Ivosenib

Newly-Diagnosed Acute Myeloid Leukemia
: Ivosenib is indicated for the treatment of newly-diagnosed acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA approved test in adult patients who are ≥ 75 years old or who have
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Newly-Diagnosed Acute Myeloid Leukemia
: Ivosenib is indicated for the treatment of newly-diagnosed acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA approved test in adult patients who are ≥ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
Relapsed or Refractory Acute Myeloid Leukemia
: Ivosenib 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.
Locally Advanced or Metastatic Cholangiocarcinoma
: Ivosenib is indicated for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

Dosage & Administration

Acute Myeloid Leukemia
: Select patients for the treatment of AML with Ivosidenib based on the presence of IDH1 mutations in the blood or bone marrow. Patients with AML without IDH1 mutations at diagnosis should be retested at relapse because a mutation in IDH1 may emerge during treatment and at relapse.
Locally Advanced or Metastatic Cholangiocarcinoma
: Select patients for the treatment of locally advanced or metastatic cholangiocarcinoma with Ivosidenib based on the presence of IDH1 mutations.
Recommended Dosage
: The recommended dose of Ivosidenib is 500 mg taken orally once daily until disease progression or unacceptable toxicity. Administer Ivosidenib with or without food. Do not administer Ivosidenib with a high-fat meal because of an increase in Ivosidenib. Do not split or crush Ivosidenib tablets. Administer Ivosidenib tablets orally about the same time each day. If a dose of Ivosidenib is vomited, do not administer a replacement dose; wait until the next scheduled dose is due. If a dose of Ivosidenib is missed or not taken at the usual time, administer the dose as soon as possible and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer 2 doses within 12 hours.
Patients with Acute Myeloid Leukemia
: For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response.
Patients with the Comorbidities of Severe Renal or Severe Hepatic Impairment
: Treatment with Ivosidenib has not been studied in patients with pre-existing severe renal or hepatic impairment. For patients with pre-existing severe renal or hepatic impairment, consider the risks and potential benefits before initiating treatment with Ivosidenib.

The following adverse reactions are discussed in greater detail in other sections of the labeling:
Differentiation Syndrome in AML
QTc Interval Prolongation
Guillain-Barré Syndrome
Fever
Cough
Trouble Breathing
Rash
Decreased Urination
Dizziness or Lightheadedness
Rapid Weight Gain
Swelling of Your Arms or Legs

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 Ivosenib 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 Ivosenib included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumorlysis 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 Ivosenib. Differentiation syndrome occurred as early as 1 day and up to 3 months after Ivosenib initiation and has been observed with or without concomitant leukocytosis.
QTc Interval Prolongation
: Patients treated with Ivosenib can develop QT (QTc) prolongation and ventricular arrhythmias. Of the 258 patients with hematological malignancies treated with Ivosenib in the clinical trial (AG120-C-001), 9% were found to have a QTc interval greater than 500 msec and 14% of patients had an increase from baseline QTc greater than 60 msec. One patient developed ventricular fibrillation attributed to Ivosenib. The clinical trial excluded patients with baseline QTc of ≥ 450 msec (unless the QTc ≥ 450 msec was due to a pre-existing bundle branch block) or with a history of long QT syndrome or uncontrolled or significant cardiovascular disease.
Guillain-Barré Syndrome
: Guillain-Barré syndrome can develop in patients treated with Ivosenib. Guillain-Barré syndrome occurred in <1% (2/258) of patients treated with Ivosenib in study AG120-C-001. Monitor patients taking Ivosenib 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 Ivosenib in patients who are diagnosed with Guillain-Barré syndrome.