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Now approved FOR PATIENTS WITH R/R MDS

TIBSOVO® is indicated for the treatment of adult patients with relapsed or refractory myelodysplastic syndromes (R/R MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

Press Release Prescribing Information
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IDH1 mutations can play a critical role in the development of AML1-4

IDH1 mutations block normal differentiation of myeloblasts1-3

idh1-diagram-desktop Chart idh1-diagram-mobile Chart

IDH1 mutations are driver mutations that occur in up to 14% of patients with AML2,4

  • mIDH1 contributes to oncogenesis by catalyzing the production of 2-HG, which leads to disruption of cellular metabolism and epigenetic regulation5
  • Several studies have suggested that mIDH1 AML is associated with a poor prognosis5,6

2-HG, D-2-hydroxyglutarate; AML, acute myeloid leukemia; IDH1, isocitrate dehydrogenase‑1.

Test for IDH1 mutations at diagnosis and relapse so you can offer targeted therapy to appropriate patients7,8

  • Both the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) and ASH‑CAP Guidelines recommend testing for IDH1 mutations in patients with AML7,8
    • "To appropriately stratify available intensive therapy options, expedite test results of molecular and cytogenetic analyses for immediately actionable mutations or chromosomal abnormalities (eg, core binding factor [CBF], FLT3 [ITD and TKD], NPM1, IDH1, IDH2)”
      - National Comprehensive Cancer Network® (NCCN®)8
  • Patients without IDH1 mutations at diagnosis should be retested at relapse because a mutation in IDH1 may emerge during treatment and at relapse9
  • In the pivotal trials, IDH1 mutations were identified by a local or central diagnostic test and confirmed retrospectively using the Abbott RealTime IDH1 assay, which is the FDA-approved test for selection of patients with AML for treatment with TIBSOVO9
  • NCCN Guidelines® recommends ivosidenib (TIBSOVO) + azacitidine as a category 1 preferred treatment option for newly diagnosed patients with mIDH1 who are not candidates for intensive remission induction therapy8
  • NCCN Guidelines recommends ivosidenib (TIBSOVO) monotherapy for IC-ineligible, newly diagnosed and R/R AML patients with an IDH1 mutation8

AML, acute myeloid leukemia; ASH, American Society of Hematology; CAP, College of American Pathologists; IC, induction chemotherapy; IDH1, isocitrate dehydrogenase‑1; R/R, relapsed/refractory.

TIBSOVO (ivosidenib tablets) targets the mutant IDH1 enzyme to restore myeloid differentiation1,9

TIBSOVO restores differentiation of myeloblasts1,9

idh1-diagram-2-desktop Chart idh1-diagram-2-mobile Chart
  • In blood samples from patients with AML with mutated IDH1, ivosidenib decreased 2-HG levels ex vivo, reduced blast counts, and increased percentages of mature myeloid cells9
  • Ivosidenib was shown to inhibit selected IDH1 R132 mutants at much lower concentrations than wild-type IDH1 in vitro9
  • Susceptible IDH1 mutations are defined as those leading to increased levels of 2-HG in the leukemia cells and where efficacy is predicted by (1) clinically meaningful remissions with the recommended dose of ivosidenib and/or (2) inhibition of mutant IDH1 enzymatic activity at concentrations of ivosidenib sustainable at the recommended dosage according to validated methods9
    • Susceptible IDH1 mutations are R132C, R132G, R132H, R132L, and R132S9

2-HG, D-2-hydroxyglutarate; AML, acute myeloid leukemia; IDH1, isocitrate dehydrogenase‑1.

See TIBSOVO access and resources

References: 1. Data on file. Servier Pharmaceuticals LLC. 2. Molenaar RJ, Maciejewski JP, Wilmink JW, van Noorden CJF. Wild-type and mutated IDH1/2 enzymes and therapy responses. Oncogene. 2018;37(15):1949-1960. 3. Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553-567. 4. Megías-Vericat JE, Ballesta-López O, Barragán E, Montesinos P. IDH1-mutated relapsed or refractory AML: current challenges and future prospects. Blood Lymphat Cancer. 2019;9:19-32. doi:10.2147/BLCTT.S177913 5. Roboz GJ, DiNardo CD, Stein EM, et al. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood. 2020;135(7):463-471. 6. Xu Q, Li Y, Lv N, et al. Correlation between isocitrate dehydrogenase gene aberrations and prognosis of patients with acute myeloid leukemia: a systemic review and meta-analysis. Clin Cancer Res. 2017;23(15):4511-4522. 7. Arber DA, Borowitz MJ, Cessna M, et al. Initial diagnostic workup of acute leukemia: Guideline from the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017;141(10):1342-1393. 8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2022. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed March 2, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. 9. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2022.

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Indications

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

Newly Diagnosed Acute Myeloid Leukemia (AML)

  • In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy

Relapsed or Refractory AML

  • For the treatment of adult patients with relapsed or refractory AML

Relapsed or Refractory Myelodysplastic Syndromes (MDS)

  • For the treatment of adult patients with relapsed or refractory MDS

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN AML AND MDS
Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal. 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 and MDS: Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. 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.

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. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (eg, 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, electrolyte abnormalities, or 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 (≥25%) are leukocytes decreased, diarrhea, hemoglobin decreased, platelets decreased, glucose increased, fatigue, alkaline phosphatase increased, edema, potassium decreased, nausea, vomiting, phosphate decreased, decreased appetite, sodium decreased, leukocytosis, magnesium decreased, aspartate aminotransferase increased, arthralgia, dyspnea, uric acid increased, abdominal pain, creatinine increased, mucositis, rash, electrocardiogram QT prolonged, differentiation syndrome, calcium decreased, neutrophils decreased, and myalgia
  • In patients with MDS, the most common adverse reactions including laboratory abnormalities (≥25%) are creatinine increased, hemoglobin decreased, arthralgia, albumin decreased, aspartate aminotransferase increased, fatigue, diarrhea, cough, sodium decreased, mucositis, decreased appetite, myalgia, phosphate decreased, pruritus, and rash

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

Advise women not to breastfeed.

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

 

INDICATIONS

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

Newly Diagnosed Acute Myeloid Leukemia (AML)

  • In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude the use of intensive induction chemotherapy
Indications & Important Safety Information

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN AML AND MDS

Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal. 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.