Infusion reactions

ADCC. Cetuximab is approved for treatment of metastatic colorectal cancer (CRC) and squamous cell carcinoma of the head and neck (SCCHN). Interestingly, an adverse event, acneiform rash seems to correlate with a better response to cetuximab, while there is no such correlation with expression levels of EGFR assessed by immunohistochemistry. Further side effects are rare infusion reactions and hypomagnesia. Two other anti-EGFR antibodies approved for clinical use are the fully human antibody panitumumab (Vectibix)... 

Chills, fever, nausea, vomiting, headache, hypotension, hypertension, hypoxia, dyspnea, bone marrow depression Infusion reactions, hypotension, dizziness, anxiety, night sweats, rash, pruritus, nausea, diarrhea, vomiting, bone marrow depression... 

G, Mayer L, Plevy S The incidence and management of infusion reactions to infliximab a large centerexperience. AmJ Gastroenterol2003 98 1315-1324. 

N, nausea D, diarrhea HA, headache SOB, shortness of breath HTN, hypertension LFTs, liver function tests CBC, complete blood count ISR, injection-site reactions IR, infusion reactions IV, intravenous MYL, myelosuppression (watch for fever, symptoms of infection, easy bruisability, and bleeding) SC, subcutaneous. 

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. 

Liposomal doxorubicin Myelosuppression, palmar-plantar erythrodysesthesia (hand-foot syndrome) Alopecia, infusion reactions, stomatitis, fatigue, nausea, vomiting... 

Trastuzumab 4 mg/kg IV over 90 minutes on day 1 followed by 2 mg/kg over 90 minutes (30 minutes if no infusion-related reactions) once weekly or 8 mg/kg IV over 90 minutes on day 1 followed by 6 mg/kg IV over 90 minutes every 3 weeks Infusion reactions (fever, chills, rigors), nausea, vomiting, pain at tumor sites, headaches, dizziness, dyspnea, hypotension, heart failure... 

Alemtuzumab Infusion-reactions fever, chills, nausea, vomiting rash Antiviral and PCP prophylaxis should be initiated... 

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

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

Liposomal amphotericin B 3 mg/kg IV daily Lower incidence of nephrotoxicity and infusion reactions more expensive. 

Infliximab has been associated with infusion reactions, serum sickness, sepsis, and reactivation of latent tuberculosis. Adalimumab carries risks similar to infliximab. 

Infusion reactions Acute reactions including fever, shaking chills, hypotension. 

The majority of antibody-positive patients had low titers. Patients who were antibody-positive were more likely to have a higher rate of clearance, reduced efficacy and experience an infusion reaction. 

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. 

Infliximab intravenous infusions result in acute adverse infusion reactions in up to 10% of patients, but discontinuation of the infusion for severe reactions is required in less than 2%. Infusion reactions are more common with the second or subsequent infusions than with the first. Early mild reactions include fever, headache, dizziness, urticaria, or mild cardiopulmonary symptoms that include chest pain, dyspnea, or hemodynamic instability. Reactions to subsequent infusions may be reduced with prophylactic administration of acetaminophen, diphenhydramine, or corticosteroids. Severe acute reactions include significant hypotension, shortness of breath, muscle spasms, and chest discomfort such reactions may require treatment with oxygen, epinephrine, and corticosteroids. 

Anti-TNF antibodies, eg, infliximab, others Bind tumor necrosis factor and prevent it from binding to its receptors Suppression of several aspects of immune function, especially ThI lymphocytes Infliximab Moderately severe to severe Crohn s disease and ulcerative colitis others approved in Crohn s disease Infusion reactions reactivation of latent tuberculosis increased risk of dangerous systemic fungal and bacterial infections... 

Stealth liposomes Liposomal infusion reaction (hypoactivity, flushing, diarrhea, emesis, and decreased blood pressure seen following intravenous infusion in dogs) Transient effect (resolved within 1-2 hr). Biological significance is not apparent but the finding has been related to histamine release due to the infusion of a large amount of lipid 27... 

Infliximab is administered in combination with methotrexate for rheumatoid arthritis. A dose of 3 mg/kg is administered via intravenous infusion and is repeated after 2 and 6 weeks followed by the maintenance dose every 8 weeks. The recommended dose for Crohn s disease is 5 mg/kg. The side effects associated with the administration of infliximab include acute infusion reactions (fever, chills, chest pain, hypotension and rare anaphylaxis), increased risk of infection, production... 

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. 

Whether administered in combination or as a single therapy for cancers of the head, neck and colon, cetuximab exhibits similar pharmacokinetic characteristics. After a 2-h infusion of 400 mg/m2, the half-life is 97 h, ranging from 41 to 213 h, and after initial and subsequent maintenance doses, the half-life is about 112 h, ranging from 63 to 230 h. The adverse effects associated with cetuximab include immuno-genicity, electrolyte depletion (hypomagnesemia) and infusion reactions. Infusion reactions involve airway obstruction, urticaria and hypotension. 

An antibody directed at the murine epitope of infliximab may develop in patients. A delayed infusion reaction, which occurs 1-2 weeks after infusion, develops in approximately 5% patients who are re-treated with infliximab. Delayed infusion reaction is more common in patients with circulating anti-infliximab antibodies (20-30% of those getting multiple infusions) than in those without the antibodies. These reactions consist of myalgia arthralgia fever rash urticaria and facial, hand, and lip edema. Delayed reactions respond to symptomatic treatment with antihistamines or corticosteroids. Positive antinuclear antibodies (ANA) and anti-dsDNA develop in a small number of patients. Development of a lupus-like syndrome has been reported that resolved after discontinuation of the drug. 

Toxicities included an infusion reaction consisting of fever, chills, pain, asthenia, nausea, and vomiting. This syndrome was typically observed after the initial infusion, was self-limited, and frequently did not recur with subsequent infusions. The most serious toxicity was cardiac dysfunction, defined as clinical findings of congestive heart failure and/or subclinical declines in cardiac ejection fraction, which was seen in 5% of patients. Cardiotoxicity was unanticipated, as it had not been detected in previous studies. The mechanism for this effect is unclear, but is likely related to trastuzumab s antiproferative effect on HER2-mediated homeostasis and response to injury. 

Adverse effects Long-term use of infliximab is associated with development of anti-infliximab antibodies unless the drug is used in combination with methotrexate. Infusion reactions such as fever, chill, pruritus, or urticaria have occurred. Infections leading to pneumonia, cellulitis, and other conditions have also been reported. Whether treatment with infliximab predisposes to lymphoma, a condition that occurs with immunosuppressive or immune-altering drugs, remains to be established. 

Finally, it should be emphasized that drug-induced hypersensitivity reactions can be either immune mediated (e.g., anaphylaxis) or non-immune mediated [43], Infusion reactions associated with a number of therapeutic... 

Cheifetz A, Mayer L. Monoclonal antibodies, immunogenicity, and associated infusion reactions. Mount Sinai J Med 2005 72 250-6. 

In the clinical setting, infusion reactions occurred in many patients treated with agalsidase beta, and some of these reactions were severe. Infusion reactions occurred in some patients after receiving antipyretics, antihistamines, and oral steroids. 

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