Idhifa

Idhifa (enasidenib) is a prescription medicine used to treat people with acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation whose disease has come back or has not improved after previous treatment(s). It is not known if Idhifa is safe and effective in children.

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.

The most common side effects of Idhifa include:

• nausea
• vomiting
• diarrhea
• jaundice
• decreased appetite

Tell your healthcare provider if you have any changes to the color of your skin or the whites of your eyes.

Your healthcare provider will monitor you for side effects during treatment and may tell you to stop taking Idhifa if you develop certain side effects.

These are not all the possible side effects of Idhifa.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Patient Selection

• Select patients for the treatment of AML with Idhifa based on the presence of IDH2 mutations in the blood or bone marrow. Information on FDA-approved tests for the detection of IDH2 mutations in AML is available at https://www.fda.gov/CompanionDiagnostics.

Recommended Dosage

• 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.
• Do not 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.

Monitoring and Dosage Modifications for Toxicities

Assess blood counts and blood chemistries for leukocytosis and tumor lysis syndrome prior to the initiation of Idhifa and monitor at a minimum of every 2 weeks for at least the first 3 months during treatment. Manage any abnormalities promptly.

Interrupt dosing or reduce dose for toxicities. See Table 1 for dosage modification guidelines.

Table 1: Dosage Modifications for Idhifa-Related Toxicities

Effect of Idhifa on Other Drugs

OATP1B1, OATP1B3, and BCRP Substrates

• Idhifa is an OATP1B1, OATP1B3, and BCRP inhibitor. Coadministration of Idhifa increases the exposure of OATP1B1, OATP1B3, and BCRP substrates, which may increase the incidence and severity of adverse reactions of these substrates.
• Decrease the dosage of OATP1B1, OATP1B3, and BCRP substrate(s) as recommended in the respective prescribing information, and as clinically indicated.

Certain P-glycoprotein (P-gp) Substrates

• Idhifa is a P-gp inhibitor. Coadministration of Idhifa increases the exposure of P-gp substrates, which may increase the incidence and severity of adverse reactions of these substrates.
• For a P-gp substrate where small concentration changes may lead to serious adverse reactions, decrease the dose or modify the dosing frequency of such a P-gp substrate and monitor for adverse reactions as recommended in the respective prescribing information.

• Based on animal embryo-fetal toxicity studies, Idhifa can cause fetal harm when administered during pregnancy.
• There are no available data on Idhifa use to inform a drug-associated risk of major birth defects and miscarriage.
• 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 at least 2 months after the last dose.