What are the acute side effects of Rituximab (rituximab)?

Acute Side Effects of Rituximab

The most common acute side effects of rituximab include infusion-related reactions characterized by hypoxia, pulmonary infiltrates, respiratory distress, myocardial infarction, ventricular fibrillation, and cardiogenic shock, occurring primarily during the first infusion. 1, 2

Infusion-Related Reactions

Infusion-related reactions (IRRs) are the most prominent acute side effects of rituximab:

• Frequency: Occur in up to 77% of patients during first infusion 1, 3
• Timing: Typically occur within 30-120 minutes of starting the first infusion 2
• Severity: Most are mild to moderate, but approximately 10% can be severe 2, 4

Common IRR Symptoms

• Fever
• Chills/rigors
• Nausea
• Pruritus/urticaria/rash
• Hypotension or hypertension
• Angioedema
• Throat irritation
• Cough
• Bronchospasm
• Dyspnea/respiratory distress 1, 2

Severe IRR Manifestations

• Pulmonary infiltrates
• Acute respiratory distress syndrome
• Myocardial infarction
• Ventricular fibrillation
• Cardiogenic shock
• Fatal reactions (rare) 1, 2

Risk Factors for Severe Infusion Reactions

Patients at higher risk for severe IRRs include:

• Those with pre-existing cardiac or pulmonary conditions
• Those with prior cardiopulmonary adverse reactions
• Patients with high numbers of circulating malignant cells (≥25,000/mm³) 2
• Patients with hematologic malignancies (higher risk than those with autoimmune disorders) 5
• Specific combinations of: splenomegaly, history of allergy, low hemoglobin levels, and female gender 5

Other Acute Side Effects

1. Cytokine Release Syndrome:

   • Can occur within hours of infusion
   • Similar symptoms to allergic reactions but typically diminish with subsequent doses 1

2. Acute Mucocutaneous Reactions:

   • Can occur within the first day of exposure
   • Include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis 2

3. Serum Sickness:

   • Typically occurs 7-21 days after infusion
   • Characterized by fever, rash, and arthralgia
   • More common in pediatric patients with certain conditions 6

4. Acute Hematologic Effects:

   • Neutropenia
   • Thrombocytopenia
   • Leukopenia 2

Prevention and Management of Acute Side Effects

Premedication

• Standard premedication: Acetaminophen and an antihistamine before each infusion 2
• For certain conditions: Methylprednisolone 100 mg IV or equivalent 30 minutes prior to infusion 2
• Premedication with corticosteroids plus antihistamines reduces grade 3-4 reactions to approximately 1% 1

Administration Approach

• Start with a slow initial infusion rate, especially for first infusion 1, 2
• For patients with high tumor burden, consider:
  • Further reduced infusion rate for first infusion
  • Split dosing over 2 days during first cycle 1
• Monitor vital signs closely during infusion, particularly for first 2 hours 1

Management of IRRs

• For mild to moderate reactions: Temporarily slow or interrupt infusion
• For severe reactions: Discontinue infusion and provide supportive care
• Resume at minimum 50% reduction in rate after symptoms resolve 2
• Medical interventions may include:
  • Glucocorticoids
  • Epinephrine
  • Bronchodilators
  • Oxygen 2

Special Considerations

High-Risk Patients

• Patients with high tumor burden may benefit from:
  • More intensive monitoring
  • Slower infusion rates
  • Split dosing 1

Pediatric Patients

• Higher incidence of serum sickness in pediatric patients with ITP
• Infusion-related chills, fever, and respiratory symptoms occur in approximately 47% of children receiving first dose 1

Important Monitoring

• Monitor closely during first infusion and for 24 hours afterward
• Risk of reactions decreases with subsequent infusions 2, 7
• B-cell depletion typically occurs within 3-4 weeks after administration 3

Common Pitfalls and Caveats

1. Underestimating first infusion risk: The first infusion carries the highest risk of reactions; never rush it even if pressed for time.

2. Inadequate premedication: Failure to administer appropriate premedication can significantly increase risk of IRRs.

3. Missing early signs: Early symptoms of IRRs may be subtle; monitor patients closely for any changes in vital signs or new symptoms.

4. Confusing IRRs with other conditions: IRRs can mimic other conditions like serum sickness or even Kawasaki disease in rare cases 6.

5. Discontinuing treatment prematurely: Most patients can complete treatment after symptoms resolve with appropriate management.