Rituximab

MabThera should be administered under the close supervision of an experienced healthcare professional, in an environment where full resuscitation facilities are immediately available. Patients treated for RA, GPA/MPA or pemphigus vulgaris must be given the patient alert card with each infusion. PREMEDICATION - all indications: an anti-pyretic and an antihistaminic (e.g. paracetamol and diphenhydramine) should always be given before each administration. For RA, GPA, MPA and pemphigus vulgaris: premedication with 100 mg intravenous methylprednisolone should be completed 30 minutes prior to each infusion to decrease the incidence and severity of infusion-related reactions. GPA/MPA (adults) additionally: methylprednisolone given intravenously for 1 to 3 days at a dose of 1000 mg per day is recommended prior to the first MabThera infusion (the last methylprednisolone dose may be given on the same day as the first MabThera infusion), followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day, tapered as rapidly as possible) during and after the 4-week induction course. Pneumocystis jirovecii pneumonia prophylaxis is recommended for adult and paediatric GPA/MPA patients during and following treatment. MAINTENANCE TIMING (GPA/MPA): following induction with MabThera, maintenance should be initiated no sooner than 16 weeks after the last MabThera infusion; following induction with other standard-of-care immunosuppressants, maintenance should be initiated during the 4-week period that follows disease remission. RA ALTERNATIVE FASTER INFUSION: if a patient did not experience a serious infusion-related reaction with a 1000 mg dose given over the standard schedule, second and subsequent infusions may use the same concentration (4 mg/mL in a 250 mL volume) at 250 mg/hour for the first 30 minutes then 600 mg/hour for the next 90 minutes. Patients with clinically significant cardiovascular disease including arrhythmias, or previous serious infusion reactions to any prior biologic or to rituximab, should NOT be given the more rapid infusion. OTHER INDICATIONS in the same SPC (outside this page's primary rheumatology scope, quoted for completeness): follicular NHL combination induction 375 mg/m2 per cycle for up to 8 cycles; FL maintenance after response - previously untreated 375 mg/m2 every 2 months to a maximum of two years (12 infusions), relapsed/refractory 375 mg/m2 every 3 months to a maximum of two years (8 infusions); FL monotherapy (relapsed/refractory, stage III-IV chemoresistant or second or subsequent relapse) 375 mg/m2 once weekly for four weeks; adult DLBCL with CHOP 375 mg/m2 on Day 1 of each cycle for 8 cycles; CLL with chemotherapy 375 mg/m2 on Day 0 of the first cycle then 500 mg/m2 on Day 1 of each subsequent cycle for 6 cycles in total; pemphigus vulgaris 1000 mg then a second 1000 mg two weeks later with a tapering course of glucocorticoids, maintenance 500 mg at months 12 and 18 then every 6 months if needed, relapse 1000 mg with subsequent infusions no sooner than 16 weeks after the previous one. CLL prophylaxis: adequate hydration and uricostatics starting 48 hours prior to therapy to reduce tumour lysis risk; for CLL patients with lymphocyte counts above 25 x 10^9/L, prednisone/prednisolone 100 mg intravenous shortly before infusion is recommended. ELDERLY: no dose adjustment is required in patients aged 65 years and above. INFUSION REACTIONS: interrupt immediately for severe dyspnoea, bronchospasm or hypoxia; do not restart until complete resolution of symptoms and normalisation of laboratory values and chest X-ray, then resume at not more than one-half the previous rate. Mild or moderate infusion-related reactions usually respond to a reduction in infusion rate.

GPA/MPA (the paediatric indication relevant to this rheumatology page): the recommended dosage for induction of remission in paediatric patients with severe, active GPA or MPA is 375 mg/m2 body surface area, administered as an IV infusion once weekly for 4 weeks. Safety and efficacy in paediatric patients aged 2 to less than 18 years has NOT been established in indications other than severe, active GPA or MPA. MabThera should not be used in paediatric patients less than 2 years of age with severe, active GPA or MPA, because of the possibility of an inadequate immune response towards childhood vaccinations. Paediatric premedication for GPA/MPA: prior to the first IV infusion, methylprednisolone should be given IV for three daily doses of 30 mg/kg/day (not to exceed 1 g/day) to treat severe vasculitis symptoms; up to three additional daily doses of 30 mg/kg IV methylprednisolone can be given prior to the first MabThera infusion. Following completion of IV methylprednisolone, paediatric patients should receive oral prednisone 1 mg/kg/day (not to exceed 60 mg/day), tapered as rapidly as possible. NON-HODGKIN'S LYMPHOMA (outside this page's rheumatology scope): in paediatric patients from 6 months to less than 18 years with previously untreated, advanced stage CD20 positive DLBCL/BL/BAL/BLL, MabThera 375 mg/m2 BSA is given as an IV infusion in combination with systemic LMB chemotherapy on the schedule in SPC Tables 1 and 2 (six infusions across two induction and two consolidation courses); no dose adjustments other than by BSA are required. Only limited data are available for patients under 3 years of age. MabThera should not be used in paediatric patients from birth to 6 months of age with CD20 positive DLBCL. Paediatric NHL premedication: paracetamol and an H1 antihistamine (diphenhydramine or equivalent) 30 to 60 minutes before the start of the infusion, plus prednisone as indicated in SPC Table 1.