Dosing & Uses
Dosage Forms & Strengths
tablet
- 50mg
- 100mg
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 until disease progression or unacceptable toxicity
In patients without disease progression or unacceptable toxicity, treat for ≥6 months to allow time for clinical response
Dosage Modifications
Differentiation syndrome
- If differentiation syndrome suspected, administer systemic corticosteroids; initiate hemodynamic monitoring
- Interrupt therapy if pulmonary symptoms (eg, intubation/ventilator support) and/or renal dysfunction persists for >48 hr post corticosteroid initiation
- Resume once signs/symptoms improve to Grade ≤2 (mild-moderate)
Noninfectious leukocytosis (WBC >30,000 mcL)
- Initiate hydroxyurea, as per standard institutional guidelines
- Interrupt therapy if no improvement of leukocytosis after initiating hydroxyurea
- Resume at 100 mg/day when WBC <30,000 mcL
Bilirubin elevated >3x ULN
- If sustained for ≥2 weeks without elevated AST/ALT or other hepatic disorders, reduce dose to 50 mg/day
- Resume at 100 mg/day if bilirubin elevation resolves to ≤2x ULN
Other Grade ≥3 toxicities (eg, tumor lysis syndrome)
- Interrupt therapy until toxicity resolve Grade ≤2
- If toxicities resolve (Grade ≤1), resume at 50 mg/day; may increase to 100 mg/day
- If Grade≥3 recurs, discontinue
Dosing Considerations
Monitoring parameters
- Assess baseline blood cell counts and chemistries for leukocytosis and tumor lysis syndrome before initiation; monitor at least q2week for at least first 3 months of treatment
Patient selection
- Select patients for treatment based on presence of IDH2 mutations in the blood and bone marrow
- Information is available at: http://www.fda.gov/CompanionDiagnostics
Safety and efficacy not established
No dosage adjustment required
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (0)
Minor (5)
- dienogest/estradiol valerate
enasidenib, dienogest/estradiol valerate. unknown mechanism. Minor/Significance Unknown. Coadministration of enasidenib may increase or decrease the concentrations of combined hormonal contraceptives. Clinical significance of this interaction is unknown.
- drospirenone
enasidenib, drospirenone. unknown mechanism. Minor/Significance Unknown. Coadministration of enasidenib may increase or decrease the concentrations of combined hormonal contraceptives. Clinical significance of this interaction is unknown.
- ethinylestradiol
enasidenib, ethinylestradiol. unknown mechanism. Minor/Significance Unknown. Coadministration of enasidenib may increase or decrease the concentrations of combined hormonal contraceptives. Clinical significance of this interaction is unknown.
- levonorgestrel oral
enasidenib, levonorgestrel oral. unknown mechanism. Minor/Significance Unknown. Coadministration of enasidenib may increase or decrease the concentrations of combined hormonal contraceptives. Clinical significance of this interaction is unknown.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
enasidenib, levonorgestrel oral/ethinylestradiol/ferrous bisglycinate. unknown mechanism. Minor/Significance Unknown. Coadministration of enasidenib may increase or decrease the concentrations of combined hormonal contraceptives. Clinical significance of this interaction is unknown.
Adverse Effects
>10%
All grades
- Total bilirubin increased (81%)
- Calcium decreased (74%)
- Nausea (50%)
- Diarrhea (43%)
- Potassium decreased (41%)
- Vomiting (34%)
- Decreased appetite (34%)
- Phosphorus decreased (27%)
- Differentiation syndrome (14%)
- Noninfectious leukocytosis (12%)
- Dysgeusia (12%)
Grade 3 or 4
- Total bilirubin increased (15%)
- Potassium decreased (15%)
1-10%
All grades
- Pulmonary edema (≤10%)
- Acute respiratory distress syndrome (≤10%)
- Tumor lysis syndrome (6%)
Grade 3 or 4
- Diarrhea (8%)
- Calcium decreased (8%)
- Phosphorus decreased (8%)
- Differentiation syndrome (7%)
- Tumor lysis syndrome (6%)
- Noninfectious leukocytosis (6%)
- Nausea (5%)
- Decreased appetite (4%)
- Vomiting (2%)
Warnings
Black Box Warnings
Differentiation syndrome
- In the clinical trial, 14% of patients treated with enasidenib experienced symptoms of differentiation syndrome, which can be fatal if not treated
- Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multiorgan dysfunction
- Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 1 day and at up to 5 months after initiating enasidenib
- If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution
- Taper corticosteroids only after resolution of symptoms; differentiation syndrome symptoms may recur with premature discontinuation of corticosteroids
- If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for >48 hr after initiation of corticosteroids, interrupt enasidenib until signs and symptoms are no longer severe
- Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended
Contraindications
None
Cautions
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
Drug interaction overview
-
OATP1B1, OATP1B3, and BCRP substrates
- Enasidenib is an OATP1B1, OATP1B3, and BCRP inhibitor
- Coadministration with OATP1B1, OATP1B3, and BCRP substrates will increase effects and toxicities of these substrates
- Decrease dose of OATP1B1, OATP1B3, and BCRP substrate(s) as recommended in respective prescribing information, and as clinically indicated
-
P-gp substrates
- Enasidenib is a P-gp inhibitor
- Coadministration with P-gp substrates will increase effects and toxicities of these substrates
- For a sensitive P-gp substrate may lead to serious adverse reactions, decrease dose or modify dosing frequency of such a P-gp substrate and monitor for adverse reactions as recommended in respective prescribing information
Pregnancy
Pregnancy
Based on animal embryofetal toxicity studies, fetal harm may occur when administered to pregnant females
No data available on use in pregnant females to inform a drug-associated risk of major birth defects and miscarriage
Animal data
- Oral administration of enasidenib to pregnant rats and rabbits during organogenesis was associated with embryofetal mortality and alterations to growth starting at 0.1 times the steady state clinical exposure based on the AUC at the recommended human dosage
- If used during pregnancy, or if patient becomes pregnant while taking this drug, advise of the potential risk to a fetus
Infertility
- Based on findings in animals, fertility may be impaired in females and males of reproductive potential
- Unknown whether effects on fertility are reversible
Contraception
Females of reproductive potential
- Avoid becoming pregnant while receiving enasidenib
- Use effective contraception during treatment with enasidenib and for at least 2 month after the last dose
- Coadministration of enasidenib may increase or decrease the concentrations of combined hormonal contraceptives; the clinical significance is unknown at this time
Males with female partners of reproductive potential
- Use effective contraception during treatment with enasidenib and for at least 2 month after the last dose
Lactation
There are no data on the presence of enasidenib or its metabolites in human milk, effects on the breastfed infants, or effects on milk production
Advise women not to breastfeed during treatment with enasidenib and for at least 2 months after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
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
Absorption
Peak plasma concentration: 1.3 mcg/mL (single dose); 13 mcg/mL (steady state)
Peak plasma time: 4 hr
Bioavailability: ~ 57%
Time to steady state: 29 days
Distribution
Vd: 55.8 L
Protein bound, in vitro: 98.5% (enasidenib); 96.6% (metabolite; AGI-16903)
Metabolism
Metabolized by multiple CYP enzymes (eg, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and by multiple UGTs (eg, UGT1A1, UGT1A3, UGT1A4, UGT1A9, UGT2B7, and UGT2B15)
Metabolite AGI-16903 metabolized by similar enzymes (eg, CYP1A2, CYP2C19, CYP3A4, UGT1A1, UGT1A3, and UGT1A9)
Elimination
Half-life: 137 hr
Total body clearance: 0.74 L/hr
Excretion: feces (89%); urine (11%)
Administration
Oral Administration
Take at the same time each day; may be taken with or without food
Do not chew or split the tablet; swallow tablets whole with a cup of water
Missed dose
- Administer as soon as possible on the same day
- If close to the following dose, skip missed dose and take current dose
- Do not take 2 doses at the same time
Storage
Store at room temperature at 68-77ºF (20-25ºC); excursions permitted to 59-86ºF (15-30ºC)
Keep bottle tightly closed with desiccant canister inside original bottle to protect from moisture
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Idhifa oral - | 100 mg tablet |  | |
| Idhifa oral - | 50 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
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