Jakavi Tablet 20 mg (Ruxolitinib Phosphate)

Adult dose

Treatment with this medicine should be initiated by a physician experienced in administering anticancer agents. This medicine is taken orally and may be taken with or without food. If a dose is missed, the patient should not take an additional dose and should take the next prescribed dose. Treatment with this medicine for myelofibrosis and polycythemia vera may be continued as long as the benefit/risk ratio remains positive. However, if spleen size has not decreased or symptoms have not improved after 6 months of treatment, treatment with this medicine should be discontinued. In patients with graft-versus-host disease who respond to treatment, tapering the dose of this medicine may be considered after corticosteroids have been discontinued. A 50% dose reduction every 2 months is recommended. If signs or symptoms of graft-versus-host disease recur during or after dose tapering, a dose increase should be considered. Blood cell counts: A complete blood count (CBC) must be obtained before starting treatment with this medicine. CBCs should also be monitored every 2 weeks ∼ 4 weeks until the dose has stabilized, and thereafter as clinically indicated. Myelofibrosis: The recommended initial dose of this medicine is based on the platelet count. 50,000∼100,000/mm3: 10mg twice daily 100,000∼200,000/mm3: 15mg twice daily >200,000/mm3: 20mg twice daily Polycythemia vera and graft-versus-host disease: 10mg twice daily The dose should be adjusted based on safety and efficacy. Myelofibrosis and polycythemia vera If the response is considered inadequate and blood cell counts are adequate, the dose may be increased by up to 5mg twice daily; the maximum dose of this medicine is 25mg twice daily. The initial dose should be maintained for the first 4 weeks after starting treatment, and thereafter the dose should not be increased more frequently than every 2 weeks. Treatment should be discontinued if the platelet count is below 50,000/mm3 or the absolute neutrophil count is below 500/mm3. When used to treat polycythemia vera, treatment should be discontinued if hemoglobin is below 8 g/dL. When blood cell counts recover to at least these levels, treatment may be resumed at 5 mg twice daily, with careful monitoring of blood cell counts and gradual dose increases. In myelofibrosis, if the platelet count decreases as shown in the following table, dose reduction should be considered to avoid treatment interruption due to thrombocytopenia. Platelet count 100,000/mm3 or more and below 125,000/mm3: for a dose of 25 mg twice daily, new dose 20 mg twice daily; for a dose of 20 mg twice daily, new dose 15 mg twice daily; for a dose of 15 mg twice daily, new dose 15 mg twice daily; for a dose of 10 mg twice daily, new dose 10 mg twice daily; for a dose of 5mg twice daily, new dose 5 mg twice daily Platelet count 75,000/mm3 or more and below 100,000/mm3: for a dose of 25 mg twice daily, new dose 10 mg twice daily; for a dose of 20 mg twice daily, new dose 10 mg twice daily; for a dose of 15 mg twice daily, new dose 10 mg twice daily; for a dose of 10 mg twice daily, new dose 10 mg twice daily; for a dose of 5mg twice daily, new dose 5 mg twice daily Platelet count 50,000/mm3 or more and below 75,000/mm3: for a dose of 25 mg twice daily, new dose 5 mg twice daily; for a dose of 20 mg twice daily, new dose 5 mg twice daily; for a dose of 15 mg twice daily, new dose 5 mg twice daily; for a dose of 10 mg twice daily, new dose 5 mg twice daily; for a dose of 5mg twice daily, new dose 5 mg twice daily Platelet count below 50,000/mm3: temporarily interrupt treatment for doses of 25 mg twice daily, 20 mg twice daily, 15 mg twice daily, 10 mg twice daily, or 5mg twice daily When used to treat polycythemia vera, dose reduction should be considered if hemoglobin decreases to below 12 g/dL, and dose reduction is recommended if hemoglobin is below 10 g/dL. Hemoglobin 12 g/dL or higher and platelet count 100,000/mm3 or higher: no dose adjustment required Hemoglobin 10 g/dL or higher and below 12 g/dL and platelet count 75,000/mm3 or higher and below 100,000/mm3: consider dose reduction to prevent treatment interruption due to anemia and thrombocytopenia Hemoglobin 8 g/dL or higher and below 10 g/dL or platelet count 50,000/mm3 or higher and below 75,000/mm3: reduce the dose to 5mg twice daily; patients already receiving 5mg twice daily should reduce the dose to 5mg once daily Hemoglobin below 8 g/dL or platelet count below 50,000/mm3: discontinue treatment Graft-versus-host disease In patients with graft-versus-host disease, dose reduction and temporary treatment interruption may be required if thrombocytopenia, neutropenia, or increased total bilirubin occurs after standard supportive care, including growth factors, anti-infective therapy, and transfusions. A reduction by one dose level is recommended (reduce from 10 mg twice daily to 5mg twice daily or from 5mg twice daily to 5mg once daily). Patients who do not tolerate a dose of 5mg once daily of this medicine should discontinue treatment. Platelet count below 20,000/mm3: Reduce this medicine by one dose level. If the platelet count reaches 20,000/mm3 or higher within 7 days, the dose may be increased to the initial dose level; otherwise, maintain the reduced dose. Platelet count below 15,000/mm3: Interrupt treatment with this medicine until the platelet count is 20,000/mm3 or higher, then resume treatment at one dose level lower. Absolute neutrophil count (ANC) 500/mm3 or higher and below 750/mm3: Reduce this medicine by one dose level. Resume treatment at the initial dose when the ANC exceeds 1,000/mm3. Absolute neutrophil count (ANC) below 500/mm3: Interrupt treatment with this medicine until the ANC exceeds 500/mm3, then resume treatment at one dose level lower. Treatment may be resumed at the initial dose when the ANC exceeds 1,000/mm3. Increased total bilirubin in patients without hepatic graft-versus-host disease Greater than 3.0 x ULN and up to 5.0 x ULN: Continue treatment with this medicine at one dose level lower until total bilirubin is 3.0 x ULN or lower. Greater than 5.0 x ULN and up to 10.0 x ULN: Interrupt treatment with this medicine for up to 14 days until total bilirubin is 3.0 x ULN or lower. If total bilirubin is 3.0 x ULN or lower, treatment may be resumed at the current dose. If total bilirubin does not become 3.0 x ULN or lower after 14 days, resume treatment at one dose level lower. Greater than 10.0 x ULN: Interrupt treatment with this medicine until total bilirubin is 3.0 x ULN or lower, then resume treatment at one dose level lower. Increased total bilirubin in patients with hepatic graft-versus-host disease Greater than 3.0 x ULN: Continue treatment with this medicine at one dose level lower until total bilirubin is 3.0 x ULN or lower. Dose adjustment when coadministered with a strong CYP3A4 inhibitor or fluconazole In patients with myelofibrosis and polycythemia vera receiving this medicine with a strong CYP3A4 inhibitor, or in patients with myelofibrosis, polycythemia vera, and graft-versus-host disease receiving this medicine with a dual moderate inhibitor of CYP2C9 and CYP3A4 enzymes, such as fluconazole, the total daily dose of this medicine should be reduced by approximately 50%. Adjust the dose by reducing the twice-daily dose or, if twice-daily administration is not possible, by reducing the frequency to the corresponding once-daily dose. When this medicine is coadministered with fluconazole, fluconazole should not exceed 200mg per day. When this medicine is coadministered with a strong CYP3A4 inhibitor or a dual moderate inhibitor of CYP2C9 and CYP3A4 enzymes, hematologic parameters and clinical signs or symptoms of adverse reactions to this medicine should be monitored more frequently. No dose adjustment is required when this medicine is coadministered with mild or moderate CYP3A4 inhibitors. Patients with renal impairment The recommended initial dose for myelofibrosis in patients with moderate (creatinine clearance 30 mL/min or higher and below 50 mL/min) or severe renal impairment (creatinine clearance below 30 mL/min) is 10mg twice daily. The recommended initial dose for polycythemia vera and graft-versus-host disease in patients with moderate or severe renal impairment is 5mg twice daily. Safety and efficacy should be carefully monitored during treatment with this medicine, and further dose adjustments may be required. There are limited data to determine the optimal dose for myelofibrosis in patients with end-stage renal disease (ESRD) requiring hemodialysis. Based on available findings in these patients, the recommended initial dose is a single dose of 15mg for patients with a platelet count of 100,000∼200,000/mm3 and a single dose of 20mg for patients with a platelet count greater than 200,000/mm3. The dose should be administered only on the day of dialysis, after dialysis, and should not be administered more than once daily. The dose should be adjusted with careful monitoring of safety and efficacy. No data are available on administration to patients undergoing peritoneal dialysis or continuous venovenous hemofiltration. The recommended initial dose for polycythemia vera and graft-versus-host disease in patients with ESRD requiring hemodialysis is a single dose of 10mg, administered only on the day of dialysis, after dialysis; safety and efficacy should be carefully monitored. Patients with hepatic impairment The recommended initial dose for myelofibrosis in patients with hepatic impairment should be reduced to 10mg twice daily, and the recommended initial dose for polycythemia vera should be reduced to 5mg twice daily. Subsequent doses should be adjusted with careful monitoring of safety and efficacy. No change to the initial dose is recommended in patients with graft-versus-host disease who have hepatic impairment, including hepatic graft-versus-host disease. In patients with hepatic involvement of graft-versus-host disease and total bilirubin levels greater than 3 x ULN, toxicity and blood counts should be monitored more frequently, and a reduction by one dose level may be considered. Elderly patients No dose adjustment is required in elderly patients.

Child dose

Pediatric patients aged 12 years and older with graft-versus-host disease: The dose of this drug is the same as that for adults. Patients under 12 years: The safety and efficacy of this drug have not been established.

This medication can decrease platelet, red blood cell, and neutrophil counts in the blood, so a complete blood count must be performed before administration. If platelet counts are too low or neutrophil counts are very low, therapy should be discontinued. Myelofibrosis patients may experience more significant platelet reduction, so caution is required. Thrombocytopenia and anemia usually recover with a dose reduction or temporary discontinuation of the drug, and blood transfusion may be necessary if needed. Neutropenia can also be managed by temporarily discontinuing the medication, but regular monitoring of blood counts is important. Patients with allergies to this drug and its additives or certain genetic lactose metabolism disorders should not use this medication. This drug can cause various adverse reactions, particularly anemia, thrombocytopenia, neutropenia, bruising, dizziness, and urinary tract infections. Liver function tests (ALT and AST) may show elevations, thus regular monitoring of liver function is necessary. The risk of infections is increased during treatment, so any symptoms of infection should be reported to a medical professional immediately, and latent infections like tuberculosis should be evaluated beforehand. Be aware of the initial symptoms of herpes zoster, and rapid treatment is required if symptoms develop. A rare disease called progressive multifocal leukoencephalopathy, which can affect the nervous system, can occur, so neurological symptoms should be closely monitored. Sudden discontinuation of this medication may lead to a recurrence of myelofibrosis symptoms, so gradual dose reduction is recommended. The risk of skin cancer may increase, so regular skin examinations are advisable. This medication may increase blood lipid levels, necessitating lipid level monitoring and treatment if needed. Patients with cardiovascular disease risk should carefully evaluate the risks and benefits before and during therapy. The risk of thrombosis is present, so immediate assessment and treatment are required if symptoms of thrombosis appear. This medication may interact with other drugs, and dose adjustments may be necessary when used in combination with specific enzyme inhibitors or inducers. Use during pregnancy is not recommended, and women of childbearing age should use effective contraception while taking this medication. Nursing mothers should consult with medical professionals regarding possible passage of this drug into breast milk, potentially requiring either discontinuation of breastfeeding or the medication. There is no antidote for overdose, so recommended dosages must be strictly adhered to, and appropriate supportive treatment is needed in case of an overdose. Keep this medication out of reach of children and avoid transferring it to other containers.

• Thrombocytopenia
• anemia
• neutropenia
• bruising
• dizziness
• urinary tract infection
• elevated ALT
• elevated AST
• hypertriglyceridemia
• weight gain

This medication may be sensitive to air and moisture, so it should be stored in a tightly sealed container. It is advisable to maintain room temperature between 1 degree and 25 degrees Celsius. This will help preserve the medication's efficacy for an extended period.

Appearance

White or off-white rectangular tablets

Package unit

56 tablets (14 tablets/PTP packaging x 4)