Generic Name and Formulations:
Ruxolitinib 5mg, 10mg, 15mg, 20mg, 25mg; tabs.
Company:
Incyte Corporation
Indications for JAKAFI:
Treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.
Adult Dose for JAKAFI:
Doses may be given by NG tube if unable to swallow tabs. Platelets >200X109/L: initially 20mg twice daily. Platelets 100–200X109/L: initially 15mg twice daily. May increase doses by 5mg twice daily to a max of 25mg twice daily; do not increase during the first 4wks of therapy and not more frequently than every 2wks. Discontinue treatment after 6mos if no reduction in spleen size or symptom improvement. Interrupt treatment if platelets <50X109/L. May restart or increase after recovery of platelets (see literature for max allowable restarting doses). Consider dose reductions if platelets decrease but remain ≥50X109/L (see literature). Concomitant strong CYP3A4 inhibitors: initially 10mg twice daily if platelets ≥100X109/L; if platelets <100X109/L: avoid. Moderate or severe renal impairment (CrCl 15–59mL/min) and platelets between 100–150X109/L: initially 10mg twice daily. ESRD (CrCl <15mL/min) on dialysis with platelets between 100–200X109/L: 15mg after dialysis session; if with platelets >200X109/L: 20mg after dialysis session. ESRD not requiring dialysis, moderate or severe renal impairment with platelets <100X109/L: avoid. Hepatic impairment with platelets between 100–150X109/L: initially 10mg twice daily; if platelets <100X109/L: avoid.
Children's Dose for JAKAFI:
Not established.
Pharmacological Class:
Kinase inhibitor.
Warnings/Precautions:
Monitor for thrombocytopenia, anemia, neutropenia; withhold or reduce dose if occur. Obtain CBC and platelets before initiating therapy, every 2–4 weeks until doses are stabilized, and then as clinically indicated. Risk of serious bacterial, mycobacterial, fungal, and viral infections; eva luate and treat if signs/symptoms occur. Confirm resolution of active infections before starting. Renal or hepatic impairment. Pregnancy (Cat. C). Nursing mothers: not recommended.
Interactions:
Potentiated by strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and mild or moderate CYP3A4 inhibitors (eg, erythromycin). Antagonized by CYP3A4 inducers (eg, rifampin).
Adverse Reactions:
Thrombocytopenia, anemia, neutropenia, bruising, dizziness, headache, UTIs, weight gain, flatulence, herpes zoster.
How Supplied:
Tabs—60
Jakafi Approved for Myelofibrosis
Incyte announced that the FDA has approved Jakafi (ruxolitinib), an oral JAK1 and JAK2 inhibitor, for the treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF. This approval was based on results from two randomized Phase 3 trials (COMFORT-I and COMFORT-II), which demonstrated that patients treated with Jakafi experienced significant reductions in splenomegaly.
The COMFORT-I trial compared Jakafi to placebo in 309 patients with primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF. The trial met the primary endpoint, showing that 41.9% of patients treated with Jakafi experienced a ≥35% reduction in spleen volume at 24 weeks, compared with 0.7% of patients taking placebo (P<0.0001). At Week 24, the percentage of patients with ≥50% improvement in the MFSAF Total Symptom Score was 45.9% and 5.3% in patients treated with Jakafi and placebo, respectively (P<0.0001), with a median time to response of less than four weeks.The COMFORT-II trial compared Jakafi to best available therapy in 219 patients with primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF. This trial also met the primary endpoint, showing that 28.5% of patients treated with Jakafi experienced a ≥35% reduction in spleen volume at 48 weeks, compared with 0% of patients in the best available therapy arm (P<0.0001).
Expanded Dosing, Safety Information for Jakafi
Expanded Dosing, Safety Information for Jakafi Incyte announced that the FDA has updated prescribing information for Jakafi (ruxolitinib) tablets to include new recommended dosing guidance for patients with low platelet counts as well as additional safety information.
Jakafi is a JAK1 and JAK2 inhibitor indicated for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis.
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The update recommends a new starting dose of 5mg twice daily for patients with baseline platelet counts 50–90 x 109/L (50,000–100,000). In addition, the update includes options for subsequent dose modifications based on safety and efficacy.
The FDA approved this dosing update based on a supplemental New Drug Application (sNDA), which included data from an ongoing Phase 2 study (Study 258) of patients with baseline platelet counts of 50,000–100,000. The safety and efficacy data were general consistent with the results from the Phase 3 COMFORT-I and COMFORT-II program.
In addition, new safety information has been added to the Warnings and Precautions section that states: "Progressive multifocal leukoencephalopathy (PML) has been reported with ruxolitinib treatment for myelofibrosis. If PML is suspected, stop Jakafi and eva luate."
The Patient Counseling Information section has also been updated to advise healthcare professionals to inform patients about the early signs and symptoms of PML.
