Praxis Medical Insights

Introduction to Cardiac Events

Fatal infusion reactions can be characterized by hypoxia, pulmonary infiltrates, respiratory distress, myocardial infarction, ventricular fibrillation, and cardiogenic shock, according to the American College of Chest Physicians 1

Cardiogenic shock is a potential complication, as reported by the American College of Chest Physicians 1
Cardiac disorders, including myocardial infarction, arrhythmias, and shock, can occur, with a higher incidence in patients receiving rituximab with chemotherapy, as stated by the American College of Cardiology 2

Rituximab-related cardiac dysfunction is potentially reversible (Type II), unlike anthracycline-induced cardiotoxicity (Type I), as stated by the British Journal of Cancer, which may be affiliated with a relevant medical society 3

Infusion-related reactions are the most common adverse events associated with rituximab, occurring primarily during the first infusion, and can be severe or fatal, characterized by hypoxia, respiratory distress, pulmonary infiltrates, myocardial infarction, ventricular fibrillation, and cardiogenic shock, as reported by the American College of Chest Physicians 1
Patients developing cough and tachypnea during rituximab infusion are at risk of mast cell-mediated infusion reactions, which can rapidly progress to more severe symptoms including bronchospasm, hypoxia, and respiratory failure 2
The American College of Allergy, Asthma, and Immunology suggests checking oxygen saturation, respiratory rate, heart rate, blood pressure, and assessing for additional symptoms such as wheezing or bronchospasm, hypotension, angioedema, urticaria or flushing, and chest tightness in patients experiencing infusion reactions 2
Continue monitoring vital signs for at least 2 hours after symptoms resolve and observe for delayed or biphasic reactions 2

For mild to moderate reactions (Grade 1-2), the American Academy of Allergy, Asthma, and Immunology recommends oxygen supplementation as needed, diphenhydramine 25-50 mg IV, hydrocortisone 100 mg IV or methylprednisolone 80-125 mg IV, acetaminophen for fever if present, and albuterol nebulizer for bronchospasm 2
Premedication with corticosteroids plus antihistamines can reduce grade 3-4 reactions to approximately 1%, as stated by the American College of Allergy, Asthma, and Immunology 1
For severe reactions (Grade 3-4), the American College of Allergy, Asthma, and Immunology suggests all of the above plus epinephrine 0.3-0.5 mg IM (1:1000 solution) if hypotension or significant bronchospasm, consider additional doses of methylprednisolone 125 mg IV, IV fluids for hypotension, and may require intensive care monitoring 2

Patients at higher risk for severe infusion-related reactions include those with pre-existing cardiac or pulmonary conditions, prior cardiopulmonary adverse reactions, and high numbers of circulating malignant cells 4, 1
Pediatric patients with ITP may have a higher incidence of serum sickness, and infusion-related chills, fever, and respiratory symptoms occur in approximately 47% of children receiving the first dose, and monitor patients closely during the first infusion and for 24 hours afterward 1, 4

The American Academy of Allergy, Asthma, and Immunology recommends considering shared decision-making regarding rechallenge, and if rechallenge attempted, use 50% infusion rate under close monitoring 2
Consider desensitization protocol for future doses if rituximab is essential therapy, and enhanced premedication with H1 antihistamine, H2 antihistamine, acetaminophen, and methylprednisolone 100 mg IV 30 minutes prior to infusion 2
Desensitization protocol under specialist supervision, consider intermediate desensitization using a 3-bag, 12-step protocol or rapid desensitization using a 2-bag, 8-step protocol for severe reactions 2

Regular monitoring of B-cell counts and immunoglobulin levels is recommended, as well as monitoring for signs of infection, according to the American Society of Clinical Oncology 1
Screen for hepatitis B status before initiating therapy, as reactivation of occult hepatitis B infection has been reported in patients receiving rituximab 5, 6

Standard dosing for non-Hodgkin lymphomas is 375 mg/m² intravenously once weekly for 4 doses, and for follicular lymphoma maintenance, the dosing is 375 mg/m² one dose every 8 weeks for 12 doses 7
For patients initially treated with single-agent rituximab, consolidation with 375 mg/m² one dose every 8 weeks for 4 doses is recommended, and for ANCA-associated vasculitis maintenance, 500 mg every 6 months (FDA-approved) is recommended 7, 5, 6
Alternative maintenance regimens for ANCA-associated vasculitis include 1000 mg every 4 months or 1000 mg every 6 months 5

Rituximab causes profound B-cell depletion leading to increased infection risk, including bacterial, viral, and fungal infections, as stated by the Infectious Diseases Society of America 1
Neutropenia increases the risk of infection, particularly with long-term therapy or concurrent cytotoxic chemotherapy, according to the American Society of Clinical Oncology 1
Interstitial pneumonitis can occur in patients with non-Hodgkin's lymphoma, and may be fatal, but may respond to cessation of rituximab and steroid treatment, as reported by the American Thoracic Society 1
Hepatitis B reactivation can cause serious liver problems, including liver failure and death, and requires screening before treatment and monitoring during and after therapy, according to the American Association for the Study of Liver Diseases 1
Serum sickness can occur, particularly in pediatric patients with ITP, and presents with arthritis, fever, and cutaneous manifestations, according to the American Academy of Allergy, Asthma, and Immunology 1
Severe skin reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN), can occur, as reported by the American Academy of Dermatology 2