Basiliximab

Class Immunosuppressive chimeric monoclonal antibody, specifically binds to and blocks the interleukin-2 receptor alpha chain on the surface of activated T- lymphocytes 

Mechanism of Action Acts as an IL-2 receptor antagonist by binding with high affinity to the alpha chain of the IL-2 receptor complex and inhibits IL-2 binding Competitively inhibits IL-2 mediated activation of lymphocytes 

Indications Prophylaxis of acute renal allograft rejection when used as part of an immunosuppressive regimen that includes steroids and cyclosporine 

Warnings Should be administered in facilities equipped and staffed with adequate laboratory and supportive medical resources Administration of proteins may cause possible anaphylactoid reactions (none reported) Immunosuppressive therapies increase risk for lymphoproliferative disorders and opportunistic infections (incidence in basiliximab-treated patients is similar to placebo) 

Special Precautions Long-term effect and re-administration after initial course has not been studied Pregnancy Category B 

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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. 

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. 

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

Anticytokine receptor antibodies Basiliximab, Da-cluzimab Both are humanized monoclonal antibodies against the IL-2 receptor that block T-cell proliferation by inhibiting IL-2 and thus decrease the T-cell mediated frequency of rejection episodes in organ transplantation. 

The chimeric human/murine (basiliximab and dacluzi-mab) or murine (inolimomab) monoclonal antibodies are specifically directed against a part (CD25) of the interleukin-2 (IL-2) receptor. Binding of one of these antibodies to CD25 thereby displaces physiological IL-2 and prevents proliferation of activated T-lymphocytes. 

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 dose of basiliximab is 20 mg intravenously (IV) given within 2 hours prior to the transplant, followed by a second 20 mg dose on postoperative day 4.7,9,11 This dosing schedule can be used for both children weighing 35 kg (77 lb) or more and adults. Two 10 mg doses with the same dosing schedule should be used for children weighing less than 35 kg (77 lb). No specific dosage adjustments is needed in renal or hepatic impairment.7,9,11... 

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... 

Basiliximab (Simulect ) 20 mg IV x 2 doses None reported compared with 3,401... 

Simulect (Basiliximab, chimaeric Mab directed against the a chain of the IL-2 receptor)... 

The monoclonal antibodies daclizu-mab and basiliximab bind to the a-chain of the 11-2 receptor of T-lympho-cytes and thus prevent their activation, e.g., during transplant rejection. 

Basiliximab is a mouse/human chimeric monoclonal antibody with specificity and high affinity for the a-subunit of the IL-2 receptor. The antibody acts as an lL-2Ra antagonist and inhibits lL-2-mediated activation and proliferation of T l)unphocytes. It is indicated for the prevention of acute organ rejection in adult and paediatric renal transplant recipients in combination with other immunosuppressive agents like cyclosporin, azathioprine, mycophenolate mofetU... 

Azathioprine (Imuran) Basiliximab (Simulect) Cyclosporine, oral (Sandimmune, Neoral, Gengraf)... 

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... 

Lorber MI, Fastenau J, Wilson D, DiCesare J, Hall ML. A prospective economic evaluation of basiliximab (simulect) therapy following renal transplantation. Clin Transplant 2000 14 479-85. 

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)... 

Simulect (Basiliximab) CD25 Chimeric IgGi Allograft rejection 1998... 

B. Indications and use Basiliximab is indicated for the prophylaxis of acute organ rejection in patients receiving renal transplants. It is administered with an immunosuppressive regimen that includes cyclosporine and corticosteroids. 

Dosage form Simulect is a sterile lyophilized powder, packaged in glass vials. Each vial contains basiliximab 20 mg, to be reconstituted in sterile water for injection. 

Clinical pharmacology Basiliximab is a chimeric (mouse/human) interleukin-2 receptor antagonist. It is directed against the interleukin-2 receptor-alpha chain (CD25) on activated T-lymphocytes, and is a potent inhibitor of interleukin-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection. Another anti-CD25 monoclonal antibody, dacUzumab (Zenapax), has the same indication as basiliximab. 

Pharmacokinetics Complete and consistent blocking of the IL-2 receptor is maintained as long as serum basiliximab levels exceed 0.2pg/ml. As concentrations fall below this level, expression of IL-2 receptor returns to pre-therapy values within 1-2 weeks. Basiliximab has a steady-state volume of distribution of 9 liters and total body clearance of 41 ml/h. Its elimination half-life ranges from 7 to 10 days. There is a dose-proportional increase in peak concentration (Cmax) and area under the curve (AUC) up to the highest tested single dose of 60 mg. No clinically relevant influence of body weight or gender on distribution volume or clearance has been observed in adult patients. Elimination... 

Basiliximab, chimeric murine-human monoclonal IgGi against IL-2 receptor alpha... 

Renal Cyclosporine, azathioprine, prednisone, ALG, OKT3, tacrolimus, basiliximab,3 daclizumab,3 sirolimus Very good... 

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