Daclizumab

Humanized recombinant anti-IL-2 receptor antibodies (Basiliximab, Simulect , and Daclizumab Zenapax ). These antibodies bind with high affinity to the IL-2 receptor on T-lymphocytes and prevent activation and clonal expansion of anti-allograft T-lymphocytes by endogenous IL-2. They are used to prevent kidney allograft rejection. The main side effect is immunosuppression. 

Daclizumab Anti-IL-2 CD25 Allogeneic organ transplantation... 

Basiliximab and daclizumab are considered monoclonal antibodies. Daclizumab is a humanized antibody that is approximately 10% murine and 90% human, whereas basiliximab is a chimeric antibody that is approximately 30% murine and 70% human.9,11 These agents bind with high affinity to the IL-2 receptor, where they act as CD25 receptor antagonists. These receptors are present on almost all activated T cells. Their role in induction therapy involves inhibiting IL-2-mediated activation of lymphocytes, which is an important step for the clonal expansion of T cells. 

The Food and Drug Administration (FDA) approved dose of daclizumab is 1 mg/kg within 24 hours of transplant surgery and then 1 mg/kg administered every 2 weeks after surgery for a total of five doses.7,9,11 No dose adjustment is necessary in renal impairment, but no data are available for dose adjustments in hepatic dysfunction. Several trials have shown that a shorter dosing regimen of daclizumab, two doses given in a similar manner as basiliximab, may be as safe and effective as the full five-dose course.12,13... 

The most common adverse reaction with daclizumab is hyperglycemia, with clinical studies showing that a total of 32% of patients developed hyperglycemia.9,11 Most of the high glucose levels occurred the day after transplantation or in... 

Daclizumab (Zenapex ) 1 mg/kg IV x S doses Hyperglycemia (only after infusion) 6,907... 

Zenapax Daclizumab Hoffman-La Roche Prevention of kidney transplant rejection... 

Zenapax (Daclizumab, humanized Mab directed against the a chain of the IL-2 receptor)... 

Daclizumab Kidney transplant rejection (CD25), leukaemia... 

Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe daclizumab. The physician responsible for daclizumab administration should have complete information requisite for the follow-up of the patient. Daclizumab should only be administered by health care personnel trained in the administration of the drug who have available adequate laboratory and supportive medical resources. 

The recommended dose for daclizumab in adults and children is 1 mg/kg IV used as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids. Mix the calculated volume of daclizumab with 50 mL of sterile 0.9% sodium chloride solution, and administer via a peripheral or central vein over a 15-minute period. Not for direct injection. 

The standard course of daclizumab therapy is 5 doses. Give the first dose no more than 24 hours before transplantation. Give the 4 remaining doses at intervals of 14 days. 

Pharmacology Daclizumab is an immunosuppressive, humanized IgGI monoclonal antibody produced by recombinant DNA technology that binds specifically to the alpha subunit (Tac subunit) of the human high-affinity interleukin-2 (IL-2) receptor that is expressed on the surface of activated lymphocytes. Daclizumab is a composite of human (90%) and murine (10%) antibody sequences. 

The influence of body weight on systemic clearance supports the dosing of daclizumab on a mg/kg basis. For patients studied, this dosing maintained drug exposure within 30% of the reference exposure. 

Mortaiity The use of daclizumab as part of an immunosuppressive regimen including cyclosporine, mycophenolate mofetil, and corticosteroids may be associated with an increase in mortality. 

Lactation It is not known whether daclizumab is excreted in human milk. Because of the potential for adverse reactions, decide whether to discontinue nursing or... 

Immune system effects It is not known whether daclizumab use will have a long-term effect on the ability of the immune system to respond to antigens first encountered during daclizumab-induced immunosuppression. 

Readministration Readministration of daclizumab after an initial course of therapy has not been studied in humans. The potential risks of such readministration, specifically those associated with immunosuppression and/or the occurrence of anaphylaxis/anaphylactoid reactions, are not known. 

Immunogenicity Low titers of anti-idiotype antibodies to daclizumab were detected in the adult patients treated with daclizumab with an overall incidence of 14%. The incidence of anti-daclizumab antibodies observed in the pediatric patients was 34%. No antibodies that affected efficacy, safety, serum daclizumab levels or any other clinically related parameter were detected. 

Hyperglycemia - A total of 32% of daclizumab-treated patients (16% for placebo) had high fasting blood-glucose values. Most of these high values occurred either on the first day post-transplant when patients received high doses of corticosteroids or in patients with diabetes. 

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... 

Basiliximab is a chimeric mouse-human monoclonal antibody to the IL-2Ra receptor of T cells and daclizumab (Zenapax) is a humanized monoclonal antibody against the same receptor. They prevent binding of interleukin-2 to the CD25 antigen on activated T-lymphocytes thus inhibiting T-lymphocyte proliferation. Like the similar drug basiliximab, daclizumab reduces the incidence and severity of acute rejection in kidney transplantation without increasing the incidence of opportunistic infections. 

CD3 (muromonab-CD3), CD20 (Ritux-imab), CD25 (Basiliximab Daclizumab), CD33- (Gemtuzumab-ozogamicin), CD52 (Alemtuzumab)... 

Zenapax (Daclizumab) CD25 Humanized IgGi Allograft rejection 1997... 

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