What is the dosage and usage of Rituxan (rituximab)?

Rituxan (Rituximab) Dosage and Administration

Standard Dosing by Indication

For non-Hodgkin's lymphoma, the standard dose is rituximab 375 mg/m² administered intravenously once weekly for 4 weeks. 1, 2, 3

Non-Hodgkin's Lymphoma (NHL)

First-Line Treatment:

• 375 mg/m² IV weekly for 4 doses as monotherapy or in combination regimens (Category 1 recommendation) 1, 2
• Can be combined with bendamustine, RCHOP, or RCVP regimens 1
• For elderly or infirm patients unable to tolerate combination therapy, single-agent rituximab at 375 mg/m² weekly for 4 doses is the preferred option 1, 2

Maintenance Therapy:

• For high tumor burden: 375 mg/m² every 8 weeks for 12 doses (Category 1) 1, 2
• For patients initially treated with single-agent rituximab: 375 mg/m² every 8 weeks for 4 doses as consolidation 1, 2
• Second-line maintenance: 375 mg/m² every 12 weeks for 2 years (Category 1, optional) 1

Chronic Lymphocytic Leukemia (CLL)

• 375 mg/m² in cycle 1, then 500 mg/m² in cycles 2-6 in combination with fludarabine and cyclophosphamide (FC), administered every 28 days 3

Rheumatoid Arthritis (RA)

• Two 1,000 mg IV infusions separated by 2 weeks (one course) every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks 3
• Must be given in combination with methotrexate 3

ANCA-Associated Vasculitis (GPA/MPA)

Induction (Adults):

• 375 mg/m² once weekly for 4 weeks in combination with glucocorticoids 3

Follow-up (Adults):

• Two 500 mg IV infusions separated by 2 weeks, then 500 mg IV every 6 months thereafter based on clinical evaluation 3

Pediatric Dosing:

• Induction: 375 mg/m² once weekly for 4 weeks 3
• Follow-up: Two 250 mg/m² IV infusions separated by 2 weeks, then 250 mg/m² every 6 months 3

Pemphigus Vulgaris (PV)

• Two 1,000 mg IV infusions separated by 2 weeks in combination with tapering glucocorticoids 3
• Maintenance: 500 mg IV at month 12 and every 6 months thereafter 3
• Relapse treatment: 1,000 mg IV infusion, with subsequent infusions no sooner than 16 weeks after previous dose 3

Immune Thrombocytopenia (ITP)

• 375 mg/m² over 4 consecutive weekly infusions is the typical dosing, though lower doses may be sufficient 1
• Response rates vary significantly by patient population, with best results in adult females with newly diagnosed or persistent ITP (disease duration <1 year) when combined with high-dose dexamethasone 1

Administration Guidelines

Critical Safety Requirements:

• Must only be administered by a healthcare professional with appropriate medical support to manage severe infusion-related reactions 3
• Administer only as IV infusion; never as IV push or bolus 3
• Dilute to final concentration of 1-4 mg/mL in 0.9% sodium chloride or 5% dextrose 3

Mandatory Premedication

Standard Premedication (All Indications):

• Acetaminophen and antihistamine before each infusion 3

Additional Premedication for Specific Indications:

• RA, GPA/MPA, and PV patients: Methylprednisolone 100 mg IV (or equivalent) 30 minutes prior to each infusion 3
• Pediatric NHL patients: Prednisone as part of chemotherapy regimen prior to rituximab 3

Prophylactic Medications

Pneumocystis jirovecii Pneumonia (PCP) Prophylaxis:

• CLL patients: Required during treatment and for up to 12 months following treatment 3
• GPA/MPA patients: Required during treatment and for at least 6 months following last rituximab infusion 3
• PV patients: Should be considered during and following treatment 3
• Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred prophylactic agent, providing 91% reduction in PJP occurrence and 83% reduction in PJP-related mortality 4

Important Caveat: PCP prophylaxis is recommended regardless of concomitant steroid dose when rituximab is used for ANCA-associated vasculitis 4. The mechanism is B-cell depletion that persists for 6-12 months, making even standard therapeutic doses carry PCP risk 4.

Herpes Virus Prophylaxis:

• Recommended for CLL patients during and up to 12 months following treatment 3

Critical Monitoring Requirements

Pre-Treatment Screening:

• Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) testing is mandatory before initiating therapy 3
• Baseline immunoglobulin levels (IgG, IgM, IgA) 5
• Complete blood count with differential 5

During Treatment:

• IgG levels every 6 months in patients on rituximab 4
• Complete blood count at 2-4 month intervals 5
• Monitor for infusion reactions, particularly during first infusion 3

Post-Treatment:

• Tumor lysis syndrome prophylaxis should be considered in high-risk patients (those with high tumor burden) 1, 2

Storage and Preparation

• Diluted solutions may be stored refrigerated at 2°C to 8°C for 24 hours 3
• Stable for additional 24 hours at room temperature, though refrigeration preferred 3
• Discard any unused portion left in vial 3

Common Pitfalls to Avoid

Infusion-Related Reactions:

• 85-94% of patients experience adverse events, with 50-87% having flu-like symptoms during first infusion 6
• Most reactions occur within 30-120 minutes of first infusion 3
• Closely monitor patients with pre-existing cardiac/pulmonary conditions or high circulating malignant cell counts (≥25,000/mm³) 3
• If severe reaction occurs, temporarily discontinue and resume at minimum 50% reduction in rate after symptoms resolve 3

Hepatitis B Reactivation:

• Can occur in both HBsAg-positive and HBsAg-negative but anti-HBc-positive patients 3
• Reactivation can result in fulminant hepatitis, hepatic failure, and death 3
• Immunosuppressive effects may persist 1-2 years after last dose 4

Immunosuppression Duration:

• B-cell depletion persists for 6-12 months after treatment 4
• Do not discontinue PCP prophylaxis prematurely; continue minimum 6 months after last dose 4
• Low baseline IgG may predict higher risk of secondary immunodeficiency and justify prolonged prophylaxis 4

Progressive Multifocal Leukoencephalopathy (PML):

• Rare but potentially fatal complication reported with rituximab 1, 5
• Maintain high index of suspicion for neurological symptoms 5