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TIBSOVO (ivosidenib tablets) has a well-characterized safety profile studied in more than 270 patients with mIDH1 AML1
COMBINATION THERAPY

TIBSOVO in combination with azacitidine for treatment of newly diagnosed IC-ineligible mIDH1 AML

Adverse reactions

Adverse reactions (≥10%) in patients with AML who received TIBSOVO + azacitidine with a difference of ≥2% between arms compared with placebo + azacitidine1
TIBSOVO + azacitidine
(N=71) 		Placebo + azacitidine
(N=73)
Body system
Adverse reaction 		All grades Grade ≥3 All grades Grade ≥3
Gastrointestinal disorders
Nausea 42% 3% 38% 4%
Vomiting 41% 0 27% 1%
Investigations
Electrocardiogram QT prolonged 20% 10% 7% 3%
Psychiatric disorders
Insomnia 18% 1% 12% 0
Blood system and lymphatic system disorders
Differentiation
syndromea 		15% 10% 8% 8%
Leukocytosis 13% 0 1% 0
Vascular disorders
Hematoma 15% 0 4% 0
Hypertension 13% 4% 8% 5%
Musculoskeletal and connective tissue disorder
Arthralgia 30% 4% 8% 1%
Respiratory, thoracic, and mediastinal disorders
Dyspnea 20% 3% 15% 5%
Nervous system disorders
Headache 11% 0% 3% 0%
Adverse reactions (≥10%) in patients with AML who received TIBSOVO + azacitidine with a difference of ≥2% between arms compared with placebo + azacitidine
  TIBSOVO + azacitidine
(N=71)
Body system
Adverse reaction 		All grades Grade ≥3
Gastrointestinal disorders
Nausea 42% 3%
Vomiting 41% 0
Investigations
Electrocardiogram QT prolonged 20% 10%
Psychiatric disorders
Insomnia 18% 1%
Blood system and lymphatic system disorders
Differentiation
syndromea 		15% 10%
Leukocytosis 13% 0
Vascular disorders
Hematoma 15% 0
Hypertension 13% 4%
Musculoskeletal and connective tissue disorders
Arthralgia 30% 4%
Respiratory, thoracic, and mediastinal disorders
Dyspnea 20% 3%
Nervous system disorders
Headache 11% 0
  Placebo + azacitidine
(N=73)
Body system
Adverse reaction 		All grades Grade ≥3
Gastrointestinal disorders
Nausea 38% 4%
Vomiting 27% 1%
Investigations
Electrocardiogram QT prolonged 7% 3%
Psychiatric disorders
Insomnia 12% 0
Blood system and lymphatic system disorders
Differentiation
syndromea 		8% 8%
Leukocytosis 1% 0
Vascular disorders
Hematoma 4% 0
Hypertension 8% 5%
Musculoskeletal and connective tissue disorders
Arthralgia 8% 1%
Respiratory, thoracic, and mediastinal disorders
Dyspnea 15% 5%
Nervous system disorders
Headache 3% 0

IC, induction chemotherapy; mIDH1, mutated isocitrate dehydrogenase-1.

a Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening.

b Differentiation syndrome can be associated with other commonly reported events such as peripheral edema, leukocytosis, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonia, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased.

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  • TIBSOVO + azacitidine was associated with a lower rate of infection of any grade compared with azacitidine (28% vs 49%)2

Select laboratory abnormalities

Select laboratory abnormalities (≥10%) that worsened from baseline in patients with newly diagnosed AML who received TIBSOVO + azacitidine1,a,b
TIBSOVO + azacitidine
(N=71) 		Placebo + azacitidine
(N=73)
Parameter All grades Grade ≥3 All grades Grade ≥3
Hematology parameters
Leukocytes decreased 65% 55% 64% 58%
Platelets decreased 58% 42% 71% 58%
Hemoglobin decreased 56% 46% 66% 58%
Neutrophils decreased 25% 23% 35% 32%
Lymphocytes increased 24% 1% 10% 1%
Chemistry parameters
Glucose increased 56% 13% 47% 11%
Phosphate decreased 41% 10% 34% 12%
Aspartate aminotransferase increased 37% 0 23% 0
Magnesium decreased 35% 0 26% 0
Alkaline phosphatase increased 32% 0 29% 0
Potassium increased 24% 3% 12% 1%
Select laboratory abnormalities (≥10%) that worsened from baseline in patients with newly diagnosed AML who received TIBSOVO + azacitidinea,b
  TIBSOVO + azacitidine
(N=71)
Paramater All grades Grade ≥3
Hematology parameters
Leukocytes decreased 65% 55%
Platelets decreased 58% 42%
Hemoglobin decreased 56% 46%
Neutrophils decreased 25% 23%
Lymphocytes decreased 24% 1%
Chemistry parameters
Glucose increased 56% 13%
Phosphate decreased 41% 10%
Aspartate aminotransferase increased 37% 0
Magnesium decreased 35% 0
Alkaline phosphatase increased 32% 0
Potassium increased 24% 3%
  Placebo + azacitidine
(N=73)
Paramater All grades Grade ≥3
Hematology parameters
Leukocytes decreased 64% 58%
Platelets decreased 71% 58%
Hemoglobin decreased 66% 58%
Neutrophils decreased 35% 32%
Lymphocytes increased 10% 1%
Chemistry parameters
Glucose increased 47% 11%
Phosphate decreased 34% 12%
Aspartate aminotransferase increased 23% 0
Magnesium decreased 26% 0
Alkaline phosphatase increased 29% 0
Potassium increased 12% 1%

aLaboratory abnormality was defined as new or worsened by at least one grade from baseline or if baseline was unknown.

bThe denominator used to calculate percentages is the number of treated subjects who can be evaluated for Common Terminology for Adverse Events (CTCAE) criteria for each parameter in each arm.

  • TIBSOVO + azacitidine was associated with fewer severe cytopenias compared with azacitidine1,2
  • Median duration of exposure to TIBSOVO was 6 months (range, 0 to 33)1
    • 34 patients (48%) were exposed to TIBSOVO for at least 6 months
    • 22 patients (31%) were exposed to TIBSOVO for at least 1 year
  • Fatal adverse reactions occurred in 4% of patients due to differentiation syndrome (3%) and one case of cerebral ischemia1

TIBSOVO + azacitidine: Dose discontinuations, interruptions, and reductions1

  TIBSOVO + azacitidine for newly diagnosed AML (N=71)
Adverse reactions that lead to permanent discontinuation in ≥2% of patients Differentiation syndrome (3%), pulmonary embolism (3%)
Most common (>5%) adverse reactions that lead to dose interruption Neutropenia (25%), electrocardiogram QT prolonged (7%), thrombocytopenia (7%)
Adverse reactions that lead to dose reduction Electrocardiogram QT prolonged (8%), neutropenia (8%), thrombocytopenia (1%)
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MONOTHERAPY

Safety profile: TIBSOVO monotherapy

Adverse reactions common to both the newly diagnosed and R/R settings
reported in ≥10% (any grade) or ≥5% (Grade ≥3) of patients who received TIBSOVO monotherapy1
Newly diagnosed AML
(N=28) 		R/R AML
(N=179)
Body system
Adverse reaction 		All grades Grade ≥3 All grades Grade ≥3
Gastrointestinal disorders
Diarrhea 61% 7% 34% 2%
Nausea 36% 7% 31% 1%
Abdominal pain 29% 4% 16% 1%
Constipation 21% 4% 20% 1%
Vomiting 21% 4% 18% 1%
Mucositis 21% 0% 28% 3%
General disorders and administration site conditions
Fatigue 50% 14% 39% 3%
Edema 43% 0% 32% 1%
Metabolism and nutrition disorders
Decreased appetite 39% 4% 18% 2%
Blood system and lymphatic system disorders
Leukocytosis 36% 7% 38% 8%
Differentiation
syndromea 		25% 11% 19% 13%
Musculoskeletal and connective tissue disorders
Arthralgia 32% 4% 36% 4%
Myalgia 25% 4% 18% 1%
Respiratory, thoracic, and mediastinal disorders
Dyspnea 29% 4% 33% 9%
Cough 14% 0% 22% <1%
Investigations
Electrocardiogram QT prolonged 21% 11% 26% 10%
Nervous system disorders
Neuropathy 14% 0% 12% 1%
Headache 11% 0% 16% 0%
Skin and subcutaneous tissue disorders
Rash 14% 4% 26% 2%
Adverse reactions common to both the newly diagnosed and R/R settings
reported in ≥10% (any grade) or ≥5% (Grade ≥3) of patients who received TIBSOVO monotherapy1
  Newly diagnosed AML
(N=28)
Body system
Adverse reaction 		All grades Grade ≥3
Gastrointestinal disorders
Diarrhea 61% 7%
Nausea 36% 7%
Abdominal pain 29% 4%
Constipation 21% 4%
Vomiting 21% 4%
Mucositis 21% 0%
General disorders and administration site conditions
Fatigue 50% 14%
Edema 43% 0%
Metabolism and nutrition disorders
Decreased appetite 39% 4%
Blood system and lymphatic system disorders
Leukocytosis 36% 7%
Differentiation
syndromea 		25% 11%
Musculoskeletal and connective tissue disorders
Arthralgia 32% 4%
Myalgia 25% 4%
Respiratory, thoracic, and mediastinal disorders
Dyspnea 29% 4%
Cough 14% 0%
Investigations
Electrocardiogram QT prolonged 21% 11%
Nervous system disorders
Neuropathy 14% 0%
Headache 11% 0%
Skin and subcutaneous tissue disorders
Rash 14% 4%
  R/R AML
(N=179)
Body system
Adverse reaction 		All grades Grade ≥3
Gastrointestinal disorders
Diarrhea 34% 2%
Nausea 31% 1%
Abdominal pain 16% 1%
Constipation 20% 1%
Vomiting 18% 1%
Mucositis 28% 3%
General disorders and administration site conditions
Fatigue 39% 3%
Edema 32% 1%
Metabolism and nutrition disorders
Decreased appetite 18% 2%
Blood system and lymphatic system disorders
Leukocytosis 38% 8%
Differentiation
syndromea 		19% 13%
Musculoskeletal and connective tissue disorders
Arthralgia 36% 4%
Myalgia 18% 1%
Respiratory, thoracic, and mediastinal disorders
Dyspnea 33% 9%
Cough 22% <1%
Investigations
Electrocardiogram QT prolonged 26% 10%
Nervous system disorders
Neuropathy 12% 1%
Headache 16% 0%
Skin and subcutaneous tissue disorders
Rash 26% 2%

R/R, relapsed or refractory.

aDifferentiation syndrome can be associated with other commonly reported events such as peripheral edema, leukocytosis, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonia, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased.1

Additional adverse reactions in the newly diagnosed monotherapy setting

Additional adverse reactions in the newly diagnosed setting reported in ≥10% (any grade) or ≥5% (Grade ≥3) of patients who received TIBSOVO monotherapy1
  Newly diagnosed AML
(N=28)
Adverse reaction All grades Grade ≥3
Dizziness 21% 0%
Pruritus 14% 4%
Dyspepsia 11% 0%
Weight decreased 11% 0%
  • Common (≥5%) serious adverse events included differentiation syndrome (18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There was one case of posterior reversible encephalopathy syndrome (PRES)1
  • Median duration of exposure to TIBSOVO: 4.3 months (range, 0.3-40.9)1
    • 10 patients (36%) were exposed to TIBSOVO for ≥6 months and 6 patients (21%) for ≥1 year

Additional adverse reactions in the R/R monotherapy setting

Additional adverse reactions in the R/R setting reported in ≥10% (any grade) or ≥5% (Grade ≥3) of patients who received TIBSOVO monotherapy1
  R/R AML
(N=179)
Adverse reaction All grades Grade ≥3
Pyrexia 23% 1%
Chest pain 16% 3%
Pleural effusion 13% 3%
Hypotension 12% 4%
Tumor lysis syndrome 8% 6%

R/R, relapsed or refractory.

  • Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML)1
  • Median duration of exposure to TIBSOVO: 3.9 months (range, 0.1-39.5)1
    • 65 patients (36%) were exposed to TIBSOVO for ≥6 months and 16 patients (9%) for ≥1 year

Laboratory abnormalities reported in patients who received TIBSOVO monotherapy1

Laboratory abnormalities common to both the newly diagnosed and R/R settings reported in ≥10% (any grade) or ≥5% (Grade ≥3) of patients who received TIBSOVO monotherapy1,b
  Newly diagnosed AML
(N=28) 		R/R AML
(N=179)
Parameter All grades Grade ≥3 All grades Grade ≥3
Hemoglobin decreased 54% 43% 60% 46%
Alkaline phosphatase increased 46% 0% 27% 1%
Potassium decreased 43% 11% 31% 6%
Sodium decreased 39% 4% 39% 4%
Uric acid increased 29% 4% 32% 6%
Aspartate aminotransferase increased 29% 4% 27% 1%
Creatinine increased 29% 0% 23% 1%
Magnesium decreased 25% 0% 38% 0%
Phosphate decreased 21% 7% 25% 8%
Alanine aminotransferase increased 14% 4% 15% 1%
Laboratory abnormalities common to both the newly diagnosed and R/R settings reported in ≥10% (any grade) or ≥5% (Grade ≥3) of patients who received TIBSOVO monotherapy1,b
  Newly diagnosed AML
(N=28)
Parameter All grades Grade ≥3
Hemoglobin decreased 54% 43%
Alkaline phosphatase increased 46% 0%
Potassium decreased 43% 11%
Sodium decreased 39% 4%
Uric acid increased 29% 4%
Aspartate aminotransferase increased 29% 4%
Creatinine increased 29% 0%
Magnesium decreased 25% 0%
Phosphate decreased 21% 7%
Alanine aminotransferase increased 14% 4%
  R/R AML
(N=179)
Parameter All grades Grade ≥3
Hemoglobin decreased 60% 46%
Alkaline phosphatase increased 27% 1%
Potassium decreased 31% 6%
Sodium decreased 39% 4%
Uric acid increased 32% 6%
Aspartate aminotransferase increased 27% 1%
Creatinine increased 23% 1%
Magnesium decreased 38% 0%
Phosphate decreased 25% 8%
Alanine aminotransferase increased 15% 1%

R/R, relapsed or refractory.

bLaboratory abnormality was defined as new or worsened by at least one grade from baseline or if baseline is unknown.1

Additional laboratory abnormalities reported in ≥10% (any grade) or ≥5% (Grade ≥3) of patients1:

  • In patients with newly diagnosed AML: calcium decreased (all grades, 25%; Grade ≥3, 4%)
  • In patients with R/R AML: bilirubin increased (all grades, 16%; Grade ≥3, 1%)

Monotherapy: Dose discontinuations, interruptions, and reductions1

Newly diagnosed AML (N=28) R/R AML (N=179)
Adverse reactions that led to permanent discontinuation Diarrhea (4%), PRES (4%) Guillain-Barré syndrome (1%), rash (1%), stomatitis (1%), creatinine increased (1%)
Most common adverse reactions that led to dose interruption Electrocardiogram QT prolonged (14%), differentiation syndrome (11%) Electrocardiogram QT prolonged (7%), differentiation syndrome (3%), leukocytosis (3%), dyspnea (3%)
Adverse reactions that led to dose reduction Electrocardiogram QT prolonged (7%) 3% of patients required a dose reduction due to an adverse reaction

- Adverse reactions leading to dose reduction included electrocardiogram QT prolonged (1%), diarrhea (1%), nausea (1%), decreased hemoglobin (1%), increased transaminases (1%)
Newly diagnosed AML
(N=28)
Adverse reactions that led to permanent discontinuation Diarrhea (4%), PRES (4%)
Most common adverse reactions that led to dose interruption Electrocardiogram QT prolonged (14%), differentiation syndrome (11%)
Adverse reactions that led to dose reduction Electrocardiogram QT prolonged (7%)
R/R AML
(N=179)
Adverse reactions that led to permanent discontinuation Guillain-Barré syndrome (1%), rash (1%), stomatitis (1%), creatinine increased (1%)
Most common adverse reactions that led to dose interruption Electrocardiogram QT prolonged (7%), differentiation syndrome (3%), leukocytosis (3%), dyspnea (3%)
Adverse reactions that led to dose reduction 3% of patients required a dose reduction due to an adverse reaction
  • Adverse reactions leading to dose reduction included electrocardiogram QT prolonged (1%), diarrhea (1%), nausea (1%), decreased hemoglobin (1%), increased transaminases (1%)

PRES, posterior reversible encephalopathy syndrome.

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TIBSOVO monotherapy was associated with a low rate of severe cytopenias3,4

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 (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, 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.

Learn about TIBSOVO dosing

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2022. 2. Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med. 2022;386(16):1519-1531. doi:10.1056/NEJMoa2117344 3. 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. doi:10.1182/blood.2019002140 4. DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378(25):2386-2398. doi:10.1056/NEJMoa1716984

 
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Indications

TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible 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

Relapsed or Refractory AML

  • For the treatment of 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. 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 combination study AG120-C-009, 15% (11/71) of patients with newly diagnosed AML treated with TIBSOVO plus azacitidine experienced differentiation syndrome. 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. Of the 11 patients with newly diagnosed AML who experienced differentiation syndrome with TIBSOVO plus azacitidine, 8 (73%) recovered. Differentiation syndrome occurred as early as 3 days after start of therapy and during the first month on treatment.

In the monotherapy clinical trial AG120-C-001, 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. 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. 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, 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 (≥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

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 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 patients with a susceptible 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
  • 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. 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.