IDHIFA Dosage & Rx Info | Uses, Side Effects

Idhifa Generic Name & Formulations

Legal Class

General Description

Enasidenib 50mg, 100mg; tabs.

Pharmacological Class

Isocitrate dehydrogenase-2 (IDH2) inhibitor.

How Supplied

Tabs—30

Manufacturer

Celgene Corp

Generic Availability

Mechanism of Action

Enasidenib targets the mutant IDH2 variants R140Q, R172S, and R172K at approximately 40-fold lower concentrations than the wild-type enzyme in vitro. Inhibition of the mutant IDH2 enzyme by enasidenib led to decreased 2-hydroxyglutarate (2-HG) levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH2 mutated AML. In blood samples from patients with AML with mutated IDH2, enasidenib decreased 2-HG levels, reduced blast counts and increased percentages of mature myeloid cells.

Idhifa Indications

Indications

Treatment of adults with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.

Idhifa Dosage and Administration

Adult

Swallow whole. Take at same time each day. Initially 100mg once daily until disease progression or unacceptable toxicity; treat for a minimum of 6 months to allow time for response. Monitoring and dose modifications for toxicities: see full labeling.

Children

Not established.

Idhifa Contraindications

Not Applicable

Idhifa Boxed Warnings

Boxed Warning

Differentiation syndrome.

Idhifa Warnings/Precautions

Warnings/Precautions

Risk of differentiation syndrome (may be fatal if not treated). If differentiation syndrome is suspected, initiate oral or IV corticosteroids and hemodynamic monitoring until resolution; interrupt dose if severe pulmonary symptoms requiring intubation or ventilator support, and/or renal dysfunction persist >48hrs after corticosteroid initiation. Assess blood counts/chemistries for leukocytosis and tumor lysis syndrome prior to initiation; monitor at minimum of every 2 weeks for at least the first 3 months during therapy. Embryo-fetal toxicity. Advise to use effective non-hormonal contraception for females of reproductive potential, and males (w. female partners) should use effective contraception, during and for 2 months after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for at least 2 months after the last dose).

Idhifa Pharmacokinetics

Absorption

Absolute bioavailability: ~57%. Median time to maximum plasma concentration: 4 hours.

Distribution

Volume of distribution: 55.8 L. Plasma protein bound: 98.5%.

Metabolism

Multiple CYP450 enzymes (eg, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4), and by multiple UGTs (eg, UGT1A1, UGT1A3, UGT1A4, UGT1A9, UGT2B7, and UGT2B15).

Elimination

Fecal (89%), renal (11%). Half-life: 7.9 days. Total body clearance: 0.70 L/hour.

Idhifa Interactions

Interactions

Potentiates certain substrates of CYP1A2 (eg, caffeine) or CYP2C19; avoid. Potentiates certain OATP1B1, OATP1B3, and BCRP substrates; avoid; if unavoidable, decrease substrate dose. Potentiates certain P-gp substrates; monitor. Antagonizes certain CYP3A substrates (eg, antifungal agents); avoid. Antagonizes hormonal contraceptives; consider alternative methods.

Idhifa Adverse Reactions

Adverse Reactions

Nausea, vomiting, diarrhea, elevated bilirubin, decreased appetite; differentiation syndrome, leukocytosis, tumor lysis syndrome.

Idhifa Clinical Trials

See Literature

Idhifa Note