What precautions and monitoring are necessary when administering rituximab (Rituxan) injection?

Precautions and Monitoring for Rituximab Administration

All patients receiving rituximab must be premedicated with an antipyretic (acetaminophen) and antihistamine (diphenhydramine) 30 minutes before each infusion, with strong consideration for adding methylprednisolone 100 mg IV (or equivalent) 30 minutes prior, especially for the first infusion. 1, 2

Pre-Treatment Screening Requirements

Before initiating rituximab therapy, the following screening is mandatory:

• Hepatitis B screening (HBsAg and anti-HBc) in all patients, as HBV reactivation can cause fulminant liver failure and death 3, 2
• Complete blood count (CBC) with differential and platelets 2
• Baseline immunoglobulin levels 3
• Tumor burden assessment to identify high-risk patients 1
• Latent tuberculosis screening 4

Critical Infusion-Related Reaction Risks

Rituximab carries a 77% incidence of infusion reactions during the first administration, decreasing to 3-8% in subsequent infusions 1, 5, 6. Severe reactions (grade 3-4) occur in approximately 10% of patients, with 80% of severe reactions happening during the first infusion 1.

Fatal infusion reactions have been reported, characterized by hypoxia, pulmonary infiltrates, respiratory distress, myocardial infarction, ventricular fibrillation, and cardiogenic shock 3, 7, 2.

Infusion Rate Protocol

First infusion:

• Start at 50 mg/hr 2
• In absence of toxicity, increase by 50 mg/hr increments every 30 minutes 2
• Maximum rate: 400 mg/hr 2
• Monitor vital signs continuously for at least 2 hours during infusion 1, 4

Subsequent infusions:

• Start at 100 mg/hr 2
• Increase by 100 mg/hr increments every 30 minutes to maximum 400 mg/hr 2

High-Risk Patients Requiring Special Precautions

Patients with high tumor burden or lymphocyte count >25 × 10⁹/L:

• Use reduced infusion rate for first infusion 1
• Consider split dosing over 2 days during first cycle 1, 4
• At increased risk for severe cytokine release syndrome 1, 3

Monitoring During and After Infusion

During infusion:

• Monitor vital signs regularly throughout 4
• Have emergency equipment immediately available (epinephrine, oxygen, IV fluids) 4
• Most reactions occur during infusion or within first 1-2 hours after completion 4, 7
• 95% of reactions manifest within 3 hours of infusion initiation 8

Post-infusion monitoring:

• Continue monitoring for 1-2 hours after infusion completion, particularly for first dose 4
• Patients can be safely managed in outpatient setting with appropriate monitoring 4

Management of Infusion Reactions by Grade

Grade 1 reactions (cutaneous symptoms only):

• Slow or temporarily stop infusion 2, 5
• Resume at half the previous rate after symptom resolution 2
• Same-day rechallenge is safe 3, 5

Grade 2 reactions (urticaria, nausea, vomiting, dyspnea, asymptomatic bronchospasm):

• Stop infusion and provide symptomatic treatment 7
• 84% of patients tolerate same-day rechallenge, though 16% may have recurrent grade 1-2 reactions 5
• Shared decision-making regarding rechallenge versus desensitization 3

Grade 3-4 reactions (symptomatic bronchospasm, hypoxia, anaphylaxis, hypotension):

• Stop infusion immediately 7
• Provide aggressive symptomatic treatment 7
• All patients with grade 3 reactions had recurrent reactions on same-day rechallenge 5
• Desensitization protocols required for future doses 3
• Permanently discontinue for grade 4 reactions 7

Infectious Complications and Prophylaxis

Mandatory prophylaxis:

• PCP prophylaxis for CLL patients during treatment and up to 12 months following 2
• PCP prophylaxis for GPA/MPA patients during treatment and at least 6 months after last infusion 2
• Consider PCP prophylaxis for pemphigus vulgaris patients 2
• Herpes virus prophylaxis for CLL patients 2

Hepatitis B management:

• If HBV positive, initiate preemptive antiviral therapy before rituximab 3
• Discontinue rituximab if HBV reactivation occurs 2

Progressive multifocal leukoencephalopathy (PML):

• Fatal JC polyomavirus encephalitis reported with increasing frequency 3
• No specific prophylaxis available; maintain high clinical suspicion 3

Ongoing Monitoring Schedule

For lymphoid malignancies:

• CBC with differential and platelets prior to each rituximab course during monotherapy 2
• Weekly to monthly CBC monitoring during rituximab plus chemotherapy 2

For RA, GPA, MPA:

• CBC with differential and platelets every 2-4 months during therapy 2
• Continue monitoring after final dose until cytopenias resolve 2

Immunoglobulin monitoring:

• Check serum immunoglobulin levels before and periodically after rituximab 3
• Hypogammaglobulinemia risk increases with multiple courses 3
• Antibody responses to recall antigens dramatically reduced, with median recovery time of 9 months (range 5.9-14.4 months) 3

Critical Pitfalls to Avoid

• Never administer rituximab as IV push or bolus - only as slow infusion 2
• Do not skip premedication, even for subsequent infusions 1, 2
• Do not assume patients with prior grade 3 reactions can be safely rechallenged without desensitization 5
• Patients who experienced IR at first treatment are 3.64 times more likely to have recurrent IR with subsequent treatments 8
• Corticosteroid premedication reduces severe reactions from 4.7% to 1% 1