enasidenib (Rx)

Brand and Other Names:Idhifa
  • Print

Dosing & Uses

AdultPediatricGeriatric

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 with or without food 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 enasidenib dosing if pulmonary symptoms (eg, intubation/ventilator support) and/or renal dysfunction persists for >48 hr post corticosteroid initiation
  • Resume enasidenib when signs/symptoms improve to ≤grade 2 (mild-moderate)

Noninfectious leukocytosis (WBC >30,000 mcL)

  • Initiate hydroxyurea, as per standard institutional guidelines
  • Interrupt enasidenib dosing if no improvement of leukocytosis after initiating hydroxyurea
  • Resume enasidenib 100 mg qDay when WBC <30,000 mcL

Bilirubin elevated >3x ULN

  • If sustained for ≥2 weeks without elevated AST/ALT or other hepatic disorders, reduce enasidenib to 50 mg/day
  • Resume enasidenib dosing 100 mg/day if bilirubin elevation resolves (≤2x ULN)

Other ≥grade 3 toxicities (eg, tumor lysis syndrome)

  • Interrupt enasidenib dosing until toxicity resolve ≤grade 2
  • If toxicities resolve (≤grade 1), resume enasidenib at 50 mg/day; may increase to 100 mg/day
  • If ≥grade 3 recurs, discontinue

Dosing Considerations

Assess baseline blood cell counts and chemistries for leukocytosis and tumor lysis syndrome prior to initiation of enasidenib; monitor at least q2week for at least first 3 months of treatment

Manage any abnormalities promptly (see Adverse Reactions)

Safety and efficacy not established

No dosage adjustment required

Next:

Adverse Effects

>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%)

Previous
Next:

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 10 days 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 (see Black Box Warnings)

Based on animal embryofetal toxicity studies, can cause embryofetal harm when administered to pregnant women (see Pregnancy)

Previous
Next:

Pregnancy

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

Animal data

  • In animal embryofetal toxicity studies, 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 enasidenib is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential risk to a fetus

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

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.

more...
Previous
Next:

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%)

Drug Interaction Studies

Clinical relevance of the potential for enasidenib to affect substrates of the following enzymes and transporters has not yet been determined

In vitro studies suggest enasidenib inhibits the activity of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and UGT1A1; enasidenib inhibits P-gp, BCRP, OAT1, OATP1B1, OATP1B3, and OCT2, but not MRP2 or OAT3; enasidenib induces CYP2B6 and CYP3A4

In vitro studies suggest the metabolite AGI-16903 inhibits the activity of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6; inhibits BCRP, OAT1, OAT3, OATP1B1, and OCT2

Coadministration of enasidenib with combined hormonal contraceptives may increase or decrease the concentrations; the potential clinical significance of this drug interaction is currently unknown

Previous
Next:

Administration

Oral Administration

Take once 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 a missed dose 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 68-77°F (20-25°C); excursions permitted to 59-86°F (15-30°C)

Keep bottle tightly closed with desiccant canister inside original bottle to protect from moisture

Previous
Next:

Images

Previous
Next:

Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
Additional Offers
Email to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Email Forms to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Previous