olutasidenib

Contraindicated in:

Severe renal impairment or end-stage renal disease;
Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Mild or moderate hepatic impairment (may have ↑ risk of differentiation syndrome);
Pedi: Safety and effectiveness not established in children;
Geri: ↑risk of hepatotoxicity and hypertension in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash

GI: ↑lipase, ↑liver enzymes, abdominal pain, constipation, diarrhea, hyperbilirubinemia, mucositis, nausea, vomiting

GU: ↑serum creatinine

Hemat: differentiation syndrome, leukocytosis, lymphocytosis

Metab: ↓appetite, hyperuricemia

MS: arthralgia

Neuro: fatigue, headache

Resp: cough, dyspnea

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inducers, including rifampin, and moderate CYP3A4 inducers may ↓ levels and effectiveness; avoid concurrent use.
May ↓ levels and effectiveness of CYP3A4 substrates; avoid concurrent use.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Availability ⬆ ⬇

Capsules: 150 mg

Route/Dosage ⬆ ⬇

PO (Adults ): 150 mg twice daily until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits the mutant IDH1 enzyme. Susceptible IDH1 mutations can lead to ↑ levels of 2-hydroxyglutarate in leukemia cells, which can ultimately lead to impaired hematopoietic differentiation.

Therapeutic effects:

Induction of complete remission or complete remission with partial hematologic recovery.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: isocitrate dehydrogenase-1 inhibitor

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration; absorption ↑ by high-fat meals.

Distribution: Extensively distributed to tissues.

Protein Binding: 93%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme, with minor contributions from the CYP1A2, CYP2C8, CYP2C9, and CYP2C19 isoenzymes. Primarily excreted in feces (75%; 35% as unchanged drug), with 17% excreted in urine (1% as unchanged drug).

Half-Life: 67 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4 hr	12 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Instruct patient that if vomiting occurs, omit dose and take next scheduled dose. Take missed doses as soon as remembered and ≥8 hr prior to next dose. Advise patient to read Patient Information before starting therapy.
Advise patient of the risk of developing differentiation syndrome as early as 1 day after initiation and up to 18 mo after starting therapy. Advise patient to notify health care professional immediately for fever, cough, difficulty breathing, ↓ urinary output, ↓ BP, weight gain, or swelling of arms or legs.
Advise patient to notify health care professional immediately with signs or symptoms of hepatotoxicity (right upper abdominal discomfort, dark urine, jaundice, anorexia, fatigue).
Advise patient to notify health care professional with GI reactions (nausea, vomiting, constipation, diarrhea, abdominal pain, mucositis) to seek guidance on symptom management.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: May cause fetal harm. Women of reproductive potential should notify health care professional if pregnancy is planned or suspected and to not breastfeed during therapy and for 2 wk after last dose.

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Indications ⬇

Contraind./Precautions ⬆ ⬇