enasidinib (en-a-sid-a-nib) Idhifa

 Indications

Relapsed or refractory acute myeloid leukemia

(AML) with an isocitrate dehydrogenase-2 (IDH2) mutation.

Action

Inhibits the IDH2 enzyme, especially the mutant variants,

R140Q, R172S. and R172K. Inhibiting these mutant

enzymes results in decreased 2-hydroxyglutarate

levels with subsequent induction of myeloid differentiation.

Overall effect in patients with AML is a reduction in

blast cells and an increased proportion of mature myeloid

cells. Therapeutic Effects: Promotion of complete

remission and reduction in need for transfusions.

Pharmacokinetics

Absorption: 57% absorbed following oral administration.

Distribution: 55.8 L.

Protein Binding: 98.5%.

Metabolism and Excretion: Metabolized by numerous

CYP450 isoenzymes (CYP1A2, CYP2B6,

CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) to

an active metabolite (AGI-16903). Also metabolized by

multiple UDP-glucuronosyltransferase (UGTs). AGI–

16903 is also metabolized by multiple CYP450 isoenzymes

and UGTs. 89% eliminated in feces (34% as unchanged

drug); 11% eliminated in urine (1% as unchanged

drug).

Half-life: 137 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO unknown 4 hr unknown

Contraindications/Precautions

Contraindicated in: OB: May cause fetal harm;

Lactation: Avoid breast feeding.

Use Cautiously in: Rep: Women of reproductive

potential and men with female partners of reproductive

potential; Pedi: Safety and effectiveness not established.

Adverse Reactions/Side Effects

F and E: hypocalcemia, hypokalemia, hypophosphatemia.

GI:pappetite, diarrhea, dysgeusia,qbilirubin,

nausea, vomiting. GU:pfertility. Hemat: DIFFERENTIATION

SYNDROME, leukocytosis. Misc: tumor lysis syndrome.

Interactions

Drug-Drug: None reported.

Route/Dosage

PO (Adults): 100 mg once daily for at least 6 mo and

then continue until disease progression or unacceptable

toxicity.

Availability

Tablets: 50 mg, 100 mg.