Idhifa

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 8/9/2021
Idhifa Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Idhifa?

Idhifa (enasidenib) tablets are an isocitrate dehydrogenase-2 inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.

What Are Side Effects of Idhifa?

Common side effects of Idhifa include:

Dosage for Idhifa

The dose of Idhifa is 100 mg orally once daily until disease progression or unacceptable toxicity.

What Drugs, Substances, or Supplements Interact with Idhifa?

Idhifa may interact with other drugs. Tell your doctor all medications and supplements you use.

Idhifa During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Idhifa; it may harm a fetus. Women and men of reproductive age are advised to use contraception while using Idhifa and for at least 1 month after the last dose. It is unknown if Idhifa passes into breast milk. Because of the potential for adverse reactions in nursing infants, breastfeeding is not recommended while using Idhifa and for at least 1 month after the last dose.

Additional Information

Our Idhifa (enasidenib) Tablets Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Idhifa Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Enasidenib can cause a condition called differentiation syndrome, which affects blood cells and can be fatal if not treated. This condition may occur within 10 days to 5 months after you start taking enasidenib.

Seek medical help right away if you have symptoms of differentiation syndrome:

  • fever, cough, trouble breathing;
  • bone pain;
  • rapid weight gain; or
  • swelling in your arms, legs, underarms, groin, or neck.

Call your doctor at once if you have any of these side effects:

  • dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • severe or ongoing vomiting or diarrhea; or
  • signs of tumor cell breakdown--tiredness, weakness, muscle cramps, nausea, vomiting, diarrhea, fast or slow heart rate, tingling in your hands and feet or around your mouth.

Common side effects may include:

  • nausea, vomiting, diarrhea;
  • loss of appetite; or
  • jaundice.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Idhifa (Enasidenib Tablets)

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What is leukemia? See Answer
Idhifa Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Differentiation Syndrome [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety evaluation of single-agent IDHIFA is based on 214 patients with relapsed or refractory AML who were assigned to receive 100 mg daily [see Clinical Studies]. The median duration of exposure to IDHIFA was 4.3 months (range 0.3 to 23.6). The 30-day and 60-day mortality rates observed with IDHIFA were 4.2% (9/214) and 11.7% (25/214), respectively.

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.

Overall, 92 of 214 patients (43%) required a dose interruption due to an adverse reaction; the most frequent adverse reactions leading to dose interruption were differentiation syndrome (4%) and leukocytosis (3%). Ten of 214 patients (5%) required a dose reduction due to an adverse reaction; no adverse reaction required dose reduction in more than 2 patients. Thirty-six of 214 patients (17%) permanently discontinued IDHIFA due to an adverse reaction; the most frequent adverse reaction leading to permanent discontinuation was leukocytosis (1%).

The most common adverse reactions (≥20%) of any grade were nausea, vomiting, diarrhea, elevated bilirubin and decreased appetite.

Adverse reactions reported in the trial are shown in Table 2.

Table 2: Adverse Reactions Reported in ≥10% (Any Grade) or ≥3% (Grade 3-5) of Patients with Relapsed or Refractory AML

Body System Adverse ReactionIDHIFA (100 mg daily)
N=214
All Grades
N=214 n (%)
≥Grade 3
N=214 n (%)
Gastrointestinal Disordersa
Nausea107 (50)11 (5)
Diarrhea91 (43)17 (8)
Vomiting73 (34)4 (2)
Metabolism and Nutrition Disorders
Decreased appetite73 (34)9 (4)
Tumor lysis syndrome b13 (6)12 (6)
Blood and Lymphatic System Disorders
Differentiation syndrome c29 (14)15 (7)
Noninfectious leukocytosis26 (12)12 (6)
Nervous System Disorders
Dysgeusia25 (12)0 (0)
a Gastrointestinal disorders observed with IDHIFA treatment can be associated with other commonly reported events such as abdominal pain, and weight decreased.
b Tumor lysis syndrome observed with IDHIFA treatment can be associated with commonly reported uric acid increased.
c Differentiation syndrome can be associated with other commonly reported events such as respiratory failure, dyspnea, hypoxia, pyrexia, peripheral edema, rash, or renal insufficiency.

Other clinically significant adverse reactions occurring in ≤10% of patients included:

Respiratory, Thoracic, and Mediastinal Disorders: Pulmonary edema, acute respiratory distress syndrome

Changes in selected post-baseline laboratory values that were observed in patients with relapsed or refractory AML are shown in Table 3.

Table 3: Most Common (≥20%) New or Worsening Laboratory Abnormalities Reported in Patients with Relapsed or Refractory AML

Parameter aIDHIFA (100 mg daily)
N=214
All Grades (%)Grade ≥3 (%)
Total bilirubin increased8115
Calcium decreased748
Potassium decreased4115
Phosphorus decreased278
a Includes abnormalities occurring up to 28 days after last IDHIFA dose, if new or worsened by at least one grade from baseline, or if baseline was unknown. The denominator varies based on data collected for each parameter (N=213 except phosphorous N=209).

Elevated Bilirubin

IDHIFA may interfere with bilirubin metabolism through inhibition of UGT1A1 [see CLINICAL PHARMACOLOGY]. Thirty-seven percent of patients (80/214) experienced total bilirubin elevations ≥2 x ULN at least one time. Of those patients who experienced total bilirubin elevations ≥2 x ULN, 35% had elevations within the first month of treatment, and 89% had no concomitant elevation of transaminases or other severe adverse events related to liver disorders. No patients required a dose reduction for hyperbilirubinemia; treatment was interrupted in 3.7% of patients, for a median of 6 days. Three patients (1.4%) discontinued IDHIFA permanently due to hyperbilirubinemia.

Noninfectious Leukocytosis

IDHIFA can induce myeloid proliferation resulting in a rapid increase in white blood cell count.

Tumor Lysis Syndrome

IDHIFA can induce myeloid proliferation resulting in a rapid reduction in tumor cells which may pose a risk for tumor lysis syndrome.

Read the entire FDA prescribing information for Idhifa (Enasidenib Tablets)

© Idhifa Patient Information is supplied by Cerner Multum, Inc. and Idhifa Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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