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Recommended dose

Single-agent TIBSOVO® (ivosidenib tablets) offers convenient, once-daily oral dosing and can be taken at home1

500 mg (2 x 250 mg film-coated tablets) Pills example Tablets not shown at actual size.

Taken orally, once daily until disease progression or unacceptable toxicity

Treatment with TIBSOVO has not been studied in patients with preexisting severe renal or hepatic impairment. For patients with preexisting severe renal or hepatic impairment, consider the risks and potential benefits before initiating treatment with TIBSOVO.1

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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.1,a

a An 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

For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response.1

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Dose Intensity

In clinical trials, median relative dose intensity was 98.7% across all patients2

  • Relative dose intensity is the amount of therapy taken over a specific period of time in relation to what was prescribedb
  • There were very few occurrences of missed or incorrect doses, indicating excellent overall compliance

b Relative Dose Intensity (%) was calculated as: [Actual Dose Intensity] / [Planned Dose Intensity]. Actual Dose Intensity (mg/day) was calculated as: [Actual Total Dose] /[Duration of Treatment in days]. Planned Dose Intensity (mg/day) was calculated as: [Planned Total Dose] / [Planned Duration].

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Managing adverse reactions

Managing adverse reactions to TIBSOVO

  • 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 therapy1
  • Monitor blood creatine phosphokinase weekly for the first month of therapy1
  • Obtain an electrocardiogram (ECG) prior to treatment initiation. 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 promptly1
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Differentiation syndrome1

  • 25% of patients with newly diagnosed AML (7/28) and 19% of patients with R/R AML (34/179) experienced differentiation syndrome
    • Onset occurred as early as 1 day and up to 3 months after initiation of TIBSOVO 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
    • Of those who experienced differentiation syndrome, 86% of patients with newly diagnosed AML (6/7) and 79% of patients with R/R AML (27/34) recovered after treatment or after dose interruption of TIBSOVO
  • If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) 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
  • Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment
Chart Icon - Noninfectious leukocytosis

Noninfectious leukocytosis1

  • 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 prolongation1

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 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
Chart Icon - Guillain-Barre syndrome

Guillain-Barré syndrome1

  • <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
Chart Icon - Other ≥ Grade 3 toxicity considered related to treatment

Other Grade ≥3 toxicity considered related to treatment1,a

  • 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
IV, intravenous.

a Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe.

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Drug-drug interactions

Drug-drug interactions with TIBSOVO1

Strong or moderate CYP3A4 inhibitors1

  • 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 inducers1

  • Coadministration decreased ivosidenib plasma concentrations
  • Avoid coadministration

QTc-prolonging drugs1

  • 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 drugs1

  • 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
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Learn how TIBSOVO works

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2021. 2. Data on file. Servier Pharmaceuticals LLC.

 
 

Indications

TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA-approved test with:

  • Adult patients with newly-diagnosed Acute Myeloid Leukemia (AML) who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
  • Adult patients with relapsed or refractory AML.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN AML
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.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome in AML: In the clinical trial, 25% (7/28) of patients with newly diagnosed AML and 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms of differentiation syndrome in patients treated with TIBSOVO 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. Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. Of the 34 patients with relapsed or refractory AML who experienced differentiation syndrome, 27 (79%) patients recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.

QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. One patient developed ventricular fibrillation attributed to TIBSOVO. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (e.g., anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.

Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

Guillain-Barré Syndrome: Guillain-Barré syndrome can develop in patients treated with TIBSOVO. Monitor patients taking TIBSOVO 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. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

ADVERSE REACTIONS

  • In patients with AML, the most common adverse reactions including laboratory abnormalities (≥20%) were hemoglobin decreased (60%), fatigue (43%), arthralgia (39%), calcium decreased (39%), sodium decreased (39%), leukocytosis (38%), diarrhea (37%), magnesium decreased (36%), edema (34%), nausea (33%), dyspnea (32%), uric acid increased (32%), potassium decreased (32%), alkaline phosphatase increased (30%), mucositis (28%), aspartate aminotransferase increased (27%), phosphatase decreased (25%), electrocardiogram QT prolonged (24%), rash (24%), creatinine increased (24%), cough (23%), decreased appetite (22%), myalgia (21%), constipation (20%), and pyrexia (20%).
  • In patients with newly diagnosed AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were fatigue (14%), differentiation syndrome (11%), electrocardiogram QT prolonged (11%), diarrhea (7%), nausea (7%), and leukocytosis (7%). Serious adverse reactions (≥5%) were differentiation syndrome (18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There was one case of posterior reversible encephalopathy syndrome (PRES).
  • In patients with relapsed or refractory AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were differentiation syndrome (13%), electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), and tumor lysis syndrome (6%). Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).

DRUG INTERACTIONS

Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.

Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.

Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.

QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.

LACTATION

Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for at least 1 month after the last dose.

Please see Full Prescribing Information, including BOXED WARNING for AML patients.

 

INDICATIONS

TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA-approved test with:

  • Adult patients with newly-diagnosed Acute Myeloid Leukemia (AML) who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
  • Adult patients with relapsed or refractory AML.
Indications & Important Safety Information

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN AML

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.

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