RUXIENCE CONCENTRATE FOR SOLUTION FOR INFUSION 100mg/10mL

INFUSION, SOLUTION CONCENTRATE

**4.2 Posology and method of administration** **General** Substitution by any other biological medicinal product requires the consent of the prescribing physician. RUXIENCE should always be administered in an environment where full resuscitation facilities are immediately available, and under the close supervision of an experienced physician. The safety and efficacy of alternating or switching between RUXIENCE and products that are biosimilar but not deemed interchangeable to RUXIENCE has not been established. Therefore, the benefit/risk of alternating or switching need to be carefully considered. **Premedication and prophylactic medications** Premedication consisting of an analgesic/anti-pyretic (e.g. paracetamol) and an antihistaminic drug (e.g. diphenhydramine), should always be given before each administration of RUXIENCE. Premedication with corticosteroids should also be considered. Premedication with glucocorticoids should be considered if RUXIENCE is not given in combination with glucocorticoid-containing chemotherapy for treatment of non-Hodgkin’s lymphoma. Patients should be closely monitored for the onset of cytokine release syndrome (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Patients who develop evidence of severe reactions, especially severe dyspnoea, bronchospasm and hypoxia should have the infusion interrupted immediately. The patient should then be evaluated for evidence of tumour lysis syndrome including appropriate laboratory tests and, for pulmonary infiltration, with a chest x-ray. The infusion should not be restarted until complete resolution of all symptoms, and normalisation of laboratory values and chest x-ray findings. At this time, the infusion can be initially resumed at not more than one-half the previous rate. If the same severe adverse reactions occur for a second time the decision to stop the treatment should be seriously considered on a case by case basis. Mild or moderate infusion-related reactions (see section 4.8 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_) usually respond to a reduction in the rate of infusion. The infusion rate may be increased upon improvement of symptoms. **Dosage adjustments during treatment** No dose reductions of RUXIENCE are recommended. When RUXIENCE is given in combination with CVP chemotherapy, standard dose reductions for the chemotherapeutic medicinal products should be applied. **Method of administration** The prepared RUXIENCE solution should be administered as an intravenous infusion through a dedicated line. It must not be administered as an intravenous injection or bolus infusion. **_Infusion rate_** **_First intravenous infusion_** The recommended initial infusion rate is 50 mg/h; subsequently, the rate can be escalated in 50 mg/h increments every 30 minutes to a maximum of 400 mg/h. **_Subsequent intravenous infusions_** Subsequent infusions of RUXIENCE can be started at a rate of 100 mg/h and increased by 100 mg/h increments every 30 minutes to a maximum of 400 mg/h. **Standard dosage** **_Low-grade or follicular non-Hodgkin’s lymphoma_** **_Initial treatment_** - Monotherapy The recommended dosage of RUXIENCE used as monotherapy for adult patients is 375 mg/m2 body surface area, administered as an intravenous infusion once weekly for 4 weeks. - Combination therapy The recommended dosage of RUXIENCE in combination with CVP chemotherapy is 375 mg/m2 body surface area for 8 cycles (21 days/cycle), administered on day 1 of each chemotherapy cycle after intravenous administration of the corticosteroid component of CVP. RUXIENCE has shown acceptable safety in combination with other chemotherapies e.g. CHOP. **_Re-treatment following relapse_** Patients who have responded to RUXIENCE initially have been treated again with RUXIENCE at a dose of 375 mg/m2 body surface area, administered as an intravenous infusion once weekly for 4 weeks (see section 5.1, Re-treatment, weekly for 4 doses – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **_Maintenance treatment_** _Previously untreated follicular lymphoma_ The recommended dose of RUXIENCE used as a maintenance treatment for patients with previously untreated follicular lymphoma who have responded to induction treatment is: 375 mg/m2 body surface area once every 2 months (starting 2 months after the last dose of induction therapy) until disease progression or for a maximum period of two years. _Relapsed/refractory follicular lymphoma_ Patients who have responded to induction treatment may receive maintenance therapy with RUXIENCE given at 375 mg/m2 body surface area once every 3 months until disease progression or for a maximum period of two years. **_Diffuse large B-cell non-Hodgkin’s lymphoma_** RUXIENCE should be used in combination with CHOP chemotherapy. The recommended dosage of RUXIENCE is 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle after intravenous administration of the corticosteroid component of CHOP. The other components of CHOP (cyclophosphamide, doxorubicin and vincristine) should be given after the administration of RUXIENCE. Safety and efficacy of RUXIENCE have not been established in combination with other chemotherapies. **_Chronic lymphocytic leukaemia_** Prophylaxis with adequate hydration and administration of uricostatics starting 48 hours prior to start of therapy is recommended for CLL patients to reduce the risk of tumour lysis syndrome. For CLL patients whose lymphocyte counts are >25 x 109/L, it is recommended to administer prednisone/prednisolone 100 mg intravenous shortly before infusion with RUXIENCE to decrease the rate and severity of acute infusion reactions and/or cytokine release syndrome. The recommended dosage of RUXIENCE for CLL is 375 mg/m2 in the first cycle and 500 mg/m2 in cycles 2–6, in combination with FC, administered every 28 days (see Method of administration, Infusion rate). **_Rheumatoid arthritis_** A course of RUXIENCE consists of two 1000 mg intravenous infusions. The recommended dosage of RUXIENCE is 1000 mg by intravenous infusion followed by a second 1000 mg intravenous infusion two weeks later (see Method of administration, Infusion rate). Patients may receive further courses of treatment, based on signs and symptoms of disease. In clinical studies, no patient received a second course of rituximab treatment within 16 weeks of the first infusion of the first course. The time interval between courses was variable, with the majority of patients receiving further therapy 6–12 months after the previous course. Some patients required even less frequent re-treatment. The efficacy and safety of further courses is comparable to the first course (see sections 4.8, Experience from rheumatoid arthritis and 5.1, Clinical/efficacy Studies, Chronic lymphocytic leukaemia – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Rheumatoid arthritis patients should receive treatment with 100 mg intravenous methylprednisolone 30 minutes prior to RUXIENCE to decrease the rate and severity of acute infusion reactions (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _Alternative subsequent, faster, infusions schedule (rheumatoid arthritis only)_ In rheumatoid arthritis, with a dose of 1000 mg RUXIENCE, if there are no infusion-related reactions or other reasons to slow or cease the infusion, the standard infusion schedules shown above result in an estimated duration of infusion of 4 hours 15 minutes for the first infusion and 3 hours 15 minutes for the second infusion in each course. If patients did not experience a serious infusion-related adverse event with their first or subsequent infusions of a dose of 1000 mg RUXIENCE administered over the standard infusion schedule, a more rapid infusion can be administered for second and subsequent infusions using the same concentration as in previous infusions (4 mg/mL in a 250 mL volume). Initiate at a rate of 250 mg/h for the first 30 minutes and then 600 mg/h for the next 90 minutes. If the more rapid infusion is tolerated, this infusion schedule can be used when administering subsequent infusions. With this infusion schedule, the 1000 mg/250 mL infusion will generally be completed in 2 hours. Patients who have clinically significant cardiovascular disease including arrhythmias or previous serious infusion reactions to any prior biologic therapy or to rituximab, should not be administered the more rapid infusion. **Special dosage instructions** **_Paediatric use_** The safety and efficacy of rituximab in children and adolescents (<18 years) have not been established. Hypogammaglobulinaemia has been observed in paediatric patients treated with rituximab, in some cases severe and requiring long-term immunoglobulin substitution therapy. The consequences of long-term B-cell depletion in paediatric patients are unknown. **_Geriatric use_** No dose adjustment is required in patients aged ≥65 years of age.