JAKAVI

3 Pediatrics 05/2022 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ...........................................................................................

2 TABLE OF CONTENTS ............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION ......................................................................

4 1 INDICATIONS ................................................................................................... 4 2 CONTRAINDICATIONS ...................................................................................... 5 3 SERIOUS WARNINGS AND PRECAUTIONS BOX .................................................

5 4 DOSAGE AND ADMINISTRATION ...................................................................... 12 5 OVERDOSAGE ................................................................................................ 12

). 2 Recommended Dose and Dosage Adjustment Myelofibrosis and Polycythemia Vera JAKAVI® ruxolitinib (as ruxolitinib phosphate) Page 6 of 77 The recommended starting dose of JAKAVI in MF and PV is based on platelet count (Table 1). A complete blood count and platelet count must be performed before initiating therapy, every 2 to 4 weeks until doses are stabilized, and then as clinically indicated.

Table 1 JAKAVI starting doses for patients with MF or PV Platelet Count Starting Dose Myelofibrosis Polycythemia vera Greater than 200,000/mm3 20 mg orally twice daily 10 mg orally twice daily 100,000 to 200,000/mm3 15 mg orally twice daily 10 mg orally twice daily 75,000 to <100,000/mm3 10 mg orally twice daily 5 mg orally twice daily 50,000 to <75,000/mm3 5 mg orally twice daily 5 mg orally twice daily Prior to initiating treatment with JAKAVI, the Absolute Neutrophil Count (ANC) of patients should be >1000/mm3.

Dose modifications based on safety Treatment interruptions:

Treatment with JAKAVI should be interrupted if: • platelet counts less than 50,000/mm3. • absolute neutrophil counts less than 500/mm3. • hemoglobin less than 8g/dL (only for PV patients). After recovery of cell blood counts above these levels, dosing may be restarted at 5 mg twice daily and gradually increased based on careful monitoring of blood cell counts.

Interrupt treatment for bleeding requiring intervention regardless of current platelet count. Once the bleeding event has resolved, consider resuming treatment at the prior dose if the underlying cause of bleeding has been controlled.

If the bleeding event has resolved but the underlying cause persists, consider resuming treatment with JAKAVI at a lower dose.

Dose reductions:

Dose reductions in MF should be considered if the platelet counts decrease as outlined in Table 2, with the goal of avoiding dose interruptions for thrombocytopenia. Table 2 Dosing recommendations for thrombocytopenia in MF Platelet Count Dose at Time of Platelet Decline 25 mg twice daily 20 mg twice daily 15 mg twice daily 10 mg twice daily 5 mg twice daily New Dose New Dose New Dose New Dose New Dose 100,000 to less than 125,000/mm3 20 mg twice daily 15 mg twice daily No Change No Change No Change 75,000 to less than 100,000/mm3 10 mg twice daily 10 mg twice daily 10 mg twice daily No Change No Change 50,000 to less than 75,000/mm3 5 mg twice daily 5 mg twice daily 5 mg twice daily 5 mg twice daily No Change JAKAVI® ruxolitinib (as ruxolitinib phosphate) Page 7 of 77 Less than 50,000/mm3 Hold Hold Hold Hold Hold For PV patients, dose reduction should also be considered if hemoglobin decreases below 12g/dL and is recommended if hemoglobin decreases below 10g/dL.

3 Pediatrics 05/2022 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ...........................................................................................

2 TABLE OF CONTENTS ............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION ......................................................................

4 1 INDICATIONS ................................................................................................... 4 2 CONTRAINDICATIONS ...................................................................................... 5 3 SERIOUS WARNINGS AND PRECAUTIONS BOX .................................................

5 4 DOSAGE AND ADMINISTRATION ...................................................................... 12 5 OVERDOSAGE ................................................................................................ 12 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING....................

12 7 WARNINGS AND PRECAUTIONS ..................................................................... 19 8 ADVERSE REACTIONS ..................................................................................... 42 9 DRUG INTERACTIONS .....................................................................................

46 10 CLINICAL PHARMACOLOGY ............................................................................ 47 11 STORAGE, STABILITY AND DISPOSAL .............................................................. 49 12 SPECIAL HANDLING INSTRUCTIONS................................................................

50 PART II: SCIENTIFIC INFORMATION ....................................................................................... 51 13 PHARMACEUTICAL INFORMATION................................................................. 51 14 CLINICAL TRIALS .............................................................................................

• Patients with known hypersensitivity to ruxolitinib or to any ingredient in the formulation of JAKAVI or component of the container. For a complete listing, see the 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. • Patients who have or have had progressive multifocal leukoencephalopathy (PML) (see 7 WARNINGS AND PRECAUTIONS).