Usual Adult Dose for Myelofibrosis

200 mg orally 2 times a day

Use: Treatment of patients with intermediate or high-risk primary or secondary (post-polycythemia vera OR post-essential thrombocythemia) myelofibrosis (MF) with a platelet count less than 50 times 10(9)/L (50 x 10(9)/L)

Renal Dose Adjustments

Estimated GFR (eGFR) 30 mL/min and over: Data not available
eGFR less than 30 mL/min: Not recommended.

Liver Dose Adjustments

Mild liver dysfunction (Child-Pugh A): No adjustment recommended.
Moderate and severe liver dysfunction (Child-Pugh B and C): Not recommended.

Dose Adjustments

Concomitant kinase inhibitor use: Prior to starting this drug, patients receiving treatment with other kinase inhibitor(s) should taper or discontinue the other kinase inhibitor(s) per manufacturer recommendations.

Planned surgical procedures/other interventions: This drug should be discontinued 7 days before the procedure/intervention, and then should be restarted only after hemostasis is reassured.

ADVERSE REACTIONS:
Diarrhea:

• New onset of diarrhea: Initiate antidiarrheal agent and/or encourage adequate oral hydration
• Grade 3 or 4 diarrhea: Administration should be held until diarrhea resolves to at least Grade 1 (or baseline), and then this drug should be restarted at the last given dose.
• The antidiarrheal regimen should be intensified, and fluid replacement should be provided.
• Recurrent diarrhea: Administration should be held until diarrhea resolves to at least Grade 1 (or baseline), and then this drug should be restarted at 50% of the last given dose once symptoms have resolved.
• Patients restarting treatment: Concomitant antidiarrheal treatment is required.

• Moderate bleeding; intervention indicated: Administration should be held until hemorrhage resolves to at least Grade 1 (or baseline), and then this drug should be restarted at 50% of the last given dose once symptoms have resolved.
• Recurrent hemorrhage: Administration should be held until hemorrhage resolves, and then this drug should be restarted at 50% of the last given dose.
• Severe bleeding; invasive intervention, transfusion, and/or hospitalization indicated: Administration should be held until hemorrhage resolved, and then this drug should be restarted at 50% of the last given dose.
• Recurrent bleeding: Treatment should be discontinued.
• Life-threatening bleeding; urgent intervention indicated: Treatment should be discontinued.

• QT prolongation greater than 500 msec OR greater than 60 msec from baseline: Administration should be held.
• QT prolongation resolves to 480 msec (or baseline) within 1 week: Treatment should be restarted at the same dose.
• Time to resolution is more than 1 week: Treatment should be restarted at a lower dose.

• Clinically significant worsening thrombocytopenia lasting greater than 7 days: Administration should be held, and then this drug should be restarted at 50% of the last given dose once symptoms have resolved.
• Recurrent thrombocytopenia: Administration should be held, and then this drug should be restarted at 50% of the last given dose once symptoms have resolved.

Precautions

CONTRAINDICATIONS:

• Patients concomitantly using strong CYP450 3A4 inducers or inhibitors

Dialysis

eGFR less than 15 and hemodialysis: Not recommended.
Peritoneal dialysis: Data not available

Other Comments

Administration advice:

• This drug may be taken without regard to meals
• Swallow the capsules whole; do not break, chew, or open the capsules.
• Missed dose: Patients should take the next prescribed dose at its scheduled time; extra doses should not be taken to replace the missed dose.

• Store below 30C (86F); keep in the original bottle to protect from light.

• This drug was granted accelerated approval based on spleen volume reduction observed in clinical trials; continued approval may be contingent upon verified clinical benefit in confirmatory trials.

• Cardiovascular: ECG (before and during treatment as necessary)
• Gastrointestinal: New/worsening diarrhea
• Hematologic: CBC and coagulation testing (before and during treatment as necessary)
• Immunologic: Signs/symptoms of infection

• Patients should inform their healthcare providers that they are currently receiving treatment with this drug, especially if they are undergoing planned invasive or elective procedures.
• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.
• Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).