ABBREVIATED PRESCRIBING INFORMATION
ABBREVIATED PRESCRIBING INFORMATION
Refer to Summary of Product Characteristics (SmPC) before prescribing.
Jakavi (ruxolitinib) 5mg, 10mg, 15mg and 20mg Tablets
PRESENTATION: Tablets containing 5 mg, 10 mg, 15 mg or 20 mg ruxolitinib (as phosphate).
INDICATIONS: Myelofibrosis (MF): Jakavi is indicated for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis. Polycythaemia vera (PV): Jakavi is indicated for the treatment of adult patients with polycythaemia vera who are resistant to or intolerant of hydroxyurea.
DOSAGE AND ADMINISTRATION: Jakavi treatment should only be initiated by a physician experienced in the administration of anti-cancer agents. Perform a complete blood cell count, including a white blood cell count differential, before initiating Jakavi therapy. Monitor complete blood cell counts every 2 to 4 weeks until optimal dose is reached. Administration orally, with or without food. Starting dose: The recommended starting dose of Jakavi in myelofibrosis (MF) is based on platelet counts. The recommended starting dose of Jakavi for adults in MF is 20 mg twice daily (platelet count of >200,000/mm3), 15 mg twice daily (platelet count between 100,000/mm3 and 200,000/mm3), 10 mg twice daily (platelet count between 75,000/mm3 and 100,000/mm3) and 5 mg twice daily (platelet count between 50,000/mm3 and 75,000/mm3). Recommended starting dose of Jakavi in PV is 10mg twice daily. If efficacy is considered insufficient and blood counts are adequate, doses may be increased by a maximum of 5 mg twice daily, up to the maximum dose of 25 mg twice daily. The starting dose should not be increased within the first four weeks of treatment and thereafter no more frequently than at 2-week intervals. Discontinue treatment if platelet counts <50,000/mm3 or absolute neutrophil counts (ANC) <500/ mm3 (MF and PV patients), in PV patients also interrupt treatment if Hg <8g/dl. Dose reduction should be considered if the platelet count decreases during treatment as outlined in Table 1 (aiming to avoid dose interruptions for thrombocytopenia).
| Dose at time of platelet decline |
|---|
| |
25 mg twice daily |
20 mg twice daily |
15 mg twice daily |
10 mg twice daily |
5 mg twice daily |
| Platelet count |
New dose |
| 100,000 to <125,000/mm3 |
20 mg twice daily |
15 mg twice daily |
No change |
No change |
No change |
| 75,000 to <100,000/mm3 |
10 mg twice daily |
10 mg twice daily |
10 mg twice daily |
No change |
No change |
| 100,000 to < 125,000/mm3 |
5 mg twice daily |
5 mg twice daily |
5 mg twice daily |
5 mg twice daily |
No change |
| Less than 50,000/mm33 |
Hold |
Hold |
Hold |
Hold |
Hold |
Table 1 Dosing recommendation for thrombocytopenia.
In PV, additionally dose reduction should be considered if Hg <12 g/dl and recommended if Hg <10 g/dl. Dose should be reduced by approximately 50%, to be administered twice daily when administered with strong CYP3A4 inhibitors or dual inhibitors of CYP2C9 and CYP3A4 enzymes (e.g. fluconazole). Avoid concomitant use with fluconazole doses greater than 200 mg daily. More frequent monitoring (e.g. twice a week) of haematology parameters and of clinical signs and symptoms of ruxolitinib-related adverse drug reactions is recommended. In patient with severe renal impairment (creatinine clearance <30 ml/min), the recommended starting dose based on platelet count for MF patients should be reduced by approximately 50% to be administered twice daily. The recommended starting dose for PV patients with severe renal impairment is 5 mg twice daily. Patients with renal impairment should be carefully monitored with regard to safety and efficacy during Jakavi treatment. For patients with any hepatic impairment, the recommended starting dose based on platelet count should be reduced by approximately 50% to be administered twice daily. Subsequent doses should be adjusted based on careful monitoring of safety and efficacy. No additional dose adjustments are recommended for older people. Safety and efficacy in children aged up to 18 years have not been established. See Section 5.1 of the SmPC for full details. Treatment should be discontinued after 6 months if there has been no reduction in spleen size or improvement in symptoms since initiation of therapy.
CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SmPC. Pregnancy and lactation.
PRECAUTIONS AND WARNINGS: Decrease in blood cell count: hematologic adverse drug reactions, including thrombocytopenia, anaemia and neutropenia have been reported with Jakavi treatment. Complete blood count, including a white blood cell count differential, must be performed before initiating therapy with Jakavi. Dose reduction or interruption may be required in patients developing thrombocytopenia, anaemia and neutropenia. Infections: Patients should be assessed for risk of developing serious infections. Monitor patients for signs and symptoms of infections during Jakavi treatment, and initiate appropriate treatment promptly. Treatment with Jakavi should not be started until active serious infections have resolved. Before starting treatment, patients should be assessed for active and inactive (“latent”) tuberculosis, as per local recommendations. It is recommended to screen for HBV prior to commencing treatment. Hepatic and severe renal impairment: Due to increased Jakavi exposure, dose reduction is required. Progressive multifocal leukoencephalopathy (PML) has been reported with Jakavi treatment. Physicians should be alert for neuropsychiatric symptoms suggestive of PML. If PML is suspected suspend treatment and until PML is excluded. Lipid monitoring and treatment of dyslipidaemia according to clinical guidelines is recommended. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. Physicians should educate patients about early signs and symptoms of herpes zoster, advising that treatment should be sought as early as possible. See Section 4.4 of the SmPC for full details.
INTERACTIONS: Interaction studies have only been performed in adults. Ruxolitinib is eliminated through metabolism catalysed by CYP3A4 and CYP2C9. Thus, medicinal products inhibiting these enzymes can give rise to increased ruxolitinib exposure. Dose reduction recommended when co-administered with strong CYP3A4 inhibitors or dual inhibitors of CYP2C9 and CYP3A4 enzymes. Avoid concommitant use with fluconazole doses greater than 200 mg daily. See Section 4.2 and 4.5 of the SmPC for full details.
FERTILITY, PREGNANCY AND LACTATION: The potential risk for humans is unknown. As a precautionary measure, the use of Jakavi during pregnancy is contraindicated (see section 4.3 of the SmPC). Women of child-bearing potential should use effective contraception during the treatment with Jakavi. Jakavi must not be used during breast-feeding and breast-feeding should therefore be discontinued when treatment is started.
UNDESIRABLE EFFECTS: Very common (≥1/10): Urinary tract infections, Herpes zoster, pneumonia, anaemia, thrombocytopenia, neutropenia, bleeding, bruising, gastrointestinal bleeding, other bleeding, hypercholesterolaemia, hypertriglyceridaemia, weight gain, dizziness, headache, elevated lipase, constipation, raised alanine aminotransferase, raised aspartate aminotransferase, hypertension. Common (≥1/100 to <1/10): Sepsis, pancytopenia, intracranial bleeding, flatulence. Uncommon (≥1/1,000 to <1/100): Tuberculosis, HBV reactivation. Please see Section 4.8 of the SmPC for a full list of adverse drug reactions (ADR) including further information on the frequency category of each ADR for Mylofibrosis and Polycythaemia vera.
PACK SIZE: PVC/PCTFE/Aluminium blister packs containing 14 or 56 tablets or multipacks containing 168 (3 packs of 56) tablets. Not all pack sizes or types may be marketed.
LEGAL CATEGORY: POM
MARKETING AUTHORISATION NUMBER:
U/1/12/773/005 Jakavi 5 mg Tablet
EU/1/12/773/015 Jakavi 10 mg Tablet
EU/1/12/773/008 Jakavi 15 mg Tablet
EU/1/12/773/011 Jakavi 20 mg Tablet
MARKETING AUTHORISATION HOLDER: Novartis Europharm Limited, Vista Building Elm Park, Merrion Road, Dublin 4, Ireland
PRESCRIBING INFORMATION LAST REVISED: July 2021
Full prescribing information is available upon request from: Novartis Ireland Limited, Vista Building, Elm Park Business Park, Merrion Road, Dublin 4. Tel: 01-2601255 or at www.medicines.ie . Detailed information on this product is also available on the website of the European Medicines Agency http://www.ema.europa.eu
