Rituximab infusion reactions

Rituximab Infusion reactions fever, chills, rigors, Premedicate with acetaminophen, diphenhydramine,... 

Immunologic Rituximab is a frequent cause of infusion reactions, usually classified as cytokine release syndrome. Whether these reactions are in fact so-called cytokine release syndrome or true type I hypersensitivity responses is not always clear. In an investigation of immxme responses to the mAb in a rheumatoid arthritis patient who experienced two infusion reactions, the patient proved skin test-positive to the mAb and IgE anti-rituximab antibodies were found in the serum. The findings of rituximab-specific IgE antibodies and Th2 cells suggested type I hypersensitivity may be involved in at least some rituximab infusion reactions [195 ]. 

The exact role of rituximab in RA is not clearly defined, but it is indicated for patients with moderate to severe RA with a history of inadequate response to DMARDs and other BRMs. Rituximab carries a black-box warning of fatal infusion reactions and severe mucocutaneous reactions even though these events did not occur during the RA clinical trials. The benefits of rituximab must be tempered against the safety concerns reported with use of rituximab in the oncology setting. 

Watch for infusion reactions with rituximab and alemtuzumab. Premedicate with acetaminophen and diphenhydramine to prevent these reactions. 

Rituximab is given as two intravenous infusions of 1000 mg, separated by 2 weeks. It may be repeated every 6-9 months, as needed. Repeated courses remain effective. Pretreatment with glucocorticoids given intravenously 30 minutes prior to infusion (usually 100 mg of methylprednisolone) decreases the incidence and severity of infusion reactions. 

Most side effects are felt after the first treatment with rituximab and attention should be given to the rate of infusion. The most common immediate side effects of rituximab are fever, chills and respiratory symptoms, but these effects are much milder than the traditional chemotherapy. Other infusion reactions include nausea, angioedema, headache, hypotension, puritus, utricaria, rash and vomiting. The adverse effects decrease with each subsequent administration of the drug. Other side effects associated with rituximab include B-cell depletion, cytopenia, immuno-genicity and multiple pulmonary events. 

In addition to injection-site reactions, other mild to moderate reactions include fever, dizziness, sweating, and nausea. Low incidences of severe infusion reactions (e.g., hypotension, cardiac dysfunction, anaphylaxis, and bron-chospasms) have also been reported with Rituximab, Cetuximab, and even with humanized mAb Trastuzumab.46 Once again, the underlying mechanisms are poorly understood, limiting the application of mechanistic mathematical modeling for predicting infusion site reactions. 

Must consider toxicities of rituximab also, since always given in combination hematologic toxicity very delayed in onset, occurring 7 9 weeks after drug administration with 2 weeks for recovery infusion reactions asthenia, nausea, chills, fever tumor pain... 

Rituximab demonstrates dose-dependent pharmacokinetics. At a dose of375 mg/nf, the mean serum tj was 76 hours after one dose and 206 hours r er the last dose, with considerable interindividual variation. The wide range oftj likely reflects differences in patient tumor burden and normal B-cell populations. Rituximab toxicities are mostly related to infusion reactions, although there are increasing reports of late-onset neutropenia and rare reports of severe skin toxicity (Table 51-4). 

Rituximab CD20 Non-Hodgkins lymphoma Fever, infusion reactions, tumor lysis syndrome, infections, progressive multifocal leukoencephalopathy (PML)... 

Reactions following initial infusions of antibody are common, but these can usually be handled by a cautious rate of infusion, appropriate hydration and diuresis, and, if necessary, praned-ication. Twenty six percent of initial reactions are reported to be mild, 48 % moderate, and 26 % severe. The initial infusion reaction to some mAbs, for example, rituximab (see below), may provoke tumor lysis syndrome, cytokine release syndrome, and systemic inflammatory response syndrome. Tumor lysis syndrome, noted particularly with rituximab, can occur following cancer treatment and sometimes without treatment. It is believed to be the result of breakdown products of cancer cells leading to increased levels of some metabolites and reflected in conditions such as hypercalcemia, hyperkalemia, hyperphosphatemia, acute uric acid nephropathy, and acute renal failure. The syndrome can occur in the early stages of mAb therapy and is potentially life-threatening. Cytokine release syndrome, also called cytokine storm, is commonly seen after... 

As well as infnsion-related reactions and reactions related to the nnmber of circnlating target cells, a number of post-infusion hypersensitivity or hypersensitivity-like reactions occur to rituximab. These reactions inclnde sernm sickness, vasculitis, various cutaneous manifestations, interstitial pneumonitis, and aente respiratory... 

Initial infusion reaction to some mAbs, for example, rituximab, may provoke tumor lysis syndrome, cytokine release syndrome, and systemic inflammatory response syndrome. 

Systemic and cutaneous reactions have been reported following administration of infliximab. These include anaphylaxis, serum sickness, maculopapular rashes, urticaria, psoriasis, flare-up of atopic dermatitis, and leukocytoclastic vascuhtis. The overall incidence of infusion reactions in one study was 6.1 %. Mild, moderate, and severe reactions occurred in 3.1, 1.2, and 1 % of infliximab infusions, respectively. Patients with lymphocyte counts greater than 50 XIQP/L experienced a severe cytokine release syndrome shown by peaks in release of TNF and lL-6 90 min after infusion with rituximab. A number of post-infusion hypersensitivity or hypersensitivity-like reactions occur to rituximab. These reactions include serum sickness, vasculitis, various cutaneous manifestations, interstitial pneumonitis, and acute respiratory distress syndrome. 

Rituximab is a monoclonal antibody to the CD20 receptor expressed on the surface of B lymphocytes the presence of the antibody is determined during flow cytometry of the tumor cells. Cell death results from antibody-dependent cellular cytotoxicity. The pharmacokinetics of rituximab are best described by a two-compartment model, with a terminal half-life of 76 hours after the first infusion and a terminal half-life of 205 hours after the fourth dose.36 Rituximab has shown clinical activity in the treatment of B-cell lymphomas that are CD20+. Side effects include hypersensitivity reactions, hypotension, fevers, chills, rash, headache, and mild nausea and vomiting. 

A limitation of rituximab treatment is the severe and potentially fatal infusion-related reactions. To date, eight deaths have... 

About 30% of patients develop rashes with the first 1000 mg treatment this incidence decreases to about 10% with the second infusion and progressively decreases with each course of therapy thereafter. These rashes do not usually require discontinuation of therapy although urticarial or anaphylactoid reactions, of course, preclude further therapy. Immunoglobulins (particularly IgG and IgM) may decrease with repeated courses of therapy and infections can occur, although they do not seem directly associated with the decreases in immunoglobulins. Rituximab has not been associated with activation of tuberculosis, nor with the occurrence of lymphomas or other tumors (see Chapter 55). Other adverse effects, eg, cardiovascular events, are rare. 

Infnsion reactions with rituximab are generally well tolerated, as with most monoclonal antibodies. Most reactions are limited to the first infusion, including nansea, chills, and fever. They occur in over 90% of patients. More serious is the cytokine-release syndrome, which occnrs within 60-90 minutes and is characterized by fever, chills, rigors, bronchospasm, hypoxia, hypotension, nrticaria, and angioedema. Infusion must be discontinued, and the patient carefully monitored with chest radiography and fluid and electrolyte assessment and treated with oxygen and bronchodUators. 

In general, the MoAbs used in treating cancer are relatively well tolerated compared with conventional cytotoxic chemotherapy. The main adverse effect associated with rituximab use is infusion-related or hypersensitivity reactions. Patients may experience fever, rigors, dyspnea, hypotension, and rarely anaphylactoid reactions. Premedication with acetaminophen, diphenhydramine, and corticosteroids can reduce these reactions. Patients with significant tumor burden at the time of first treatment with rituximab may experience tumor lysis syndrome, and appropriate measures should be implemented to prevent this complication in these patients. 

Rituximab CD20 Normal and malignant B-lymphocytes B-cell NHL Hypersensitivity and infusion-related reactions... 

Rituximab is used against malignant B lymphocytes that express the CD20 antigen. The mean serum half-life is S9.8 hours, with variability possibly reflecting the tumor burden. Adverse reactions include hypersensitivity or anaphylactic reactions, cardiac arrhythmias, nausea, fatigue, and urticaria. Fever and chills may occur during infusion. 

Observational studies In a pooled analysis of data from patients with rheumatoid arthritis treated with rituximab in combination with methotrexate safety analyses were based on 5013 patient-years of rituximab exposure [146 ]. The most frequent adverse event was infusion-related reactions, which occurred in 25% of patients during the first infusion under 1% of infusion-related reactions were considered serious. The overall serious infection rate was 4.31 per 100 patient-years. Infections and serious infections remained stable over time across five courses. Compared with other patients with rheumatoid arthritis and with the general US population, there was no increased risk of malignancy. 

Rituximab and other chimeric antibodies (infusion-related reactions such as hypotension, cardiopulmonary reactions, angioedema mild to moderate infusion-related reactions such as fever, chills and rigors occur frequently). 

Immunologic The most common adverse drug reactions in patients receiving rituximab are infusion-related reactions, which occur during the first infusion in most cases... 

Human antichimeric antibodies develop in some patients after a first course of rituximab and can be associated with worsening of infusion or allergic reactions after subsequent infusions. In one case, there was failure to deplete B-cells after further courses [270"]. 

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