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Daclizumab (Zenapax^®) (molecular wt = 144 kd.) is a humanized monoclonal antibody (IgG1) produced by recombinant DNA technology. It gained FDA approval in Dec 1997. It is known by several other names including HAT (Humanized Anti-Tac), SMART anti-Tac, anti-CD25, and humanized anti-IL2-receptor. It was developed and patented by Protein Design Laboratories (Mountain View, CA) and it is marketed by Hoffman LaRoche (Nutley, NJ ).

Daclizumab is a composite of human (90%) and murine (10%) antibody sequences. In the model below, the murine portions are shown in red and dark blue; the rest of the molecule (gray color) represents the human sequence

• Daclizumab binds specifically to the Tac subunit of the human high-affinity interleukin-2 (IL-2) receptor that is expressed on the surface of activated lymphocytes. It functions as an IL-2 receptor antagonist inhibiting IL-2-mediated stimulation of lymphocytes, a critical event in the process of allograft rejection.
• It is indicated for the prophylaxis of acute organ rejection in patients receiving renal transplants. It is used as part of an immunosuppressive regimen that may include cyclosporine (or tacrolimus?), mycophenolate, and corticosteroids. Patients receiving daclizumab may require lower levels (doses) of tacrolimus to maintain adequate overall level of immunosuppression.
• During the 1st 6 months post-transplant, the addition of daclizumab to the standard immunosuppressive regimen resulted in a ~50% reduction in the incidence of acute allograft rejection.
• Studies are ongoing to compare the efficacy and safety of daclizumab plus mycophenolate (double therapy) to the standard triple therapy (cyclosporine + mycophenolate + corticosteroids).

Pharmacokinetics

• A dose of 1 mg/kg is thought to maintain the trough level > 5 µg/mL and maintain the IL-2 receptors nearly completely saturated (blocked).
• The recommended 5-dose regimen maintains the IL-2 receptors saturated for up to 4 months after transplant.
• The terminal elimination half-life of daclizumab is similar to that of human IgG (~ 20 days)

Contraindications and Warnings

• Hypersensitivity reactions are possible. Premedication (with acetaminophen, diphenhydramine, and hydrocortisone) is recommended.
• Contraindicated in patients with previous history of serious hypersensitivity reaction to daclizumab.

Available As

25 mg / 5 mL vials, a clear, sterile colorless preservative-free buffered (phosphate, pH = 6.9) solution for injection. It must be further diluted before iv administration (see below).

Dose and Administration

• The recommended regimen consists of a total of 5 doses given at 2 weeks intervals. The 1st dose should be given within the 24 hrs preceding the transplant surgery.
• Each dose is 1 mg/kg diluted in 50 mL of normal saline and infused inravenously over 20 minutes. It may be administered via a peripheral or a central line.
• Pre-medication is recommended. For adults:
  • Hydrocortisone (Solu-Cortefâ) 100 mg IV X 1
  • Diphenhydramine (Benadrylâ) 50 mg PO or IV x1
  • Acetaminophen (Tylenol) 650 mg PO / PR
• Although there is no need for a test dose, medications for the treatment of severe hypersensitivity reactions should be available for immediate use.

Main Side Effects

• Data are still very limited. However, significant hypersensitivty reactions may occur.
• Addition of daclizumab did not increase the incidence of side effects, that are usually observed with the standard immunosuppressive regimen. However, cellulitis and wound infection occurred in 8.4% of patients receiving daclizumab compared to 4.1% of patients receiving placebo.

Drug Interactions

None documented

References

1. Carswell CI et al. Daclizumab: a review of its use in the management of organ transplantation. BioDrugs. 2001;15(11):745-73.
2. Billaud EM. Clinical pharmacology of immunosuppressive drugs: year 2000--time for alternatives. Therapie. 2000;55(1):177-83.
3. Ponticelli C, Tarantino A. Promising new agents in the prevention of transplant rejection. Drugs R D. 1999; 1(1):55-60.
4. Berard JL, Velez RL, Freeman RB, Tsunoda SM. A review of interleukin-2 receptor antagonists in solid organ transplantation. Pharmacotherapy. 1999 Oct;19(10):1127-37.
5. Eckhoff DE et al. The safety and efficacy of a two-dose daclizumab (zenapax) induction therapy in liver transplant recipients. Transplantation. 2000;69(9):1867-72.
6. Hirose R et al. Experience with daclizumab in liver transplantation: renal transplant dosing without calcineurin inhibitors is insufficient to prevent acute rejection in liver transplantation. Transplantation. 2000;69(2):307-11.
7. Wiseman LR et al. Daclizumab: a review of its use in the prevention of acute rejection in renal transplant recipients. Drugs. 1999;58(6):1029-42.