Relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation.
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.
Promotion of complete remission and reduction in need for transfusions.
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)
- 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: ↓ appetite, diarrhea, dysgeusia, ↑ bilirubin, nausea, vomiting
GU: ↓ fertility
Hemat: DIFFERENTIATION SYNDROME, leukocytosis
Misc: tumor lysis syndrome
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
PO: (Adults) 100 mg once daily for at least 6 mo and then continue until disease progression or unacceptable toxicity.
Tablets: 50 mg, 100 mg
- Assess for signs and symptoms of differentiation syndrome (fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, hepatic, renal, or multi-organ dysfunction). If syndrome is suspected, start corticosteroid therapy and hemodynamic monitoring until symptom resolution. If severe pulmonary symptoms requiring intubation or ventilator support, and/or renal dysfunction persist >48 hours after initiation of corticosteroids, interrupt therapy. Resume enasidenib when signs and symptoms improve to ≤Grade 2.
Lab Test Considerations: Verify negative pregnancy test prior to starting therapy.
- Monitor CBC and blood chemistries for leukocytosis and tumor lysis syndrome prior to starting therapy and monitor at least every 2 wk for at least first 3 mos during therapy. If noninfectious leukocytosis (WBC >30 × 109 /L), treat with hydroxyurea, using institutional protocol. If leukocytosis is not improved with hydroxyurea, interrupt therapy and resume at 100 mg daily when <WBC 30 × 109 /L.
- Monitor serum bilirubin periodically during therapy. If ↑ >3 × ULN sustained for ≥2 wk without ↑ ALT or AST or other hepatic disorders, decrease enasidenib dose to 50 mg/day. If bilirubin resolves to <2 × ULN, resume to 100 mg/day dose.
- Deficient knowledge, related to medication regimen (Patient/Family/Teaching)
- PO: Administer once daily without regard for food.
- Instruct patient to take enasifinib as directed at same time each day. If dose is missed, not taken at usual time, or vomited, take dose as soon as possible on same day. Then return to routine schedule.
- Advise patient to notify health care professional if signs and symptoms of differentiation syndrome (fever, cough or difficulty breathing, bone pain, rapid weight gain, swelling of their arms or legs) occur. May occur within first 10 days through 5 mo of therapy.
- Inform patient of risk of tumor lysis syndrome and advise of need to maintain fluid intake and frequent blood chemistry monitoring.
- Advise patient to notify health care professional if signs and symptoms of GI adverse reactions (diarrhea, nausea, vomiting, decreased appetite, changes in sense of taste) or elevated bilirubin (changes to color of skin or whites of eyes) occur.
- Rep: May be teratogenic. Advise female and male patients of reproductive potential to use effective contraception during and for at least 1 mo after last dose of enasidenib. Advise female patient not to breast feed during therapy and for at least 1 mo after last dose. Inform patients that enasidenib may impair fertility in male and female patients.
Promotion of complete remission and reduction in need for transfusions. Minimum therapy is 6 mo to allow time for clinical response.
Medicine Central™ is a quick-consult mobile and web resource that includes diagnosis, treatment, medications, and follow-up information on over 700 diseases and disorders, providing fast answers—anytime, anywhere. Learn more.