Daclizumab dosing

Recent data from a kidney pancreas induction study suggests that 2 doses of Daclizumab (2 mg/kg) at day 0 and day 14 is equivalent to 5 doses of 1 mg/kg every 14 days. (Stratta AJ, Alloway RR, Hodge E et al. A multicenter, open-label, comparative trial of two Daclizumab dosing strategies vs. no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids for the prevention of acute rejection in simultaneous kidney-pancreas transplant recipients interim analysis. Clin Transplant 2002 l6(l) 60-8.)... 

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... 

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

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. 

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. 

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. 

Pharmacokinetics In clinical trials, peak serum concentration (mean + SD) of daclizumab rose between the first dose (21... 

Daclizumab is used for the prophylaxis of acute rejection in patients receiving kidney transplants. A dose of 1 mg/kg is sufficient to completely block all the IL-2 receptors. It is administered in five doses at a 2-week interval where its elimination half-life is about 20 days. A combination of several other immunosuppressive agents including cyclosporine (or tacrolimus, rapamycin), mycophenolate mofetil and corticosteroids can be used with daclizumab. When it is used in combination with tacrolimus, the doses of tacrolimus are reduced. After tissue transplantation, the addition of daclizumab to the standard immunosuppressive regimen produces reduction in tissue rejection up to 50%. Daclizumab can cause hypersensitivity reactions, but it does not cause cytokine-release syndrome. There is a low incidence of... 

Zenapax Daclizumab Humanized IgGi CD25 Organ transplant IV 1 mg/kg Biweekly (5 doses)... 

A 42-year-old Hispanic woman, with end-stage renal disease, anemia, hypertension, and a history of an anaphylactic reaction to basiliximab, was scheduled to receive a living donor transplant and received basiliximab uneventfully (5). However, owing to donor infection the procedure was cancelled and rescheduled for 2 weeks later. Within 10 minutes after basiliximab reinduction she developed an anaphylactic reaction. In an attempt to find another induction therapy for this patient, skin testing was performed for daclizumab without response. She therefore received full-dose induction with daclizumab before her organ transplant without adverse effect. 

Of note, the anti-lL-2 Receptor (alpha chain) antibodies daclizumab and basilbdmab, widely studied in renal transplant recipients, did not induce cytokine release or first dose reactions [97]. 

M. Koch, G. Niemeyer, I. Patel, S. Light, and B. Nashan, Pharmacokinetics, pharmacodynamics, and immunodynamics of daclizumab in a two-dose regimen in liver transplantation. Transplantation 73(10) 1640-1646 (2002). 

Stratta RJ, Alloway RR, Lo A, Hodge E. Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients Primary endpoint analysis of a multicenter, randomized sffidy. Transplanation 2003 75 1260-1266. 

Eckhoff DE, McGuire G, Sellers M, et al. The safety and efficacy of a two-dose daclizumab (Zenapax) induction therapy in liver transplant recipients. Transplantation 2000 69 1867-1872. 

In a randomized, open, single-center study of two monoclonal antibodies to IL-2 receptors combined with triple immunosuppression (ciclosporin microemulsion, mycophenolate mofetil, and methylpredniso-lone), 212 adult recipients of at least 1HLA-mismatched dead donor renal graft were randomized to induction with basiliximab or daclizumab, given in standard doses. Hospital treatment was required in 50 and 59 patients with infections who received basiliximab and daclizumab respectively. There were one case of renal cell carcinoma and one of basal cell carcinoma in the basiliximab group, and one melanoma in the daclizumab group. There was one hypersensitivity reaction with daclizumab [119 ]. 

Skin One participant among six studied in a trial of high-dose daclizumab for the treatment of juvenile idiopathic arthritis-associated active anterior uveitis developed a rash possibly induced by daclizumab [216 =]. 

Yeh S, Wroblewski K, Buggage R, Li Z, Kurup SK, Sen HN, Dahr S, Sran P, Reed GF, Robinson R, Ragheb JA, Waldmann TA, Nussenblatt RB. High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active, non-infectious uveitis. J Auto-immun 2008 31(2) 91-7. 

Cardiovascular A patient continuing daclizumab therapy after evidence of a decrease in multiple sclerosis disease activity discontinued the treatment after 21 doses due to evidence of small-vessel CNS vasculitis [132 ]. 

---