Only physicians experienced in immunosuppressive therapy and management of solid organ transplant patients should use ORTHOCLONE OKT3 (muromonab-CD3). Patients treated with ORTHOCLONE OKT3 must be managed in a facility equipped and staffed for cardiopulmonary resuscitation and where the patient can be closely monitored for an appropriate period based on his or her health status.
Anaphylactic and anaphylactoid reactions may occur following administration of any dose or course of ORTHOCLONE OKT3. In addition, serious, occasionally life-threatening or lethal, systemic, cardiovascular, and central nervous system reactions have been reported following administration of ORTHOCLONE OKT3. These have included: pulmonary edema, especially in patients with volume overload; shock, cardiovascular collapse, cardiac or respiratory arrest, seizures, coma, cerebral edema, cerebral herniation, blindness, and paralysis. Fluid status should be carefully monitored prior to and during ORTHOCLONE OKT3 administration. Pretreatment with methylprednisolone is recommended to minimize symptoms of Cytokine Release Syndrome. (See: WARNINGS: Cytokine Release Syndrome, Central Nervous System Events, Anaphylactic Reactions; DOSAGE AND ADMINISTRATION).
ORTHOCLONE OKT3 (muromonab-CD3) Sterile Solution is a murine monoclonal antibody to the CD3 antigen of human T cells which functions as an immunosuppressant. It is for intravenous use only. The antibody is a biochemically purified IgG2a immunoglobulin with a heavy chain of approximately 50,000 daltons and a light chain of approximately 25,000 daltons. It is directed to a glycoprotein with a molecular weight of 20,000 in the human T cell surface which is essential for T cell functions. Because it is a monoclonal antibody preparation, ORTHOCLONE OKT3 Sterile Solution is a homogeneous, reproducible antibody product with consistent, measurable reactivity to human T cells.
Each 5 mL ampule of ORTHOCLONE OKT3 Sterile Solution contains 5 mg (1 mg/mL) of muromonab-CD3 in a clear colorless solution which may contain a few fine translucent protein particles. Each ampule contains a buffered solution (pH 7.0 ± 0.5) of monobasic sodium phosphate (2.25 mg), dibasic sodium phosphate (9.0 mg), sodium chloride (43 mg), and polysorbate 80 (1.0 mg) in water for injection.
The proper name, muromonab-CD3, is derived from the descriptive term murine monoclonal antibody. The CD3 designation identifies the specificity of the antibody as the Cell Differentiation (CD) cluster 3 defined by the First International Workshop on Human Leukocyte Differentiation Antigens.
ORTHOCLONE OKT3 is indicated for the treatment of acute allograft rejection in renal transplant patients.
ORTHOCLONE OKT3 is indicated for the treatment of steroid-resistant acute allograft rejection in cardiac and hepatic transplant patients.
The dosage of other immunosuppressive agents used in conjunction with ORTHOCLONE OKT3 should be reduced to the lowest level compatible with an effective therapeutic response. (See: WARNINGS and ADVERSE EVENTS: Infections, Neoplasia; DOSAGE AND ADMINISTRATION.)
Published Studies Related to Orthoclone Okt3 (Muromonab-CD3)
Cardiovascular side effects after renal allograft rejection therapy with Orthoclone: prevention with nitrendipine. 
Orthoclone (OKT-3), a monoclonal antibody, is an effective immunosuppressant in organ graft recipients... In group b (patients receiving 2 x 10 mg of nitrendipine before OKT-3 therapy was started and during the whole treatment course), in 3 of 13 patients, a short increase in blood pressure (13.7 +/- 2.9/7.8 +/- 5.1 mm Hg) was recorded 5 h after the first dose of OKT-3.(ABSTRACT TRUNCATED AT 250 WORDS).
Muromonab-CD3 for the successful treatment of early chronic rejection after pediatric liver transplantation: report of a case. [2011.04]
A four-and-a-half-year-old boy underwent living-donor liver transplantation (LDLT) for progressive familial intrahepatic cholestasis. Immunosuppressive therapy was commenced with tacrolimus and methylprednisolone, despite which derangement of liver function tests (LFTs) became evident on postoperative day (POD) 7.
Muromonab-CD3 therapy for refractory rejections after liver transplantation: a single-center experience during two decades in Japan. [2010.11]
BACKGROUND/PURPOSE: Refractory rejections still occur in the liver transplantation (LT) field. The aim of this study was to investigate significant factors for the introduction of therapy with muromonab-CD3 (MCD3) after LT... CONCLUSION: Optimal induction of MCD3 triggered recovery from refractory rejections, especially in LT recipients in a stable condition, but not in those in a critical or compromised condition.
[From orthoclone to denosumab, the fast growing market of monoclonal antibodies] [2009.12]
Monoclonal antibodies are a specific medicinal category within the current therapeutic armamentarium. Their market share is growing fast as they are often the only therapeutic option at some stages of certain diseases, due to their targeted action in the body and to an acceptable tolerance... The launch of biosimilars after patent expiry of some of these drugs will take time in view of the complexity of these molecules, and is not likely to significantly impact the cost of these therapies.
Muromonab-CD3 (Orthoclone OKT3), methylprednisolone and cyclosporine for acute graft-versus-host disease prophylaxis in allogeneic bone marrow transplantation. [2006.09]
We report the results of a prospective non-randomized phase II study of Muromonab-CD3 (Orthoclone OKT3), an anti-CD3 monoclonal antibody, with methylprednisolone (MP) and cyclosporine (CSA) for acute GVHD (aGVHD) prophylaxis in 22 hematologic malignancy patients... OKT3+MP+CSA combination is moderately effective aGVHD prophylaxis, however, it is unlikely to be superior to CSA+MTX.
Clinical Trials Related to Orthoclone Okt3 (Muromonab-CD3)
Oral OKT3 for the Treatment of Active Ulcerative Colitis [Active, not recruiting]
This study will assess the safety and efficacy of orally delivered short-term OKT3 in
patients with active ulcerative colitis.
Donor Peripheral Stem Cell Transplant and Donor Natural Killer Cell Transplant After Total-Body Irradiation, Thiotepa, Fludarabine, and Muromonab-CD3 in Treating Patients With Leukemia or Other Blood Diseases [Completed]
RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood
stem cell and donor natural killer cell transplant helps stop the growth of cancer and
abnormal cells and helps stop the patient's immune system from rejecting the donor's stem
cells. When certain stem cells from a donor are infused into the patient they may help the
patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
Sometimes the transplanted cells from a donor can make an immune response against the body's
normal cells. Removing the T cells from the donor cells before transplant may stop this from
PURPOSE: This phase II trial is studying how well giving a donor peripheral stem cell
transplant and a donor natural killer cell transplant after total-body irradiation,
thiotepa, fludarabine, and muromonab-CD3 works in treating patients with leukemia or other
Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies [Active, not recruiting]
Patients with refractory hematologic malignancies including those who develop recurrent
disease after allogeneic hematopoietic stem cell transplantation (HSCT) have a dismal
prognosis. Historically, both regimen-related mortality and disease recurrence have been
significant causes of treatment failure in this heavily pre-treated patient population. The
investigators institution has utilized mismatched family member donors for these patients
for several reasons: (1) Only 30% of patients have matched related donors available; (2)
transplantation can be performed more rapidly since the time to unrelated donor
trans-plantation averages 3 to 4 months; (3) the alloimmune reactivity of natural killer
(NK) cells following haploidentical HSCT has been shown to reduce relapse rates in certain
patient groups; and, (4) no other curative treatment options are available.
In the present trial, the investigators propose a novel conditioning regimen using
clofarabine in an effort to enhance cytotoxicity while simultaneously reducing regimen
related toxicity. In this phase I trial, the goal is to determine the maximum tolerated dose
(MTD) of clofarabine when used in combination with melphalan and thiotepa pre-transplant.
Study of Muromonab-CD3 and Cyclosporine in Patients With Giant Cell Myocarditis [Completed]
This is a study to determine the efficacy of muromonab-CD3 and cyclosporine as treatment in
patients with giant cell myocarditis (GCM). T lymphocytes appear to be involved in GCM.
Muromonab-CD3 has been shown to reduce the number of lymphocytes and cyclosporine inhibits
lymphocyte activation. This treatment may prolong patient survival until transplantation or
ventricular assist device placement is possible.
Phase II Randomized Study of Muromonab-CD3, Cyclosporine, Methylprednisolone, and Prednisone in Patients With Giant Cell Myocarditis [Completed]
I. Assess the effect of immunosuppression with muromonab-CD3, cyclosporine,
methylprednisolone, and prednisone versus standard care in terms of death, heart
transplantation, or left ventricular assistive device placement in patients with giant cell
II. Compare left ventricular ejection fraction prior to and after 4 weeks of treatment in
III. Compare the degree of myocardial inflammatory infiltrate prior to and after 4 weeks of
treatment in these arms.
Reports of Suspected Orthoclone Okt3 (Muromonab-CD3) Side Effects
Abdominal Pain (2),
Kidney Transplant Rejection (2),
Abdominal Tenderness (2),
Abdominal Discomfort (2),
Peritonitis Bacterial (2),
Epstein-Barr Virus Associated Lymphoproliferative Disorder (2),
Gastrointestinal Sounds Abnormal (2),
Renal Graft Loss (2),
Staphylococcal Skin Infection (2), more >>
Page last updated: 2011-12-09