Enasidenib

Indications

Enasidenib is used for: Acute Myeloid Leukemia

Adult Dose

Acute Myeloid Leukemia Indicated for relapsed/refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test 100 mg PO qDay with or without food until disease progression or unacceptable toxicity

Child Dose

Renal Dose

Administration

Take once at the same time each day; may be taken with or without food

Contra Indications

Precautions

Differentiation syndrome reported, which can be fatal if not treated Based on animal embryofetal toxicity studies, can cause embryofetal harm when administered to pregnant women

Pregnancy-Lactation

Pregnancy Based on animal embryofetal toxicity studies, can cause fetal harm when administered to pregnant women There are no available data on use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage Contraception Females Females of reproductive potential should avoid becoming pregnant while receiving enasidenib Advise women to use effective contraception during treatment with enasidenib and for at least 1 month after the last dose Coadministration of enasidenib may increase or decrease the concentrations of combined hormonal contraceptives; the clinical significance of this potential drug interaction is unknown at this time Males Advise males with female partners of reproductive potential to use effective contraception during treatment with enasidenib and for at least 1 month after the last dose Lactation There are no data on the presence of enasidenib or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants, advise women not to breastfeed during treatment with enasidenib and for at least 1 month after the last dose

Interactions

Adverse Effects

Side effects of Enasidenib : >10% Total bilirubin increased, all grades (81%) Calcium decreased, all grades (74%) Nausea, all grades (50%) Diarrhea, all grades (43%) Potassium decreased, all grades (41%) Vomiting, all grades (34%) Decreased appetite, all grades (34%) Phosphorus decreased, all grades (27%) Total bilirubin increased, grade ≥3 (15%) Potassium decreased, grade ≥3 (15%) Differentiation syndrome, all grades (14%) Noninfectious leukocytosis, all grades (12%) Dysgeusia, all grades (12%) 1-10% Pulmonary edema (≤10%) Acute respiratory distress syndrome (≤10%) Diarrhea, grade ≥3 (8%) Calcium decreased, grade ≥3 (8%) Phosphorus decreased, grade ≥3 (8%) Differentiation syndrome, grade ≥3 (7%) Noninfectious leukocytosis, grade ≥3 (6%) Tumor lysis syndrome, grade ≥3 (6%) Nausea, grade ≥3 (5%) Vomiting, grade ≥3 (4%) Decreased appetite, grade ≥3 (4%)

Mechanism of Action

Oral, reversible, selective isocitrate dehydrogenase-2 enzyme (IDH2) inhibitor; inhibits mutant IDH2 enzyme, which decreases 2-hydroxyglutarate (2-HG) levels and induces myeloid differentiation in vitro Enasidenib may have clinical activity in IDH2-mutant AML through the reduction of 2-HG levels and the induction of blast differentiation