• Newly-diagnosed acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation in patients who are 75 years old or who have comorbidities that prevent the use of intensive induction chemotherapy.
• Relapsed or refractory AML with a susceptible IDH1 mutation.

Contraindicated in:

• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Congenital long QT syndrome, HF, electrolyte abnormalities, or concurrent use of QT interval prolonging medications (↑ risk of QT interval prolongation)
• Severe renal impairment
• Severe hepatic impairment
• Pedi: Safety and effectiveness not established in children.

CV: QT INTERVAL PROLONGATION, chest pain, hypotension, peripheral edema.

Derm: pruritus, rash.

Endo: hyperuricemia.

F and E: hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia.

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

GU: ↑serum creatinine.

Hemat: differentiation syndrome, anemia, leukocytosis.

Metab: ↓appetite, ↓weight.

MS: arthralgia, myalgia.

Neuro: neuropathy, Guillain-Barré syndrome , dizziness, fatigue, headache.

Resp: cough, dyspnea, pleural effusion.

Misc: fever, tumor lysis syndrome.

Drug-Drug:

• QT interval prolonging drugs may ↑ risk of QT interval prolongation; avoid concurrent use.
• Moderate or strong CYP3A4 inhibitors, including fluconazole and itraconazole may ↑ levels and risk of toxicity; avoid concurrent use, if possible; if need to use, ↓ ivosidenib dose.
• Strong CYP3A4 inducers, including rifampin may ↓ levels and effectiveness; avoid concurrent use.
• May ↓ levels of CYP3A4 substrates, including itraconazole, ketoconazole, or hormonal contraceptives; avoid concurrent use.
• May ↓ levels of CYP2C9 substrates, including itraconazole; avoid concurrent use.

• Tablets: 250 mg;

• PO (Adults): 500 mg once daily until disease progression or unacceptable toxicity. In absence of disease progression or unacceptable toxicity, continue therapy for 6 mo. Concurrent use of strong CYP3A4 inhibitor — 250 mg once daily until disease progression or unacceptable toxicity. In absence of disease progression or unacceptable toxicity, continue therapy for 6 mo.

Tibsovo

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

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

Therapeutic Classification: antineoplastics

Pharmacologic Classification: isocitrate dehydrogenase-1 inhibitor

Absorption: Rapidly absorbed; absorption ↑ by high-fat meals.

Distribution: Extensively distributed to tissues.

Protein Binding: 92–96%.

Metabolism/Excretion: Primarily metabolized in the liver by the CYP3A4 isoenzyme. Primarily excreted in feces (77%; 67% as unchanged drug), 17% excreted in urine (10% as unchanged drug).

Half-life: 93 hr.

(plasma concentrations)

• Instruct patient to take ivosidenib as directed. Avoid taking with high fat meals. If vomiting occurs after taking dose, omit dose and take next dose when scheduled. Take missed doses as soon as remembered at least 12 hr from next dose; do not take 2 doses within 12 hr. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
• Advise patient to notify health care professional immediately if signs and symptoms of differentiation syndrome (fever, cough, low BP, rapid weight gain, trouble breathing, swelling of arms or legs, rash, decreased urination), QT interval prolongation (dizziness, lightheadedness, feeling faint), or Guillain-Barre syndrome (weakness or tingling feeling in legs, arms, or upper body; numbness and pain on one or both sides of body; changes in ability to see, touch, hear, or taste; burning or prickling sensation; difficulty breathing) occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Rep: May be teratogenic. Advise females of reproductive potential to use nonhormonal effective contraception during therapy and to avoid breastfeeding during and for at least 1 mo after last dose. May decrease fertility in males and females.

EYE-voe-SID-e-nib

NDC Code^*

• 71334- Agios Pharmaceuticals, Inc.
  • 71334-100- Tibsovo
    • 71334-100-01- 60 TABLET, FILM COATED in 1 BOTTLE (71334-100-01)