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Indication
IDHIFA® (enasidenib) is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 mutation as detected by an FDA-approved test.

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SAFETY

Safety Profile

IDHIFA® OFFERS A DIFFERENT SAFETY PROFILE IN R/R AML

ADVERSE REACTIONS (ARs) REPORTED IN ≥10% (ANY GRADE) OR ≥3% (GRADES 3-5) OF PATIENTS WITH R/R AML

Body System Adverse Reactions Table
Body System Adverse Reactions Table

aGastrointestinal disorders observed with IDHIFA® treatment can be associated with other commonly reported events, such as abdominal pain and weight decrease.

bTLS observed with IDHIFA® treatment can be associated with commonly reported uric acid increase.

cDifferentiation syndrome can be associated with other commonly reported events such as respiratory failure, dyspnea, hypoxia, pyrexia, peripheral edema, rash, or renal insufficiency.

MOST COMMON (≥20%) NEW OR WORSENING LABORATORY ABNORMALITIES REPORTED IN PATIENTS WITH R/R AML

Laboratory Abnormalities Table
Laboratory Abnormalities Table

DOSE MODIFICATIONS IN THE CLINICAL TRIAL

Frequency of Dose Interruption, Reduction, and Discontinuation in Clinical Trial
Frequency of Dose Interruption, Reduction, and Discontinuation in Clinical Trial

ADDITIONAL ANALYSIS: THE FREQUENCY OF ARs OVER TIME

ARs REPORTED IN ≥10% (ANY GRADE) OR ≥3% (GRADES 3-5) OF PATIENTS WITH R/R AML1

Adverse Reaction Frequency Graph
Adverse Reaction Frequency Graph

Differentiation Syndrome

DIFFERENTIATION SYNDROME MAY OCCUR WITH IDHIFA®

Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells. It may be life-threatening or fatal if not treated.

Frequency of Differentiation Syndrome
Frequency of Differentiation Syndrome

For appropriate patient management

IT IS IMPORTANT TO RECOGNIZE AND INITIATE TREATMENT FOR DIFFERENTIATION SYNDROME

Initial and Subsequent Differentiation Syndrome Management Tables
Initial and Subsequent Differentiation Syndrome Management Tables

NONINFECTIOUS LEUKOCYTOSIS

Initial and Subsequent Noninfectious Leukocytosis Management Tables
Initial and Subsequent Noninfectious Leukocytosis Management Tables

Additional Warnings, Precautions, & ARs

ADDITIONAL WARNINGS, PRECAUTIONS, & ARs

SELECTED WARNINGS AND PRECAUTIONS

Frequency of Noninfectious Leukocytosis and Tumor Lysis Syndrome
Frequency of Noninfectious Leukocytosis and Tumor Lysis Syndrome
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  1. Data on file, Celgene Corporation. Summit, New Jersey.

WARNING: DIFFERENTIATION SYNDROME

Patients treated with IDHIFA have 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 multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome, which may be life-threatening or fatal if not treated. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, in as early as 1 day and up to 5 months after IDHIFA initiation. Symptoms in patients treated with IDHIFA included acute respiratory distress represented by dyspnea and/or hypoxia and need for supplemental oxygen; pulmonary infiltrates and pleural effusion; renal impairment; fever; lymphadenopathy; bone pain; peripheral edema with rapid weight gain; and pericardial effusion. Hepatic, renal, and multi-organ dysfunction have also been observed. If differentiation syndrome is suspected, initiate systemic corticosteroids and hemodynamic monitoring until improvement. 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 more than 48 hours after initiation of corticosteroids, interrupt IDHIFA until signs and symptoms are no longer severe. Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended.

Embryo-Fetal Toxicity: Based on animal embryo-fetal toxicity studies, IDHIFA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential and males with female partners of reproductive potential to use effective non-hormonal contraception during treatment with IDHIFA and for 2 months after the last dose. Advise pregnant women of the potential risk to the fetus.

ADVERSE REACTIONS

  • The most common adverse reactions (≥20%) included total bilirubin increased (81%), calcium decreased (74%), nausea (50%), diarrhea (43%), potassium decreased (41%), vomiting (34%), decreased appetite (34%), and phosphorus decreased (27%)
  • The most frequently reported ≥Grade 3 adverse reactions (≥5%) included total bilirubin increased (15%), potassium decreased (15%), phosphorus decreased (8%), calcium decreased (8%), diarrhea (8%), differentiation syndrome (7%), non-infectious leukocytosis (6%), tumor lysis syndrome (6%), and nausea (5%)
  • Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions (≥2%) were leukocytosis (10%), diarrhea (6%), nausea (5%), vomiting (3%), decreased appetite (3%), tumor lysis syndrome (5%), and differentiation syndrome (8%). Differentiation syndrome events characterized as serious included pyrexia, renal failure acute, hypoxia, respiratory failure, and multi-organ failure

DRUG INTERACTIONS

Certain CYP1A2 CYP2C19 Substrates

Avoid concomitant use with IDHIFA unless otherwise recommended in the Prescribing Information for CYP1A2, CYP2C19 substrates where minimal concentration changes may lead to serious adverse reactions. Consider reducing the frequency of caffeine intake from various food and beverages in a 24-hour period while taking IDHIFA because IDHIFA may increase the effect of caffeine in patients who are sensitive to it. Enasidenib is a CYP1A2, CYP2C19 inhibitor. Concomitant use of IDHIFA increases the exposure of CYP1A2, CYP2C19 substrates, which may increase the risk of adverse reactions related to the substrates.

Certain CYP3A substrates

Avoid concomitant use with IDHIFA unless otherwise recommended in the Prescribing Information for CYP3A substrates where minimal concentration changes may lead to reduced efficacy. Do not administer IDHIFA with anti-fungal agents that are substrates of CYP3A due to expected loss of antifungal efficacy. Co-administration of IDHIFA may decrease the concentrations of hormonal contraceptives. Consider alternative methods of contraception in patients receiving IDHIFA. Enasidenib is a CYP3A inducer. Concomitant use of IDHIFA decreases the exposure of CYP3A substrates, which may reduce the efficacy of the substrates.

Certain OATP1B1, OATP1B3, and BCRP Substrates

Avoid coadministration of IDHIFA with OATP1B1, OATP1B3, and BCRP substrates, for which minimal concentration changes may lead to serious toxicities. If coadministration cannot be avoided, decrease the OATP1B1, OATP1B3, and BCRP substrates dosage(s) in accordance with the respective Prescribing Information. Enasidenib is an OATP1B1, OATP1B3, and BCRP transporter inhibitor. Concomitant use of IDHIFA increases the exposure of OATP1B1, OATP1B3, and BCRP, which may increase the risk of adverse reactions related to these substrates.

Certain P-glycoprotein (P-gp) Substrates

When coadministered with IDHIFA, follow recommended P-gp substrates Prescribing Information and monitor more frequently for adverse reactions related to these substrates. Enasidenib is a P-gp transporter inhibitor. Concomitant use of IDHIFA increases the exposure of P-gp substrates, which may increase the risk of adverse reactions related to the substrates.

LACTATION

Because of the potential for adverse reactions in the breastfed child, advise women not to breastfeed during treatment with IDHIFA and for 2 months after the last dose.

  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.1.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed March 4, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
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  9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.1.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed March 4, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  10. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209-2221.
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  6. Data on file, Celgene Corporation. Summit, New Jersey.
  1. Data on file, Celgene Corporation. Summit, New Jersey.
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03/24  2018-US-2300021