What is the recommended dosage protocol for MABTHERA (Rituximab)?

Rituximab (MabThera) Dosage Protocol

The recommended dosage protocol for rituximab (MabThera) depends on the specific indication, with standard regimens being either 375 mg/m² administered intravenously once weekly for 4 weeks or 1000 mg administered on days 1 and 15. 1, 2

Standard Dosing Regimens by Indication

Non-Hodgkin's Lymphoma

• For non-Hodgkin's lymphoma, the standard dosage is 375 mg/m² administered intravenously once weekly for 4 weeks 2, 3
• For maintenance therapy in indolent NHL after initial treatment with high tumor burden, rituximab 375 mg/m² is given once every 8 weeks for 12 doses 2
• For elderly or infirm patients who cannot tolerate combination therapy, single-agent rituximab at 375 mg/m² weekly for 4 doses is recommended 2

ANCA-Associated Vasculitis (AAV)

• For induction of remission in AAV, rituximab 375 mg/m² is administered once weekly for 4 weeks 4, 5
• For maintenance therapy in AAV, two protocols are recommended:
  • 500 mg × 2 at complete remission, and 500 mg at months 6,12, and 18 thereafter (MAINRITSAN scheme) 4
  • 1000 mg infusion after induction of remission, and at months 4,8,12, and 16 after the first infusion (RITAZAREM scheme) 4

EBV-Related Post-Transplant Lymphoproliferative Disorders (PTLD)

• For preemptive therapy of EBV disease, rituximab 375 mg/m² is administered once weekly (1-4 doses) until EBV DNA-emia negativity 4
• For treatment of established EBV-PTLD, rituximab 375 mg/m² is given once weekly 4

Administration Guidelines

Premedication

• Premedication with antipyretic and antihistamine is recommended to reduce infusion reactions 6
• Infusion reactions occur in up to 77% of patients during the first infusion, requiring careful monitoring 6

Monitoring Requirements

• Baseline assessments before initiating therapy:
  • Immunoglobulin levels (IgG, IgM, IgA) 1
  • Hepatitis B and C antibody status 1
  • Latent tuberculosis screening 1, 6
• Complete blood count with differential should be monitored at baseline and at 2-4 month intervals during treatment 1, 6

Special Considerations

Dose Adjustments

• For patients receiving rituximab with cyclophosphamide for vasculitis, dose reductions may be needed:
  • For age 60 years: cyclophosphamide reduced to 12.5 mg/kg
  • For age 70 years: cyclophosphamide reduced to 10 mg/kg
  • For GFR <30 ml/min/1.73 m²: cyclophosphamide reduced by 2.5 mg/kg 4

Timing with Other Medications

• For patients with rheumatic diseases receiving rituximab, continuing other immunosuppressive medications around the time of vaccination is conditionally recommended 4
• For patients receiving rituximab, deferring non-live attenuated vaccinations (except influenza) until the next rituximab administration is due, and delaying rituximab for 2 weeks after vaccination, is conditionally recommended 4

Safety Considerations

• Major adverse events to monitor include:

  • Infusion-related reactions (typically during first infusion) 6, 7
  • Severe infectious complications in immunosuppressed patients 1
  • Progressive multifocal leukoencephalopathy 1
  • Hepatitis B reactivation 1, 2
  • Cytopenias 6, 7

• For Grade 1/2 infusion reactions, slow or temporarily stop the infusion and provide symptomatic treatment 6

• For Grade 3/4 reactions, stop the infusion and provide aggressive symptomatic treatment 6

Duration of Therapy

• For ANCA-associated vasculitis, the optimal duration of remission therapy is between 18 months and 4 years after induction of remission 4
• For maintenance therapy in lymphoma, duration depends on the specific protocol and response to treatment 2