Muromonab adverse effects

Nonspecific immunosuppressive therapy in an adult patient is usually through cyclosporin (35), started intravenously at the time of transplantation, and given orally once feeding is tolerated. Typically, methylprednisone is started also at the time of transplantation, then reduced to a maintenance dose. A athioprine (31) may also be used in conjunction with the prednisone to achieve adequate immunosuppression. Whereas the objective of immunosuppression is to protect the transplant, general or excessive immunosuppression may lead to undesirable compHcations, eg, opportunistic infections and potential malignancies. These adverse effects could be avoided if selective immunosuppression could be achieved. Suspected rejection episodes are treated with intravenous corticosteroids. Steroid-resistant rejection may be treated with monoclonal antibodies (78,79) such as Muromonab-CD3, specific for the T3-receptor on human T-ceUs. Alternatively, antithymocyte globulin (ATG) may be used against both B- and T-ceUs. 

Muromonab is a mouse monoclonal antibody against the CD3 receptor of T-lymphocytes. Its activity is based on inhibition of interactions between antigen-presenting cells and T-cells. By preventing antigen presentation it suppresses T-cell activation and proliferation. The indication for muromonab is the treatment of acute graft rejection after kidney, liver and hart transplantations. Its adverse effects consist of those symptoms that are initiated by the release of cytokines and lymphokines as a result of the reaction of muromonab with CD3 positive T-lymphocytes. These symptoms may vary from a mild flu-like syndrome to serious cardiac, pulmonale and neurological reactions. 

Several anti-human T cell monoclonal antibodies have undergone preliminary trials in the treatment of renal allograft rejection. Most of these monoclonal antibodies were not effective than muromonab (1). T10B9, an antihuman pan-T lymphocyte monoclonal antibody, had similar efficacy but caused less fever, severe infection, respiratory, gastrointestinal, or neurological sjmptoms than muromonab (SEDA-22, 409). Other monoclonal antibodies, such as chimeric anti-CD7 and murine anti-ICAM-1 (CD54 enhmomab), were devoid of adverse effects or produced only minimal and transient adverse effects (SED-13,1134). 

A complex of acute systemic symptoms referred to as the cytokine-release syndrome is the most typical adverse effect of muromonab (3). A flu-like reaction is the key component of this complex syndrome, including fever, chills, headache, myalgia, tachycardia, and gastrointestinal symptoms. Other systemic and severe manifestations of the syndrome include acute pulmonary edema and... 

A study of patient records found that 4 out of a total of 55 kidney transplant patients (7.3%) given muromonab-CD3 and indometacin 50 mg orally or rectally every 6 to 8 hours for 48 to 72 hours developed serious encephalopathy and psychosis compared with only two out of 173 patients (1.2%) who had received muromonab-CD3 without indometacin. This appears to be an isolated report, and its general significance is unknown. Indometacin has been used to reduce the adverse effects of muromonab-CD3, and in one analysis concurrent use was associated with reduced fever, headache, and gastrointestinal disturbances. Muromonab-CD3 alone is associated with encephalopathy and other CNS adverse effects, and the manufacturer warns that patients should be closely monitored for these effects. ... 

---