NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend ivosidenib (TIBSOVO®) in R/R AML with an IDH1 mutation1

TIBSOVO® offers convenient, once-daily oral dosing1

500 mg Tablets for Dosing
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TIBSOVO should be taken at about the same time each day.1

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If a dose is missed or not taken at the usual time, patients should take the missed dose as soon as possible and at least 12 hours prior to the next scheduled dose. They should return to the normal schedule the following day. They should not take 2 doses within 12 hours.1


If a dose is vomited, patients should not take a replacement dose; they should wait until the next scheduled dose is due.1

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TIBSOVO tablets should not be split, crushed, or chewed.1

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TIBSOVO can be taken with or without food but should not be taken with a high-fat meal because of an increase in ivosidenib concentration.1a

aAn example of a high-fat meal includes 2 eggs fried in butter, 2 strips of bacon, 2 slices of white bread with butter, 1 croissant with 1 slice of cheese, and 8 ounces of whole milk (approximately 1000 calories and 58 grams of fat).1

Drug-drug interactions1

Strong or moderate CYP3A4 inhibitors

  • Coadministration increased ivosidenib plasma concentrations, which may increase the risk of QTc interval prolongation
  • Consider alternative therapies that are not strong or moderate CYP3A4 inhibitors
  • If coadministration is unavoidable, reduce TIBSOVO to 250 mg once daily. If the strong inhibitor is discontinued, increase the TIBSOVO dose (after at least 5 half-lives of the strong CYP3A4 inhibitor) to the recommended dose of 500 mg once daily
  • Monitor patients for increased risk of QTc interval prolongation

Strong CYP3A4 inducers

  • Coadministration decreased ivosidenib plasma concentrations
  • Avoid coadministration

QTc-prolonging drugs

  • Coadministration may increase the risk of QTc interval prolongation
  • Avoid coadministration with TIBSOVO or replace with alternative therapies
  • If coadministration is unavoidable, monitor patients for increased risk of QTc interval prolongation

Effect of TIBSOVO on other drugs

  • Ivosidenib induces CYP3A4 and may induce CYP2C9
  • Coadministration will decrease concentrations of drugs that are sensitive CYP3A4 substrates and may decrease the concentrations of drugs that are sensitive CYP2C9 substrates
  • Use alternative therapies that are not sensitive substrates of CYP3A4 and CYP2C9
  • Do not administer with itraconazole or ketoconazole (CYP3A4 substrates) due to expected loss of antifungal efficacy
  • Coadministration may decrease the concentrations of hormonal contraceptives. Consider alternative methods of contraception
  • If coadministration with sensitive CYP3A4 substrates or CYP2C9 substrates is unavoidable, monitor patients for loss of therapeutic effect of these drugs

Managing adverse reactions1

  • Assess blood counts and blood chemistries prior to the initiation of TIBSOVO, at least once weekly for the first month, once every other week for the second month, and once monthly for the duration of therapy
  • Monitor blood creatine phosphokinase weekly for the first month of therapy
  • Monitor ECGs at least once weekly for the first 3 weeks of therapy and then at least once monthly for the duration of therapy. Manage any abnormalities promptly
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Differentiation syndrome

  • 19% of patients (34/179) experienced differentiation syndrome
    • Onset occurred as early as 1 day and up to 3 months after initiation and has been observed with or without concomitant leukocytosis
    • Symptoms included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased
    • 79% of patients who experienced differentiation syndrome (27/34) recovered after treatment or after dose interruption of TIBSOVO
  • If differentiation syndrome is suspected, administer systemic corticosteroids (eg, dexamethasone 10 mg IV every 12 hours) and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days
  • Interrupt TIBSOVO if severe signs and/or symptoms persist for more than 48 hours after initiation with systemic corticosteroids
  • Resume TIBSOVO when signs and symptoms improve to Grade 2 or lower
  • Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment
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Noninfectious leukocytosis

  • Initiate treatment with hydroxyurea, as per standard institutional practices, and leukapheresis if clinically indicated
  • Taper hydroxyurea only after leukocytosis improves or resolves
  • Interrupt TIBSOVO if leukocytosis is not improved with hydroxyurea, and then resume TIBSOVO at 500 mg daily when leukocytosis has resolved
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QTc prolongation

Of the 258 patients treated with TIBSOVO in the trial:

  • 9% had a QTc interval >500 msec
  • 14% had a >60 msec increase from baseline QTc interval
  • One patient developed ventricular fibrillation attributed to TIBSOVO

QTc interval >480 msec to 500 msec

  • Monitor and supplement electrolyte levels as clinically indicated
  • Review and adjust concomitant medications with known QTc interval–prolonging effects
  • Interrupt TIBSOVO
  • Restart TIBSOVO at 500 mg once daily after the QTc interval returns to ≤480 msec
  • Monitor ECGs at least weekly for 2 weeks following resolution of QTc prolongation

QTc interval >500 msec

  • Monitor and supplement electrolyte levels as clinically indicated
  • Review and adjust concomitant medications with known QTc interval–prolonging effects
  • Interrupt TIBSOVO
  • Resume TIBSOVO at a reduced dose of 250 mg once daily when QTc interval returns to within 30 msec of baseline or ≤480 msec
  • Monitor ECGs at least weekly for 2 weeks following resolution of QTc prolongation
  • Consider re-escalating the dose of TIBSOVO to 500 mg daily if an alternative etiology for QTc prolongation can be identified

QTc interval prolongation with signs/symptoms of life-threatening arrhythmia

  • Discontinue TIBSOVO permanently
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Guillain-Barré syndrome

  • <1% of patients treated with TIBSOVO (2/258) experienced Guillain-Barré syndrome
  • Monitor patients for onset of new signs or symptoms of motor and/or sensory neuropathy, such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing
  • Discontinue TIBSOVO permanently
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Other ≥Grade 3 toxicity considered related to treatment

  • Interrupt TIBSOVO until toxicity resolves to ≤Grade 2
  • Resume TIBSOVO at 250 mg once daily; may increase to 500 mg once daily if toxicities resolve to ≤Grade 1
  • If ≥Grade 3 toxicity recurs, discontinue TIBSOVO
Reference: 1. TIBSOVO [package insert]. Cambridge, MA: Agios Pharmaceuticals, Inc.; 2018.
 

INDICATION

TIBSOVO® (ivosidenib) is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

Indication & Important Safety Information

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.