Active Ingredient: Rituximab
Rituximab is indicated for the treatment of adult patients with CD20 positive diffuse large B cell non-Hodgkin’s lymphoma in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy.
Rituximab in combination with chemotherapy is indicated for the treatment of paediatric patients (aged ≥6 months to <18 years old) with previously untreated advanced stage CD20 positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL)/Burkitt leukaemia (mature B-cell acute leukaemia) (BAL) or Burkitt-like lymphoma (BLL).
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 375 milligrams rituximab per square meter of body surface, one dose. This step is repeated 8 times.
Premedication consisting of an anti-pyretic and an antihistaminic, e.g. paracetamol and diphenhydramine, should always be given before each administration of rituximab.
In adult patients with non-Hodgkin’s lymphoma, premedication with glucocorticoids should be considered if rituximab is not given in combination with glucocorticoid-containing chemotherapy.
Rituximab should be used in combination with CHOP chemotherapy. The recommended dosage 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.
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.
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. 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 (IRRs) usually respond to a reduction in the rate of infusion. The infusion rate may be increased upon improvement of symptoms.
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 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.
For:
In case that patient age in months is ≥ 6, intravenous, 375 milligrams rituximab per square meter of body surface, 6 doses in total.
In paediatric patients with non-Hodgkin’s lymphoma, premedication with paracetamol and H1 antihistamine (= diphenhydramine or equivalent) should be administered 30 to 60 minutes before the start of the infusion of rituximab. In addition, prednisone should be given as indicated in Table 1.
In paediatric patients from ≥6 months to <18 years of age with previously untreated, advanced stage CD20 positive DLBCL/BL/BAL/BLL, rituximab should be used in combination with systemic Lymphome Malin B (LMB) chemotherapy (see Tables 1 and 2). The recommended dosage of rituximab is 375 mg/m² BSA, administered as an intravenous infusion. No rituximab dose adjustments, other than by BSA, are required.
The safety and efficacy of rituximab paediatric patients ≥6 months to <18 years of age has not been established in indications other than previously untreated advanced stage CD20 positive DLBCL/BL/BAL/BLL. Only limited data are available for patients under 3 years of age.
Rituximab should not be used in paediatric patients from birth to <6 months of age with CD20 positive diffuse large B-cell lymphoma.
Table 1. Posology of rituximab administration for non-Hodgkin’s lymphoma paediatric patients:
| Cycle | Day of treatment | Administration details |
|---|---|---|
| Prephase (COP) | No rituximab given | - |
| Induction course 1 (COPDAM1) | Day -2 (corresponding to day 6 of the prephase) 1st rituximab infusion | During the 1st induction course, prednisone is given as part of the chemotherapy course, and should be administered prior to rituximab. |
| Day 1 2nd rituximab infusion | Rituximab will be given 48 hours after the first infusion of rituximab. | |
| Induction course 2 (COPDAM2) | Day -2 3rd rituximab infusion | In the 2nd induction course, prednisone is not given at the time of rituximab administration. |
| Day 1 4th e infusion | Rituximab will be given 48 hours after the third infusion of rituximab. | |
| Consolidation course 1 (CYM/CYVE) | Day 1 5th rituximab infusion | Prednisone is not given at the time of rituximab administration. |
| Consolidation course 2 (CYM/CYVE) | Day 1 6th rituximab infusion | Prednisone is not given at the time of rituximab administration. |
| Maintenance course 1 (M1) | Day 25 to 28 of consolidation course 2 (CYVE) No rituximab given | Starts when peripheral counts have recovered from consolidation course 2 (CYVE) with ANC> 1.0 × 109/l and platelets >100 × 109/l |
| Maintenance course 2 (M2) | Day 28 of maintenance course 1 (M1) No rituximab given | - |
ANC = Absolute Neutrophil Count; COP = Cyclophosphamide, Vincristine, Prednisone; COPDAM = Cyclophosphamide, Vincristine, Prednisolone, Doxorubicin, Methotrexate; CYM = CYtarabine (Aracytine, Ara-C), Methotrexate; CYVE = CYtarabine (Aracytine, Ara-C), VEposide (VP16)
Table 2. Treatment plan for non-Hodgkin’s lymphoma paediatric patients: concomitant chemotherapy with rituximab:
| Treatment plan | Patient staging | Administration details |
|---|---|---|
| Group B | Stage III with high LDH level (> N x 2), Stage IV CNS negative | Prephase followed by 4 courses: 2 induction courses (COPADM) with HDMTX 3g/m² and 2 consolidation courses (CYM) |
| Group C | Group C1: B-AL CNS negative, Stage IV & BAL CNS positive and CSF negative | Prephase followed by 6 courses: 2 induction courses (COPADM) with HDMTX 8g/m², 2 consolidation courses (CYVE) and 2 maintenance courses (M1 and M2) |
| Group C3: BAL CSF positive, Stage IV CSF positive |
Consecutive courses should be given as soon as blood count recovery and patient’s condition allows except for the maintenance courses which are given at 28 day intervals
BAL = Burkitt leukaemia (mature B-cell acute leukaemia); CSF = Cerebrospinal Fluid; CNS = Central Nervous System; HDMTX = High-dose Methotrexate; LDH = Lactic Acid Dehydrogenase
The recommended initial rate for infusion is 0.5 mg/kg/h (maximum 50 mg/h); it can be escalated by 0.5 mg/kg/h every 30 minutes if there is no hypersensitivity or infusion-related reactions, to a maximum of 400 mg/h.
Subsequent doses of rituximab can be infused at an initial rate of 1 mg/kg/h (maximum 50 mg/h); it can be increased by 1 mg/kg/h every 30 minutes to a maximum of 400 mg/h.
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