OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Muromonab-CD3 – Orthoclone OKT3®

DRUG CLASS

Transplant Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 28 December 2020

• Reuben A. Hepatotoxicity of immunosuppressive drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2011, pp. 569-91.

  (Review of hepatotoxicity of immunosuppressive agents mentions muromonab and problems of reactivation of hepatitis).
• Krensky AM, Azzi JR, Hafler DA. Immunosuppressants and toleragens. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 637-53.

  (Textbook of pharmacology and therapeutics).
• Ortho Multicenter Transplant Study Group. A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. N Engl J Med. 1985;313:337–42. [PubMed: 2861567]

  (Among 123 patients with acute rejection after renal transplantation, 94% of muromonab [OKT3] vs 75% of high dose methylprednisolone recipients had reversal of the acute rejection; adverse events included acute infusion reactions [fever, chills, tremor, dyspnea, chest tightness, wheezing and nausea], no mention of ALT elevations).
• Richards JM, Vogelzang NJ, Bluestone JA. Neurotoxicity after treatment with muromonab-CD3. N Engl J Med. 1990;323:487–8. [PubMed: 2115619]

  (Among 13 patients treated with muromonab for refractory solid tumors, 11 developed signs of neurotoxicity, some with culture negative cerebral spinal fluid pleocytosis, all resolving rapidly with symptomatic therapy).
• Swinnen LJ, Costanzo-Nordin MR, Fisher SG, O'Sullivan EJ, Johnson MR, Heroux AL, Dizikes GJ, et al. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. N Engl J Med. 1990;323:1723–8. [PubMed: 2100991]

  (Retrospective analysis found that 9 of 79 [9%] heart transplant recipients treated with muromonab vs 1 of 75 who did not receive muromonab developed posttransplant lymphoproliferative disorder).
• Claesson K, Tufveson G, Wahlberg J. Treatment with poly- and monoclonal antilymphocyte antibodies: assessment of efficacy and safety in transplantation. Transplant Proc. 1992;24:314. [PubMed: 1539293]

  (Among 145 patients undergoing organ transplantation, graft survival and adverse events were similar in those who received antibody therapy of rejection and those who did not; no mention of ALT elevations or hepatotoxicity).
• Norman DJ, Kahana L, Stuart FP Jr, Thistlethwaite JR, Shield CF 3rd, Monaco A, Dehlinger J, et al. A randomized clinical trial of induction therapy with OKT3 in kidney transplantation. Transplantation. 1993;55:44–50. [PubMed: 8420063]

  (Among 215 patients undergoing renal transplantation, use of muromonab as induction therapy was associated with fewer rejection episodes [51% vs 66%] and marginally improved graft-, but similar patient-survival; adverse events were more common with muromonab than conventional therapy, but were largely due to early infusion reactions [with fever, tachycardia, nausea and hypotension] and viral infections [herpes, CMV]; no mention of ALT elevations or hepatotoxicity).
• van Gelder T, Balk AH, Jonkman FA, Zietse R, Zondervan P, Hesse CJ, Vaessen LM, et al. A randomized trial comparing safety and efficacy of OKT3 and a monoclonal anti-interleukin-2 receptor antibody (BT563) in the prevention of acute rejection after heart transplantation. Transplantation. 1996;62:51–5. [PubMed: 8693545]

  (Among 60 patients undergoing heart transplantation randomized to receive either muromonab or a mouse monoclonal antibody to the IL2 receptor, infusion reactions were more common, and acute rejection episodes were delayed, but similar in frequency among the muromonab recipients; no mention of ALT elevations or hepatotoxicity).
• New monoclonal antibodies to prevent transplant rejection. Med Lett Drugs Ther. 1998;40(1036):93–4. [PubMed: 9774964]

  (Concise review of the efficacy and safety of basiliximab and daclizumab, two monoclonal antibodies to the IL2 receptor, shortly after their approval for use in transplantation in the US; mentions that muromonab has been used for many years for treatment of transplant rejection and is used with some success to prevent rejection; no mention of ALT elevations or hepatotoxicity).
• Midtvedt K, Fauchald P, Lien B, Hartmann A, Albrechtsen D, Bjerkely BL, Leivestad T, et al. Individualized T cell monitored administration of ATG versus OKT3 in steroid-resistant kidney graft rejection. Clin Transplant. 2003;17:69–74. [PubMed: 12588325]

  (Among 55 patients undergoing renal transplantation treated with variable doses of either ATG or muromonab based upon T cell counts, rejection rates were similar as were adverse events; no mention of ALT elevations or hepatotoxicity).
• Sellers MT, McGuire BM, Haustein SV, Bynon JS, Hunt SL, Eckhoff DE. Two-dose daclizumab induction therapy in 209 liver transplants: a single-center analysis. Transplantation. 2004;78:1212–7. [PubMed: 15502722]

  (Among 352 liver transplant recipients, the 209 who received daclizumab induction therapy had lower rates of acute rejection [25% vs 39%] and hepatitis C recurrent rates were similar; no mention of hepatotoxicity).
• Morris JA, Hanson JE, Steffen BJ, Chu AH, Chi-Burris KS, Gotz VP, Gordon RD. Daclizumab is associated with decreased rejection and improved patient survival in renal transplant recipients. Clin Transplant. 2005;19:340–5. [PubMed: 15877795]

  (Analysis of SRTR database on renal transplant recipients receiving daclizumab [n=8203] or no induction treatment [n=25368] in the US between 1998 and 2003 found lower reported rates of rejection [13% vs 17% after 3 years] and improved patient and graft survival, with no excess mortality from malignancy or opportunistic infections).
• Chin C, Pittson S, Luikart H, Bernstein D, Robbins R, Reitz B, Oyer P, et al. Induction therapy for pediatric and adult heart transplantation: comparison between OKT3 and daclizumab. Transplantation. 2005;80:477–81. [PubMed: 16123721]

  (Comparison of daclizumab [n=40] to muromonab [n=40] as induction therapy to prevent rejection after heart transplantation found no difference in rates of rejection, but higher rates of adverse events with muromonab including infections [33%], anaphylaxis [10%], and single cases of rejection death and acute renal failure [2%]; no mention of ALT elevations or hepatotoxicity).
• Segovia J, Rodríguez-Lambert JL, Crespo-Leiro MG, Almenar L, Roig E, Gómez-Sánchez MA, Lage E, et al. A randomized multicenter comparison of basiliximab and muromonab (OKT3) in heart transplantation: SIMCOR study. Transplantation. 2006;81:1542–8. [PubMed: 16770243]

  (Among 99 patients undergoing heart transplantation given therapy to prevent rejection with either basiliximab or muromonab, side effects were more common with muromonab and included fever [26%], pulmonary edema [10%], hypotension [8%], headache [4%], diarrhea, flushing, itching, confusion syndrome, nausea and vomiting; no mention of ALT elevations or hepatotoxicity).
• Cai J, Terasaki PI. Induction immunosuppression improves long-term graft and patient outcome in organ transplantation: an analysis of United Network for Organ Sharing registry data. Transplantation. 2010;90:1511–5. [PubMed: 21057388]

  (Since 2003, most solid organ transplant recipients have received induction therapy, and analyses of the UNOS registry for this period shows highest rates of patient and graft survival with alemtuzumab [89% 5 year patient survival] as compared to antithymocyte globulin [89%], basiliximab [84%], daclizumab [77%], steroids [75%] or no induction [71%]).
• Melis M, Biagi C, Småbrekke L, Nonino F, Buccellato E, Donati M, Vaccheri A, et al. Drug-induced progressive multifocal leukoencephalopathy: a comprehensive analysis of the WHO adverse drug reaction database. CNS Drugs. 2015;29:879–91. [PubMed: 26507833]

  (Among 2452 reports of progressive multifocal leukoencephalopathy submitted to the WHO Adverse Drug Database as of 2014, 343 different drugs were implicated, most commonly natalizumab [n=618], rituximab [519], methotrexate [244], cyclophosphamide [215], fludarabine [152], vincristine [125], prednisone [110] and mycophenolic acid [109], but also muromonab [12], basiliximab [4] and antithymocyte globulin [10]).