EYE-voe-SID-e-nib

Therapeutic Classification: antineoplastics

Pharmacologic Classification: isocitrate dehydrogenase-1 inhibitor

• 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.

• 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.

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)

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.

• 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.

• Tablets: 250 mg;

• Monitor ECG at least weekly for first 3 wks of therapy, then at least monthly during therapy. If QTc interval >480 to 500 msec, monitor and supplement electrolyte levels as needed. Adjust concomitant medications with QTc interval-prolonging effects. Hold ivosidenib; resume at 500 mg daily after QTc interval <480 msec. Monitor ECGs at least weekly for 2 wks following resolution of QTc interval prolongation. If QT interval >500 msec, monitor and supplement electrolyte levels as needed. Adjust concomitant medications with QTc interval-prolonging effects. Hold ivosidenib; resume 250 mg daily after QTc interval returns to within 30 msec of baseline or 480 msec. Monitor ECGs at least weekly for 2 wks following resolution. Consider re-escalating dose to 500 mg daily if an cause for QTc interval prolongation identified. If QTc interval prolongation with signs and symptoms of life threatening arrhythmia occurs, discontinue ivosidenib permanently.
• Monitor for signs and symptoms of differentiation syndrome (noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, increased creatinine) during therapy. If suspected, administer systemic corticosteroids (dexamethasone 10 mg IV every 12 hr or equivalent) and begin hemodynamic monitoring until symptom resolution and for a minimum of 3 days. Hold ivosidenib if severe signs and symptoms persist >48 hr after starting corticosteroids. Resume therapy when signs and symptoms Grade 2.
• Monitor for onset of new signs or symptoms of motor and/or sensory neuropathy (unilateral or bilateral weakness, sensory alterations, paresthesias, difficulty breathing). May cause Guillain-Barre syndrome. If diagnosis is confirmed, permanently discontinue ivosidenib.

• Patient selection is based on presence of IDH1 mutations in blood or bone marrow. Information on FDA-approved tests for the detection of IDH1 mutations in AML is available at www.fda.gov/CompanionDiagnostics.
  • Assess CBC and blood chemistries before starting therapy, at least weekly for 1st mo, once every other week for 2nd mo, and monthly during therapy.
  • Monitor blood creatine kinase weekly for 1st mo of therapy.
  • If noninfectious leukocytosis (WBC >25 × 10⁹/L or absolute increase in total WBC >15 × 10⁹/L from baseline occurs, treat with hydroxyurea and leukapheresis if indicated. Taper hydroxyurea only after leukocytosis improves or resolves. If leukocytosis not improved with hydroxyurea, hold ivosidenib and resume at 500 mg daily when leukocytosis resolved.

• PO: Administer once daily, at same time each day, without regard to food. Avoid taking with high fat meal. Swallow tablets whole; do not crush, break or chew.

• 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.

• Continue therapy for at least 6 mo to allow time for clinical response.

Tibsovo

• Deficient knowledge, Relate med (Patient/Family Teaching).

NDC Code^*

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