Source: FDA, National Drug Code (US) Revision Year: 2020
TIBSOVO 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 [see Dosage and Administration (2.1), Clinical Pharmacology (12.1) and Clinical Studies (14.1)].
TIBSOVO 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 [see Dosage and Administration (2.1), Clinical Pharmacology (12.1) and Clinical Studies (14.2)].
Select patients for the treatment of AML with TIBSOVO based on the presence of IDH1 mutations in the blood or bone marrow [see Clinical Studies (14.1)]. Patients without IDH1 mutations at diagnosis should be retested at relapse because a mutation in IDH1 may emerge during treatment and at relapse. Information on FDA-approved tests for the detection of IDH1 mutations in AML is available at http://www.fda.gov/CompanionDiagnostics.
The recommended dose of TIBSOVO is 500 mg taken orally once daily until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response.
Administer TIBSOVO with or without food. Do not administer TIBSOVO with a high-fat meal because of an increase in ivosidenib concentration [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. Do not split or crush TIBSOVO tablets. Administer TIBSOVO tablets orally about the same time each day. If a dose of TIBSOVO is vomited, do not administer a replacement dose; wait until the next scheduled dose is due. If a dose of TIBSOVO 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.
Treatment with TIBSOVO 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 TIBSOVO [see Use in Specific Populations (8.6, 8.7)].
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 electrocardiograms (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 [see Adverse Reactions (6.1)].
Interrupt dosing or reduce dose for toxicities. See Table 1 for dose modification guidelines.
Table 1. Recommended Dose Modifications for TIBSOVO:
| Adverse Reactions | Recommended Action |
|---|---|
| • Differentiation syndrome | • If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days [see Warnings and Precautions (5.1)]. • Interrupt TIBSOVO if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids [see Warnings and Precautions (5.1)] • Resume TIBSOVO when signs and symptoms improve to Grade 2* or lower. |
| • Noninfectious leukocytosis (white blood cell [WBC] count greater than 25 × 109/L or an absolute increase in total WBC of greater than 15 × 109/L from baseline) | • 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. |
| • QTc interval greater than 480 msec to 500 msec | • Monitor and supplement electrolyte levels as clinically indicated [see Warnings and Precautions (5.2)]. • Review and adjust concomitant medications with known QTc interval-prolonging effects [see Drug Interactions (7.1)]. • Interrupt TIBSOVO • Restart TIBSOVO at 500 mg once daily after the QTc interval returns to less than or equal to 480 msec. • Monitor ECGs at least weekly for 2 weeks following resolution of QTc prolongation. |
| • QTc interval greater than 500 msec | • Monitor and supplement electrolyte levels as clinically indicated [see Warnings and Precautions (5.2)]. • Review and adjust concomitant medications with known QTc interval-prolonging effects [see Drug Interactions (7.1)] • Interrupt TIBSOVO • Resume TIBSOVO at a reduced dose of 250 mg once daily when QTc interval returns to within 30 msec of baseline or less than or equal to 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 [see Warnings and Precautions (5.2)]. |
| • Guillain-Barré syndrome | • Discontinue TIBSOVO permanently [see Warnings and Precautions (5.3)]. |
| • Other Grade 3* or higher toxicity considered related to treatment | • Interrupt TIBSOVO until toxicity resolves to Grade 2* or lower. • Resume TIBSOVO at 250 mg once daily; may increase to 500 mg once daily if toxicities resolve to Grade 1* or lower. • If Grade 3* or higher toxicity recurs, discontinue TIBSOVO. |
* Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening.
If a strong CYP3A4 inhibitor must be coadministered, reduce the TIBSOVO dose 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.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
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