ivosidenib

High Alert

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 (as monotherapy or in combination with azacitidine).
Relapsed or refractory AML with a susceptible IDH1 mutation.
Relapsed or refractory myelodysplastic syndromes with a susceptible IDH1 mutation.
Previously treated, locally advanced, or metastatic cholangiocarcinoma with an IDH1 mutation

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
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.

Adv. Reactions/Side Effects ⬆ ⬇

CV: chest pain, hypotension, peripheral edema, QT interval prolongation

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: anemia, differentiation syndrome, leukocytosis

Metab: ↓appetite, ↓weight

MS: arthralgia, myalgia

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

Resp: cough, dyspnea, pleural effusion

Misc: fever, tumor lysis syndrome

Interactions ⬆ ⬇

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.

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

Acute Myeloid Leukemia or Myelodysplastic Syndromes

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.

Cholangiocarcinoma

PO (Adults ): 500 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor: 250 mg once 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 (2-HG) in leukemia cells, which can ultimately lead to impaired hematopoietic differentiation.

Therapeutic effects:

Induction of complete remission or complete remission with partial hematologic recovery in AML.
Induction of complete remission in myelodysplastic syndromes.
Improved progression free survival in cholangiocarcinoma.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: isocitrate dehydrogenase-1 inhibitor

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3 hr	24 hr

Patient/Family Teaching ⬆ ⬇

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, light-headedness, feeling faint), or Guillain-Barré 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 cause fetal harm. Advise females of reproductive potential to use effective nonhormonal contraception during therapy and to avoid breastfeeding during and for at least 1 mo after last dose. May decrease fertility in males and females.

Pronunciation ⬆ ⬇

Code ⬆

NDC Code

54864- DOTTIKON EXCLUSIVE SYNTHESIS AG
- 54864-720-
  - 54864-720-15- 20 kg in 1 DRUM (54864-720-15)

54864- DOTTIKON EXCLUSIVE SYNTHESIS AG
- 54864-720-
  - 54864-720-63- 20 kg in 1 DRUM (54864-720-63)

63285- Patheon Inc.
- 63285-800-
  - 63285-800-00- 11429 TABLET, FILM COATED in 1 DRUM (63285-800-00)

72694- Servier Pharmaceutical LLC
- 72694-617- TIBSOVO
  72694-617-60- 1 BOTTLE in 1 CARTON (72694-617-60) / 60 TABLET, FILM COATED in 1 BOTTLE

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Indications ⬇