TIBSOVO

) 2 CONTRAINDICATIONS TIBSOVO is contraindicated in patients: • who are hypersensitive to this drug or to any ingredient in the formulation, including any non- medicinal ingredient, or component of the container. For a complete listing, (see

). 1 Dosing Considerations • Treatment should be initiated under the supervision of a health professional experienced in the use of anti-cancer medicinal products. • Before taking TIBSOVO, patients must have confirmation of an IDH1 R132 mutation using an appropriate diagnostic test.

• An electrocardiogram (ECG) must be performed prior to treatment initiation. Heart rate corrected QT (QTc) should be less than 450 msec prior to treatment initiation and, in the presence of an abnormal QT, the benefit/risk of initiating TIBSOVO should be reassessed.

In case QTc interval prolongation is between 480 msec and 500 msec, initiation of treatment with TIBSOVO should remain exceptional and be accompanied by close monitoring. • An ECG must be performed prior to treatment initiation, at least weekly during the first 3 weeks of therapy and then at least monthly for the duration of therapy.

Any abnormalities should be managed promptly (see Table 1 and 7 WARNINGS AND PRECAUTIONS). • If a moderate or strong CYP3A4 inhibitor cannot be avoided, the dose of TIBSOVO should be reduced to 250 mg once daily. If the moderate or strong inhibitor is discontinued, the dose of TIBSOVO should be increased (after at least 5 half-lives of the CYP3A4 inhibitor) to the recommended dose of 500 mg once daily (see

). • QTc interval prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. Monitor electrocardiograms and electrolytes. If QTc interval prolongation occurs, dose reduce or interrupt, then resume dose or permanently discontinue TIBSOVO (see 4 DOSAGE AND ADMINISTRATION; 7 WARNINGS AND PRECAUTIONS;

TIBSOVO is contraindicated in patients: • who are hypersensitive to this drug or to any ingredient in the formulation, including any non- medicinal ingredient, or component of the container. For a complete listing, (see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING) • are taking strong CYP3A4 inducers or dabigatran.

• with congenital long QT syndrome. • with a family history of sudden death or polymorphic ventricular arrythmia. • with a QT/QTc interval > 500 msec, regardless of the correction method used. TIBSOVO (ivosidenib) Page 5 of 40