Muromonab dosing

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. 

Anaphylactic or anaphylactoid reactions may occur following administration of any dose or course of muromonab-CD3. Serious and occasionally life-threatening systemic, cardiovascular, and CNS reactions have been reported. These have included the following Pulmonary edema, especially in patients with volume overload shock cardiovascular collapse cardiac or respiratory arrest seizures coma. Hence, a patient being treated with muromonab-CD3 must be managed in a facility equipped and staffed for cardiopulmonary resuscitation. 

Monitor Monitor patients closely for the first few doses. Methylprednisolone sodium succinate 8 mg/kg IV given 1 to 4 hours prior to muromonab-CD3 administration is strongly recommended to decrease the incidence of reactions to the first dose. Acetaminophen and antihistamines, given concomitantly, may reduce early reactions. Patient temperature should not exceed 37.8°C (100°F) prior to first administration. 

Cytokine release syndrome (CRS) Temporally associated with the administration of the first few doses of muromonab-CD3 (particularly, the first 2 to 3 doses), most P.1174... 

Prevention/Minimization - Manifestations of the CRS may be prevented or minimized by pretreatment with 8 mg/kg methylprednisolone, given 1 to 4 hours prior to administration of the first dose of muromonab-CD3 and by closely following recommendations for dosage and treatment duration. 

Neuropsychiatric events Seizures, encephalopathy, cerebral edema, aseptic meningitis, and headaches have occurred during therapy with muromonab-CD3, even following the first dose, resulting in part from T-cell activation and subsequent systemic release of cytokines. 

Lactation It is not known whether muromonab-CD3 is excreted in breast milk. Children Safety and efficacy in children have not been established. Muromonab-CD3 has been used in infants/children, beginning with a dose of 5 mg or less. 

Muromonab-CD3 (Orthoclone OKT3) [Immunosuppressant/ Monoclonal Antibody] WARNING Can cause anaphylaxis monitor fluid status Uses Acute rejection following organ transplantation Action Murine Ab, blocks T-cell Fxn Dose Per protocol Adults. 5 mg/d IV for 10-14 d Peds. 0.1 mg/kg/d IV for 10-14 d Caution [C, /-] w/ Hx Szs, PRG, uncontrolled HTN Contra Murine sensitivity, fluid overload Disp Inj SE Anaphylaxis, pulm edema, fever/chills w/ 1st dose (premedicate w/ stCToid/APAP/antihistamine) Interactions t Effects W/ immunosuppressives t effects OF live virus vaccines t risk of CNS effects encephalopathy W/ indomethacin EMS Monitor for S/Sxs of Infxn monitor resp Fxn, known to... 

If CD3 levels remain high during therapy with muromonab-CD3, the dose may be increased or one may switch to an alternate antilymphocyte preparation. 

Therapeutic Uses Muromonab-CD3 is indicated for treatment of acute organ transplant rejection. The recommended dose is 5 mg/day (in adults less for children) in a single intravenous bolus (<1 minute) for 10-14 days. Antibody levels increase over the first 3 days and then plateau. Circulating T cells disappear from the blood within minutes of administration and return within 1 week after cessation of therapy. Repeated use of muromonab-CD3 results in the immunization of the patient against the mouse determinants of the antibody, which can neutralize and prevent its immunosuppressive efficacy. Thus, repeated treatment with the muromonab-CD3 or other mouse monoclonal antibodies generally is contraindicated. 

Glucocorticoid administration before the injection of muromonab-CD3 considerably reduces first-dose reactions and is now standard. Volume status of patients also must be monitored carefully before therapy steroids and other premedications should be given, and a fully competent resuscitation facility must be immediately available for patients receiving their first several doses. 

Muromonab-CD3 This MAb binds to the CDS antigen on the surface of human thymocytes and mature T cells. It blocks the killing action of cytotoxic T cells and probably interferes with other T cell functions. Muromonab-CD3 is used to manage a renal homograft rejection crisis. First-dose effects include fever, chills, dyspnea, and pulmonary edema. Hypersensitivity reactions may also occur. 

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