Rixathon Dosage/Direction for Use

Rituximab should be administered under the close supervision of an experienced healthcare professional, and in an environment where full resuscitation facilities are immediately available (see Precautions).
Premedication consisting of an anti-pyretic and an antihistaminic, e.g. paracetamol and diphenhydramine, should always be given before each administration of rituximab.
In patients with non-Hodgkin's lymphoma and chronic lymphocytic leukaemia, premedication with glucocorticoids should be considered if rituximab is not given in combination with glucocorticoid-containing chemotherapy. In patients with rheumatoid arthritis, premedication with 100 mg intravenous methylprednisolone should be completed 30 minutes prior to rituximab infusions to decrease the incidence and severity of infusion related reactions (IRRs).
In patients with granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis, methylprednisolone given intravenously for 1 to 3 days at a dose of 1,000 mg per day is recommended prior to the first infusion of rituximab (the last dose of methylprednisolone may be given on the same day as the first infusion of rituximab). This should be followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day, and tapered as rapidly as possible based on clinical need) during and after rituximab treatment.
Posology: It is important to check the medicinal product labels to ensure that the appropriate formulation is being given to the patient, as prescribed.
Non-Hodgkin's lymphoma: Follicular non-Hodgkin's lymphoma: Combination therapy: The recommended dose of rituximab in combination with chemotherapy for induction treatment of previously untreated or relapsed/ refractory patients with follicular lymphoma is: 375 mg/m² body surface area per cycle, for up to 8 cycles.
Rituximab should be administered on day 1 of each chemotherapy cycle, after intravenous administration of the glucocorticoid component of the chemotherapy if applicable.
Maintenance therapy: Previously untreated follicular lymphoma: The recommended dose of rituximab 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: The recommended dose of rituximab used as a maintenance treatment for patients with relapsed/refractory follicular lymphoma who have responded to induction treatment is: 375 mg /m² body surface area once every 3 months (starting 3 months after the last dose of induction therapy) until disease progression or for a maximum period of two years.
Monotherapy: Relapsed/refractory follicular lymphoma: The recommended dose of rituximab monotherapy used as induction treatment for adult patients with stage III-IV follicular lymphoma who are chemoresistant or are in their second or subsequent relapse after chemotherapy is: 375 mg/m² body surface area, administered as an intravenous infusion once weekly for four weeks.
For retreatment with rituximab monotherapy for patients who have responded to previous treatment with rituximab monotherapy for relapsed/refractory follicular lymphoma, the recommended dose is: 375 mg/m² body surface area, administered as an intravenous infusion once weekly for four weeks (see Pharmacology: Pharmacodynamics under Actions).
Diffuse large B cell non-Hodgkin's lymphoma: Rituximab should be used in combination with CHOP chemotherapy. The recommended dose is 375 mg/m² body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles after intravenous infusion of the glucocorticoid component of CHOP. Safety and efficacy of rituximab have not been established in combination with other chemotherapies in diffuse large B cell non- Hodgkin's lymphoma.
Dose adjustments during treatment: No dose reductions of rituximab are recommended. When rituximab is given in combination with chemotherapy, standard dose reductions for the chemotherapeutic medicinal products should be applied.
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 rituximab to decrease the rate and severity of acute infusion reactions and/or cytokine release syndrome.
The recommended dose of rituximab in combination with chemotherapy for previously untreated and relapsed/refractory patients is 375 mg/m² body surface area administered on day 0 of the first treatment cycle followed by 500 mg/m² body surface area administered on day 1 of each subsequent cycle for 6 cycles in total. The chemotherapy should be given after rituximab infusion.
Rheumatoid arthritis: Patients treated with rituximab must be given the patient alert card with each infusion.
A course of rituximab consists of two 1,000 mg intravenous infusions. The recommended dose of rituximab is 1,000 mg by intravenous infusion followed by a second 1,000 mg intravenous infusion two weeks later.
The need for further courses should be evaluated 24 weeks following the previous course. Retreatment should be given at that time if residual disease activity remains, otherwise retreatment should be delayed until disease activity returns.
Available data suggest that clinical response is usually achieved within 16 to 24 weeks of an initial treatment course. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within this time period.
Granulomatosis with polyangiitis and microscopic polyangiitis: Patients treated with rituximab must be given the patient alert card with each infusion.
The recommended dose of rituximab for induction of remission therapy of granulomatosis with polyangiitis and microscopic polyangiitis is 375 mg/m² body surface area, administered as an intravenous infusion once weekly for 4 weeks (four infusions in total).
Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with granulomatosis with polyangiitis or microscopic polyangiitis during and following rituximab treatment, as appropriate.
Special populations: Paediatric population: The safety and efficacy of rituximab in children below 18 years have not been established. No data are available.
Elderly: No dose adjustment is required in elderly patients (aged >65 years).
Method of administration: Rituximab is for intravenous use. The prepared rituximab solution should be administered as an intravenous infusion through a dedicated line. It should not be administered as an intravenous push or bolus.
Patients should be closely monitored for the onset of cytokine release syndrome (see Precautions). Patients who develop evidence of severe reactions, especially severe dyspnoea, bronchospasm or hypoxia should have the infusion interrupted immediately. Patients with non-Hodgkin's lymphoma should then be evaluated for evidence of tumour lysis syndrome including appropriate laboratory tests and, for pulmonary infiltration, with a chest X-ray. In all patients, 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 (IRR) (Adverse Reactions) usually respond to a reduction in the rate of infusion. The infusion rate may be increased upon improvement of symptoms.
First infusion: The recommended initial rate for infusion is 50 mg/h; after the first 30 minutes, it can be escalated in 50 mg/h increments every 30 minutes, to a maximum of 400 mg/h.
Subsequent infusions: All indications: Subsequent doses of rituximab can be infused at an initial rate of 100 mg/h, and increased by 100 mg/h increments at 30 minute intervals, to a maximum of 400 mg/h.
Rheumatoid arthritis only: Alternative subsequent, faster, infusion schedule: If patients did not experience a serious infusion related reaction with their first or subsequent infusions of a dose of 1,000 mg Rituximab 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/hour for the first 30 minutes and then 600 mg/hour for the next 90 minutes. If the more rapid infusion is tolerated, this infusion schedule can be used when administering subsequent infusions.
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.