Dosage & Administration
100 mg orally once daily until disease progression or unacceptable toxicity (
The recommended dosage of IDHIFA is 100 mg taken orally once daily with or without food until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response.
Swallow tablets whole. Do not chew, split, or crush IDHIFA tablets. Administer IDHIFA tablets orally about the same time each day. If a dose of IDHIFA is vomited, missed, or not taken at the usual time, administer the dose as soon as possible on the same day, and return to the normal schedule the following day.
Idhifa Prescribing Information
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 is associated with rapid proliferation and differentiation of myeloid cells. While there is no diagnostic test for differentiation syndrome, symptoms in patients treated with IDHIFA included acute respiratory distress represented by dyspnea and/or hypoxia (68%) and need for supplemental oxygen (76%); pulmonary infiltrates (73%) and pleural effusion (45%); renal impairment (70%); fever (36%); lymphadenopathy (33%); bone pain (27%); peripheral edema with rapid weight gain (21%); and pericardial effusion (18%). Hepatic, renal, and multi-organ dysfunction have also been observed.
Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, in as early as 1 day and up to 5 months after IDHIFA initiation.
If differentiation syndrome is suspected, initiate oral or intravenous corticosteroids (e.g., dexamethasone 10 mg every 12 hours) and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid treatment. 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
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
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.
| aGastrointestinal disorders observed with IDHIFA treatment can be associated with other commonly reported events such as abdominal pain, and weight decreased. bTumor lysis syndrome observed with IDHIFA treatment can be associated with commonly reported uric acid increased. cDifferentiation syndrome can be associated with other commonly reported events such as respiratory failure, dyspnea, hypoxia, pyrexia, peripheral edema, rash, or renal insufficiency. | ||
IDHIFA (100 mg daily) N=214 | ||
Body System Adverse Reaction | All Grades N=214 n (%) | ≥Grade 3 N=214 n (%) |
Gastrointestinal Disorders a | ||
Nausea | 107 (50) | 11 (5) |
Diarrhea | 91 (43) | 17 (8) |
Vomiting | 73 (34) | 4 (2) |
Metabolism and Nutrition Disorders | ||
Decreased appetite | 73 (34) | 9 (4) |
Tumor lysis syndromeb | 13 (6) | 12 (6) |
Blood and Lymphatic System Disorders | ||
Differentiation syndromec | 29 (14) | 15 (7) |
Noninfectious leukocytosis | 26 (12) | 12 (6) |
Nervous System Disorders | ||
Dysgeusia | 25 (12) | 0 (0) |
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.
IDHIFA (100 mg daily) N=214 | ||
|---|---|---|
Parametera | All Grades (%) | Grade ≥3 (%) |
| aIncludes 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). | ||
Total bilirubin increased | 81 | 15 |
Calcium decreased | 74 | 8 |
Potassium decreased | 41 | 15 |
Phosphorus decreased | 27 | 8 |
IDHIFA may interfere with bilirubin metabolism through inhibition of UGT1A1
IDHIFA can induce myeloid proliferation resulting in a rapid increase in white blood cell count.
IDHIFA can induce myeloid proliferation resulting in a rapid reduction in tumor cells which may pose a risk for tumor lysis syndrome.
The following adverse reactions occurred in other clinical trials of IDHIFA at the recommended dosage: neutropenia, thrombocytopenia, anemia, stomatitis, renal failure, fatigue, dyspnea, and QT prolongation.
IDHIFA is 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 (
IDHIFA is 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.
100 mg orally once daily until disease progression or unacceptable toxicity (
The recommended dosage of IDHIFA is 100 mg taken orally once daily with or without food until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response.
Swallow tablets whole. Do not chew, split, or crush IDHIFA tablets. Administer IDHIFA tablets orally about the same time each day. If a dose of IDHIFA is vomited, missed, or not taken at the usual time, administer the dose as soon as possible on the same day, and return to the normal schedule the following day.
IDHIFA is available in the following tablet strengths:
• 50 mg enasidenib tablet: Pale yellow to yellow oval-shaped film-coated tablet debossed "ENA" on one side and "50" on the other side.• 100 mg enasidenib tablet: Pale yellow to yellow capsule-shaped film-coated tablet debossed "ENA" on one side and "100" on the other side.
There are no data on the presence of enasidenib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. 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.
None.