Rituximab (Nephrology)

Source: UK SPC (eMC) for Ituxredi 500 mg concentrate for solution for infusion, section 4.2 (https://www.medicines.org.uk/emc/product/101247/smpc). WHICH INDICATION THIS PAGE USES: the nephrology-relevant indication in this SPC is GPA/MPA (ANCA-associated vasculitis); the dose above is the ADULT INDUCTION regimen. ADULT MAINTENANCE (GPA/MPA): following induction of remission with rituximab, maintenance should be initiated no sooner than 16 weeks after the last rituximab infusion; following induction with other standard-of-care immunosuppressants, maintenance should be initiated during the 4 week period that follows disease remission. Give as two 500 mg IV infusions separated by two weeks, followed by a 500 mg IV infusion every 6 months thereafter. Patients should receive rituximab for at least 24 months after achievement of remission (absence of clinical signs and symptoms); for patients at higher risk of relapse, consider a longer duration of maintenance, up to 5 years. PREMEDICATION (all indications): an anti-pyretic and an antihistaminic (e.g. paracetamol and diphenhydramine) should always be given before each administration. For GPA/MPA specifically, 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. In adult GPA/MPA, methylprednisolone 1000 mg per day IV for 1 to 3 days is recommended prior to the first rituximab infusion (the last methylprednisolone dose may be given on the same day as the first rituximab infusion), followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day, tapered as rapidly as possible based on clinical need) 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, per local guidelines. PATIENT ALERT CARD must be given with each infusion in GPA/MPA (and in RA and pemphigus vulgaris). NO DOSE REDUCTIONS of rituximab are recommended; when given with chemotherapy, standard dose reductions apply to the chemotherapy agents only. CHECK THE FORMULATION: it is important to check the product labels to ensure the appropriate formulation (intravenous or subcutaneous) is being given as prescribed — this SPC is the INTRAVENOUS formulation. INFUSION RATE (adult and paediatric GPA/MPA, and adult NHL/CLL/RA/PV): first infusion — initial rate 50 mg/h, then escalate in 50 mg/h increments every 30 minutes to a maximum of 400 mg/h; subsequent infusions — initial rate 100 mg/h, increased by 100 mg/h increments at 30 minute intervals to a maximum of 400 mg/h. Mild or moderate infusion-related reactions usually respond to a reduction in infusion rate. 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 no more than one-half the previous rate. OTHER INDICATIONS IN THE SAME SPC (do NOT mix with the vasculitis regimen): follicular NHL combination induction 375 mg/m2 per cycle for up to 8 cycles on Day 1 of each chemotherapy cycle; follicular NHL maintenance 375 mg/m2 every 2 months (previously untreated, max 2 years / 12 infusions) or every 3 months (relapsed/refractory, max 2 years / 8 infusions); follicular NHL monotherapy 375 mg/m2 IV once weekly for four weeks; diffuse large B-cell NHL 375 mg/m2 on day 1 of each CHOP cycle for 8 cycles; CLL 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; rheumatoid arthritis 1000 mg IV followed by a second 1000 mg IV infusion two weeks later, need for further courses evaluated at 24 weeks; pemphigus vulgaris 1000 mg IV then a second 1000 mg IV two weeks later with tapering glucocorticoids, maintenance 500 mg IV at months 12 and 18 then every 6 months if needed, relapse 1000 mg IV with subsequent infusions no sooner than 16 weeks after the previous one. PAEDIATRIC (BSA-based, not per-kg, so paedDose is left null): for severe active GPA or MPA the recommended dose is 375 mg/m2 BSA IV once weekly for 4 weeks. Rituximab should NOT be used in paediatric patients less than 2 years of age with severe active GPA or MPA. Safety and efficacy in patients aged 2 to less than 18 years have not been established in indications other than severe active GPA or MPA. Paediatric GPA/MPA pre-treatment: methylprednisolone IV 30 mg/kg/day (not to exceed 1 g/day) for three daily doses before the first rituximab infusion, with up to three additional daily doses of 30 mg/kg IV possible, then oral prednisone 1 mg/kg/day (not to exceed 60 mg/day) tapered as rapidly as possible. Verify all paediatric dosing against a children's formulary. ELDERLY: no dose adjustment is required in patients aged over 65 years. RENAL IMPAIRMENT: section 4.2 of this SPC gives NO renal dose adjustment statement — despite this being a nephrology page, no renally-adjusted regimen is stated in the source, and none has been supplied here. SOURCE LIMITATIONS: eMC section 4.5 (interactions) was NOT captured in this bundle and no openFDA/US label was retrieved, so no interactions list is given below — check the SPC. Sections 4.4 and 4.8 were truncated at the fetch limit.