mutation must be confirmed by an FDA-approved diagnostic test before initiating treatment.
Enasidenib Dosage Guidelines
1. Pre-treatment Screening
(1) Confirm the presence of IDH2 mutation in peripheral blood or bone marrow before initiating treatment;
(2) Assess complete blood count (CBC) and blood chemistry to rule out leukocytosis and tumor lysis syndrome.
(3) Confirm pregnancy status in women of childbearing potential.
2. Patient Monitoring
(1) Monitor CBC and blood chemistry at least every 2 weeks for at least 3 months during the initial treatment period.
(2) Monitor for signs and symptoms of differentiation syndrome, such as fever, dyspnea, acute respiratory distress, pulmonary infiltration, pleural or pericardial effusion, rapid weight gain, peripheral edema, lymphadenopathy, bone pain, and liver, kidney, or multiple organ dysfunction.
3. Administration
Administer orally once daily at approximately the same time each day, regardless of meal times; swallow whole with water, do not chew, crush, or break.
4. Management of Vomiting and Missed Doses
If vomiting, a missed dose, or a dose not taken at the usual time occurs, take the missed dose as soon as possible on the same day, and resume the normal dosage the following day. Do not take a double dose to make up for a missed dose.
5. Dosage
Adult AML patients take 100 mg orally once daily until disease progression or unacceptable toxicity occurs.
6. Continuation of Treatment
Most patients achieve optimal response within 6 months of starting entasidenib treatment; therefore, treatment should be continued for at least 6 months to ensure efficacy.
Enasidenib Dosage Adjustment
1. Differentiation Syndrome
If severe pulmonary symptoms requiring respiratory support (e.g., intubation, assisted ventilation) and/or persistent renal dysfunction after more than 48 hours of systemic corticosteroid treatment occur, entasidenib should be discontinued until toxicity improves to grade 2 or below.
2. Leukocytosis
If leukocytosis persists after hydroxyurea treatment, entasidenib should be discontinued.
3. Hepatotoxicity
If serum bilirubin concentration is >3 times the upper limit of normal (ULN) and persists for ≥2 weeks (without elevated ALT/AST or other liver disease), reduce the dose to 50 mg once daily.
When serum bilirubin improves to <2 times the ULN, increase the dose back to 100 mg once daily.
4. Tumor lysis syndrome
If grade 3 or higher tumor lysis syndrome occurs, discontinue emsidipin.
If improvement to grade 2 or below, resume dosing at 50 mg once daily. If improvement to grade 1 or below, the dose can be increased back to 100 mg once daily. If relapse occurs, discontinue the drug permanently.
5. Other toxicities
If grade 3 or higher adverse reactions occur, discontinue emsidipin. If improvement to grade 2 or below, resume dosing at 50 mg once daily. If improvement to grade 1 or below, the dose can be increased back to 100 mg once daily. If relapse occurs, discontinue the drug permanently.
Enasidenib Dosage Adjustment in Special Populations
1. Mild hepatic impairment (total bilirubin ≤ ULN with AST > ULN, or total bilirubin 1–1.5 times ULN with any AST level): No dose adjustment required.
2. Glomerular filtration rate (eGFR) ≥ 30 mL/min: No dose adjustment required.
3. Elderly patients: No dose adjustment required.
