JAKAFI

JAKAFI- ruxolitinib tablet
Incyte Corporation

1. INDICATIONS AND USAGE

1.1 Myelofibrosis

Jakafi is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults.

1.2 Polycythemia Vera

Jakafi is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

1.3 Acute Graft-Versus-Host Disease

Jakafi is indicated for treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients 12 years and older.

1.4 Chronic Graft-Versus-Host Disease

Jakafi is indicated for treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

2. DOSAGE AND ADMINISTRATION

​ 2.1 Monitoring to Assess Safety

​ Prior to Jakafi treatment:

• ​ Perform a complete blood count [see Warnings and Precautions (5.1)].
• ​ Inquire about past infections, including tuberculosis, herpes simplex, herpes zoster, and hepatitis B [see Warnings and Precautions (5.2)].

​ During treatment with Jakafi:

• ​ Perform a complete blood count every 2 to 4 weeks until doses are stabilized, and then as clinically indicated [see Warnings and Precautions (5.1)].
• ​ Assess lipid parameters approximately 8-12 weeks following initiation of Jakafi therapy [see Warnings and Precautions (5.5)].

2.2 Recommended Dosage for Myelofibrosis

The recommended starting dose of Jakafi is based on platelet count (Table 1). Doses may be titrated based on safety and efficacy.

Table 1: Jakafi Starting Doses for Myelofibrosis

Platelet Count	Starting Dose
Greater than 200 x 109 /L	20 mg orally twice daily
100 x 109 /L to 200 x 109 /L	15 mg orally twice daily
50 x 109 /L to less than 100 x 109 /L	5 mg orally twice daily

Dose Modification Guidelines for Hematologic Toxicity for Patients with Myelofibrosis Starting Treatment with a Platelet Count of 100 x 10⁹ /L or Greater

Treatment Interruption and Restarting Dosing

Interrupt treatment for platelet counts less than 50 x 10⁹ /L or absolute neutrophil count (ANC) less than 0.5 x 10⁹ /L.

After recovery of platelet counts above 50 x 10⁹ /L and ANC above 0.75 x 10⁹ /L, dosing may be restarted. Table 2 illustrates the maximum allowable dose that may be used in restarting Jakafi after a previous interruption.

Table 2: Myelofibrosis: Maximum Restarting Doses for Jakafi after Safety Interruption for Thrombocytopenia for Patients Starting Treatment with a Platelet Count of 100 x 10⁹ /L or Greater

* Maximum doses are displayed. When restarting, begin with a dose at least 5 mg twice daily below the dose at interruption.
Current Platelet Count	Maximum Dose When Restarting Jakafi Treatment *
Greater than or equal to 125 x 109 /L	20 mg twice daily
100 to less than 125 x 109 /L	15 mg twice daily
75 to less than 100 x 109 /L	10 mg twice daily for at least 2 weeks; if stable, may increase to 15 mg twice daily
50 to less than 75 x 109 /L	5 mg twice daily for at least 2 weeks; if stable, may increase to 10 mg twice daily
Less than 50 x 109 /L	Continue hold

Following treatment interruption for ANC below 0.5 x 10⁹ /L, after ANC recovers to 0.75 x 10⁹ /L or greater, restart dosing at the higher of 5 mg once daily or 5 mg twice daily below the largest dose in the week prior to the treatment interruption.

Dose Reductions Dose reductions should be considered if the platelet counts decrease as outlined in Table 3 with the goal of avoiding dose interruptions for thrombocytopenia.

Table 3: Myelofibrosis: Dosing Recommendations for Thrombocytopenia for Patients Starting Treatment with a Platelet Count of 100 x 10⁹ /L or Greater

	Dose at Time of Platelet Decline
Platelet Count	25 mg twicedaily	20 mg twicedaily	15 mg twicedaily	10 mg twicedaily	5 mg twicedaily
	NewDose	NewDose	NewDose	NewDose	NewDose
100 to less than 125 x 109 /L	20 mg twicedaily	15 mg twicedaily	No Change	No Change	No Change
75 to less than 100 x 109 /L	10 mg twicedaily	10 mg twicedaily	10 mg twicedaily	NoChange	NoChange
50 to less than 75 x 109 /L	5 mg twicedaily	5 mg twicedaily	5 mg twicedaily	5 mg twicedaily	NoChange
Less than 50 x 109 /L	Hold	Hold	Hold	Hold	Hold