Enasidenib

Enasidenib Uses, Dosage, Side Effects, Food Interaction and all others data.

Enasidenib is an orally available treatment for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with specific mutations in the isocitrate dehydrogenase 2 (IDH2) gene, which is a recurrent mutation detected in 12-20% of adult patients with AML . Patients eligible for this treatment are selected by testing the presence of IDH2 mutations in the blood or bone marrow. This small molecule acts as an allosteric inhibitor of mutant IDH2 enzyme to prevent cell growth, and it also has shown to block several other enzymes that play a role in abnormal cell differentiation. First developed by Agios Pharmaceuticals and licensed to Celgene, enasidenib was approved by U.S. Food and Drug Administration on August 1, 2017.

In a study involving adult patients with relapsed or refractory AML, overall response rate of 40.3% was achieved in enasidenib therapy which was associated with cellular differentiation and maturation, typically without evidence of aplasia . Enasidenib is not shown to cause QTc prolongation.

Enasidenib
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Enasidenib
Availability	Prescription only
Generic	Enasidenib
Enasidenib Other Names	Enasidenib
Related Drugs	Venclexta, vincristine, venetoclax, azacitidine, cytarabine, daunorubicin
Weight	100mg, 50mg
Type	Oral tablet
Formula	C₁₉H₁₇F₆N₇O
Weight	Average: 473.383 Monoisotopic: 473.139877173
Protein binding	In vitro, human plasma protein binding of enasidenib is 98.5% and 96.6% for its metabolite AGI-16903. Both the parent drug and its main metabolite are not reported to be substrates of MRP2, OAT1, OAT3, OATP1B1, OATP1B3, and OCT2. AGI-16903 is a substrate for both P-glycoprotein and BCRP .
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Enasidenib is an isocitrate dehydrogenase-2 inhibitor used to treat relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 mutation.

Indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation.

Enasidenib is also used to associated treatment for these conditions: Refractory Acute Myelogenous Leukemia (AML), Relapsed Acute Myelogenous Leukemia (AML)

How Enasidenib works

Enasidenib is a selective inhibitor of IDH2, a mitochondria-localized enzyme involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation and DNA modification . Wild-type IDH proteins play a cruicial role in the Krebs/citric acid cycle where it catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate. In comparison, mutant forms of IDH2 enzyme mediates a neomorphic activity and catalyze reduction of α-KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked cellular differentiation of hematopoietic progenitor cells . Enasidenib primarily targets the mutant IDH2 variants R140Q, R172S, and R172K with higher potency than the wild type enzyme form . Inhibition of the enzyme leads to decreased levels of 2-hydroxyglutarate (2-HG) and promotion of proper differentiation and clonal proliferation of cells of the myeloid lineage .

Toxicity

Enasidenib is not clastogenic or mutagenic in vitro. In vitro repeat-dose toxicity studies, enasidenib treatment induced changes in male and female reproductive systems including seminiferous tubular degeneration, hypospermia, atrophy of the seminal vesicle and prostate, decreased corpora lutea and increased atretic follicles in the ovaries, and atrophy in the uterus .

Food Interaction

Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of enasidenib; however, CYP3A4 is one of many enzymes involved in enasidenib metabolism.
Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of enasidenib; however, CYP3A4 is one of many enzymes involved in enasidenib metabolism.
Take at the same time every day.
Take with a full glass of water.
Take with or without food.

Enasidenib Disease Interaction

Moderate: hyperbilirubinemia

Volume of Distribution

The mean volume of distribution is 55.8L .

Elimination Route

Following a single oral dose of 100mg enasidenib, the peak plasma concentration of 1.3 mcg/mL is reached at 4 hours after ingestion. The absolute bioavailability is aproximately 57% and the steady-state plasma levels are reached within 29 days of once-daily dosing .

Half Life

Enasidenib has a terminal half-life of 137 hours .

Clearance

Enasidenib displays a mean total body clearance (CL/F) of 0.74 L/hour .

Elimination Route

Elimination of enasidenib involves 89% of fecal excretion and 11% of renal excretion. Unchanged drug accounts for 34% and 0.4% of the total drug detected in the feces and urine, respectively .