Important Safety Information

JAKAVI^®

Important note: Before prescribing, consult full prescribing information.

Presentation: Tablets containing 5 mg, 10 mg, 15 mg, and 20 mg ruxolitinib.

Indications: ♦Treatment of adult patients with myelofibrosis (MF), including primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. ♦Treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea. ♦Treatment of patients aged 12 years and older with graft-versus-host disease who have inadequate response to corticosteroids or other systemic therapies.

Dosage and administration: ♦Blood cell counts should be performed before initiating Jakavi^®. Complete blood counts should be monitored every 2 to 4 weeks until optimal dose is reached. ♦Administration twice daily at the same time every day, with or without food. ♦Recommended starting dose for adults in MF: 20 mg (platelet count >200,000/mm³), 15 mg (platelet count between 100,000 and 200,000/mm³) and 10 mg (platelet count between 50,000 and 100,000/mm³, twice daily. ♦Recommended starting dose for adults in PV and for pediatrics aged 12 years and older and adults in GvHD: 10 mg twice daily. ♦Dose adjustments are recommended in MF-patients with thrombocytopenia and in GvHD-patients with thrombocytopenia, neutropenia, and hyperbilirubinemia (see full prescribing information). ♦Treatment should be interrupted if platelet counts <50,000/mm³ or ANC <500/mm³ (MF and PV patients) or Hb <8g/dL (in PV patients). ♦In PV, dose reduction to be considered if Hb <12 g/dL and recommended if Hb <10 g/dL. ♦Dose adjustment may be required due to thrombocytopenia or when used with strong CYP3A4 inhibitors or dual moderate inhibitors of CYP2C9 and CYP3A4 enzymes (e.g. fluconazole; avoid daily dose of fluconazole >200 mg). ♦4 weeks after initiating therapy dose may be increased at intervals of greater than 2 weeks to ensure adequate response. ♦Maximum dose is 25 mg twice daily. ♦Treatment to be continued as long as the benefits outweigh the risks for the patient. Tapering in GvHD-patients may be considered in responders who have discontinued corticosteroids. 50% dose reduction every 2 months recommended. If signs or symptoms reoccur during or after the taper, consider treatment re-escalation. ♦Recommend to reduce the starting dose by approximately 50% in MF, PV and GvHD patients with severe renal impairment (Clcr <30 mL/min) and in MF and PV patients with hepatic impairment. Patients diagnosed with renal or hepatic impairment should be monitored and the dose should be reduced as appropriate. ♦No dosage adjustment required for elderly patients. Contraindications: Hypersensitivity to ruxolitinib or to any of the excipients

Warnings and precautions: ♦Decrease in blood cell count: hematologic adverse drug reactions, including thrombocytopenia, anemia and neutropenia, have been reported with Jakavi treatment. Complete blood counts monitoring recommended. Dose reduction or interruption may be required in patients developing thrombocytopenia, anemia and neutropenia. ♦Infections: Serious bacterial, mycobacterial, fungal, viral and other opportunistic infections have occurred in patients treated with Jakavi. Patients should be assessed for the risk of developing serious infections. Physicians should carefully observe patients receiving Jakavi for signs and symptoms of infections and initiate appropriate treatment promptly. Jakavi therapy should not be started until active serious infections have resolved. Tuberculosis cases have been reported. Before starting treatment patients should be evaluated for active and inactive (“latent”) tuberculosis, as per local recommendations. Hepatitis B viral load (HBV-DNA titre) increases have been reported in patients with chronic HBV infections. Patients with chronic HBV infection should be treated and monitored according to clinical guidelines. ♦Herpes zoster: Physician to educate patients about early signs and symptoms of herpes zoster, advising for immediate treatment. ♦Progressive multifocal leukencephalopathy (PML) has been reported. Physicians should be alert for neuropsychiatric symptoms suggestive of PML. If PML suspected suspend treatment until PML is excluded. ♦Non-Melanoma Skin Cancer (NMSC): NMSC, including basal cell, squamous cell, and Merkel cell carcinoma, have been reported in Jakavi treated patients. Periodic skin examination recommended. ♦Lipid Abnormalities/Elevations: Increases in lipid parameters, including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides have been associated with Jakavi. Monitoring and treatment of dyslipidaemia is recommended. ♦Hepatic and severe renal impairment: Due to increased Jakavi exposure, dose reduction is required.

Pregnancy, lactation, females and males of reproductive potential

Pregnancy: Use in pregnancy not recommended.

Breast-feeding: Women taking Jakavi should not breast-feed.

Contraception: Sexually active females should use effective contraception during treatment.

Adverse drug reactions:

Myelofibrosis

Very common (>10%): Urinary tract infections, herpes zoster, pneumonia, anaemia, thrombocytopenia, neutropenia, hypercholesterolaemia, hypertriglyceridaemia, dizziness, headache, constipation, ALT increased, AST increased, hypertension, bruising, weight gain.

Common (1 to 10%): Pancytopenia, flatulence.

Uncommon (0.1 to 1%):Tuberculosis.

Polycythemia vera

Very common (>10%): Urinary tract infections, herpes zoster, anaemia, thrombocytopenia, bruising, hypercholesterolaemia, hypertriglyceridaemia, weight gain, dizziness, headache, constipation, ALT increased, AST increased, hypertension.

Common (1 to 10%): Pneumonia, neutropenia, pancytopenia, flatulence.

Not known (frequency cannot be estimated): Tuberculosis.

Graft versus host disease

Very common (>10%): CMV infections, sepsis, UTI, thrombocytopenia, anemia, neutropenia, pancytopenia, hypercholesterolemia, headache, hypertension, increased lipase, increased Herpes zoster: Physician to educate patients about early signs and symptoms of herpes zoster, advising for immediate treatment. ♦Progressive multifocal leukencephalopathy (PML) has been reported. Physicians should be alert for neuropsychiatric symptoms suggestive of PML. If PML suspected suspend treatment until PML is excluded. ♦Non-Melanoma Skin Cancer (NMSC):NMSC, including basal cell, squamous cell, and Merkel cell carcinoma, have been reported in Jakavi treated patients. Periodic skin examination recommended. ♦Lipid Abnormalities/Elevations: Increases in lipid parameters, including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides have been associated with Jakavi. Monitoring and treatment of dyslipidaemia is recommended. ♦Hepatic and severe renal impairment: Due to increased Jakavi exposure, dose reduction is required.

Pregnancy, lactation, females and males of reproductive potential

Pregnancy: Use in pregnancy not recommended.

Breast-feeding: Women taking Jakavi should not breast-feed.

Contraception: Sexually active females should use effective contraception during treatment.

Adverse drug reactions:

Myelofibrosis

Common (1 to 10%): Pancytopenia, flatulence.

Uncommon (0.1 to 1%):Tuberculosis.

Polycythemia vera

Common (1 to 10%): Pneumonia, neutropenia, pancytopenia, flatulence.

Not known (frequency cannot be estimated): Tuberculosis.

Graft versus host disease

Common (1 to 10%): BK virus infections, weight gain, and constipation.

Interactions: ♦Caution with CYP3A4 inhibitors or dual moderate inhibitors of CYP2C9 and CYP3A4 enzymes. Dose reduction recommended when co-administered with strong CYP3A4 inhibitors in MF and PV patients or dual moderate inhibitors of CYP2C9 and CYP3A4 enzymes in MF, PV and GvHD patients. Avoid fluconazole daily doses >200 mg.

Packs and prices:Country-specific.

Legal classification:Country-specific.

Important Safety Information