Muromonab

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. 

Inhibition of immunomodulatory cytokines (Fig. 1) Anti-T-cell receptor antibodies Muromonab (OKT3, Orthoclone ) binds to the CD3 complex of the T-cell receptor and induces depletion of T-lymphocytes. It is applied to prevent acute rejection of kidney, liver, and heart allografts. Rapid side effects (within 30-60 min) include a cytokine release syndrome with fever, flu-like symptoms, and shock. Late side effects include an increased risk of viral and bacterial infections and an increased incidence of lymphproliferative diseases due to immunosuppression. 

Cytokines. Figure 1 Inhibition of cytokine synthesis during activation of the specific immune system. The monoclonal antibodies Muromonab and Basiliximab are specific for the CD3 complex of the T-cell receptor, and for the IL-2 receptor on lymphocytes, respectively. Cyclosporin and Tacrolimus inhibit activation of cytoplasmic NF-AT, a transcription factor essential for activation of the IL-2 gene ( NFAT Family of Transcription Factors). Sirolimus interferes with mTOR signaling and inhibits IL-2 dependent proliferation. Red pharmaka, blue target proteins. 

Treatment with specific antibodies (ALG, ATG, anti-CD3, anti-CD25) is indicated during the induction phase after transplantation and in the case of acute rejection for short time periods. Therapy with nonhuman antibodies may cause sensitization. Muromonab-CD3 might initiate a cytokine release syndrome (fever, chills, headache). 

Albumin, aminophylline, aspirin, heparin, insulin, metoclopramide, NSAIDs, muromonab-CD3 (OKT3), opiates, penicillins, propafenone, quinidine, senna, sulfonamide antimicrobials, and vancomycin... 

Orthoclone OKT3 Muromonab-GD3 Ortho Biotech, Bridgewater, NJ Anti-CD3 Transplants 1986... 

I. Interference with antigen recognition. Muromonab CDS is a monoclonal antibody directed against mouse CD-3 that blocks antigen recognition by T-lymphocytes (use in graft rejection). 

Montelukast Morphine hydrochloride Morphine sulfate Muromonab-CD3 Mycophenolate Mofetil... 

Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use muromonab-CD3. 

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. 

Cerebral edema - Cerebral edema and other signs of increased vascular permeability (eg, otitis media, nasal and ear stuffiness) have been seen in patients treated with muromonab-CD3 and may accompany some of the other neurologic manifestations. 

Infections Muromonab-CD3 is usually added to immunosuppressive therapeutic regimens, thereby augmenting the degree of immunosuppression. This increase in the total burden of immunosuppression may alter the spectrum of infections observed and increase the risk, the severity and the potential gravity (morbidity) of infectious complications. 

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. 

Drugs that may affect muromonab include indomethacin. 

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... 

Echinacea (Echinacea purpurea) Uses immune system stimulant prevention/Rx of colds, flu as supportive th apy for colds chronic infxns of the resp tract lower urinary tract Action Stimulates phagocytosis cytokine production T resp cellular activity topically exerts anesthetic, antimicrobial, anti-inflammatory effects Efficacy Not established may X severity duration of URI Available forms Caps w/ powdered herb equivalent to 300-500 mg, PO, tid pressed juice 6-9 mL, PO, once/d tine 2-4 mL, PO, tid (1 5 dilution) tea 2 tsp (4 g) of powdered herb in 1 cup of boiling water Noles/SE Fever, taste p -version, urticaria, angioedema Contra w/ autoimmune Dz, collagen Dz, progressive systemic Dz (TB, MS, collagen-vascular disorders), HIV, leukemia, may interfere w/ immunosuppressive therapy Interactions t Risk of disulfiram-like reaction W/ disulfiram, metronidazole T risk of exacerbation of HIV or AIDS W/ chinacea amprenavir, other protease inhibitors X effects OF azathioprine, basiliximab, corticosteroids, cyclosporine, daclizumab, econazole vag cream, muromonab-CD3, mycophenolate, prednisone, tacrolimus EMS Possible immunosuppression... 

Sgro, C. (1995) Side-effects of a monoclonal antibody, muromonab CD3/ orthoclone OKT3 bibliographic review. Toxicology, 105, 23-29. 

Muromonab (Orthoclone OKT3 ) is a mouse monoclonal antibody that kills T lymphocytes, cells that are a part of the immune response. Muromonab, the first monoclonal antibody approved for use as a drug, is used to treat rejection of a donated kidney, liver, or... 

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. 

Muromonab-(CD3) Orthoclone OKT3) is a mouse monoclonal antibody that is a purified IgG. It is used for the prevention of acute allograft rejection in kidney and hepatic transplants and as prophylaxis in cardiac transplantation. It is also used to deplete T cells in marrow from donors before bone marrow transplantation. 

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