Jakavi

Jakavi treatment should only be initiated by a physician experienced in the administration of anti- cancer medicinal products. A complete blood cell count, including a white blood cell count differential, must be performed before initiating therapy with Jakavi.

4). Posology Starting dose Myelofibrosis (MF) The recommended starting dose of Jakavi in MF is based on platelet counts (see Table 1): Table 1 Starting doses in myelofibrosis Platelet count Starting dose Greater than 200 000/mm3 20 mg twice daily 100 000 to 200 000/mm3 15 mg twice daily 75 000 to less than 100 000/mm3 10 mg twice daily 50 000 to less than 75 000/mm3 5 mg twice daily Polycythaemia vera (PV) The recommended starting dose of Jakavi in PV is 10 mg twice daily.

4 Graft versus host disease (GvHD) The recommended starting dose of Jakavi in acute and chronic GvHD is based on age (see Tables 2 and 3): Table 2 Starting doses in acute graft versus host disease Age group Starting dose 12 years old and above 10 mg twice daily 6 years to less than 12 years old 5 mg twice daily 28 days to less than 6 years old 8 mg/m2 twice daily Table 3 Starting doses in chronic graft versus host disease Age group Starting dose 12 years old and above 10 mg twice daily 6 years to less than 12 years old 5 mg twice daily 6 months to less than 6 years old 8 mg/m2 twice daily These starting doses in GvHD can be administered using either the tablet for patients who can swallow tablets whole or the oral solution.

Jakavi can be added to corticosteroids and/or calcineurin inhibitors (CNIs). Dose modifications Doses may be titrated based on efficacy and safety. Myelofibrosis and polycythaemia vera 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. Treatment should be discontinued for platelet counts less than 50 000/mm3 or absolute neutrophil counts less than 500/mm3.

In PV, treatment should also be interrupted when haemoglobin is below 8 g/dl. After recovery of blood counts above these levels, dosing may be re-started at 5 mg twice daily and gradually increased based on careful monitoring of complete blood cell count, including a white blood cell count differential.

Summary of the safety profile Myelofibrosis The most frequently reported adverse drug reactions were thrombocytopenia and anaemia. 8%). Anaemia, thrombocytopenia and neutropenia are dose-related effects. 9%). 2%). In phase 3 clinical studies in MF, neither CTCAE grade 3 or 4 13 hypertriglyceridaemia or increased aspartate aminotransferase, nor CTCAE grade 4 increased alanine aminotransferase or hypercholesterolaemia were observed.

0% of patients. Polycythaemia vera The most frequently reported adverse drug reactions were anaemia and increased alanine aminotransferase. 3%). 6% of the patients, respectively. 9%). 7%). No CTCAE grade 4 increased alanine aminotransferase or hypercholesterolaemia, and one CTCAE grade 4 increased aspartate aminotransferase were observed.

4% of patients. Acute GvHD The most frequently reported adverse drug reactions in REACH2 (adult and adolescent patients) were thrombocytopenia, anaemia, neutropenia, increased alanine aminotransferase and increased aspartate aminotransferase.

The most frequently reported adverse drug reactions in the pool of paediatric patients (adolescents from REACH2 and paediatric patients from REACH4) were anaemia, neutropenia, increased alanine aminotransferase, hypercholesterolaemia and thrombocytopenia.

0%), respectively. 8% of patients in the paediatric pool. 4% of patients in the paediatric pool, respectively. 0% of patients in the paediatric pool, respectively. 9%), respectively. 2%), respectively. 3% of patients in the paediatric pool.

6% of patients in the paediatric pool. 14 Chronic GvHD The most frequently reported adverse drug reactions in REACH3 (adult and adolescent patients) were anaemia, hypercholesterolemia and increased aspartate aminotransferase. The most frequently reported adverse drug reactions in the pool of paediatric patients (adolescents from REACH3 and paediatric patients from REACH5) were neutropenia, hypercholesterolaemia and increased alanine aminotransferase.

Myelosuppression Treatment with Jakavi can cause haematological adverse drug reactions, including thrombocytopenia, anaemia and neutropenia. A complete blood count, including a white blood cell count differential, must be performed before initiating therapy with Jakavi.

2). It has been observed that MF patients with low platelet counts (<200 000/mm3) at the start of therapy are more likely to develop thrombocytopenia during treatment. 8). However, platelet transfusions may be required as clinically indicated.

Patients developing anaemia may require blood transfusions. Dose modifications or interruption for patients developing anaemia may also need to be considered. 1%). 0 g/dl. 8). 8). 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. Treatment with Jakavi should not be started until active serious infections have resolved.

Tuberculosis has been reported in patients receiving Jakavi. Before starting treatment, patients should be evaluated for active and inactive (“latent”) tuberculosis, as per local recommendations. This can include medical history, possible previous contact with tuberculosis, and/or appropriate screening such as lung x-ray, tuberculin test and/or interferon-gamma release assay, as applicable.

Prescribers are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised. Hepatitis B viral load (HBV-DNA titre) increases, with and without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking Jakavi.

1. Pregnancy and lactation.