Antiinfectives

General Rx

Renal Rx

Transplant Rx

Pkinetics

Educational

KidneyWorks

Clinical Tools

Actions and Uses

Basiliximab (Simulect^®) (glycoprotein; mol. wt = 144 kd) is a chimeric (murine 40% /human 60%) monoclonal antibody (IgG1k) produced by recombinant DNA technology. It works by binding to the IL-2 receptor. It gained FDA approval in May 1998 and it is marketed by Novartis Pharmaceuticals Corporation (East Hanover, NJ).

• Basiliximab binds with high affinity and pecificity to the IL-2 receptor a-chain (IL-2Ra or CD25 antigen) on the surface of activated T-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?), and corticosteroids.
• During the 1st year post-transplant, the addition of basiliximab to the standard immunosuppressive regimen resulted in a ~30% reduction in the incidence of acute allograft rejection.

Pharmacokinetics

• Basiliximab's volume of distribution is about 9 L in adults and 5 L in children.
• The Total body clearance is 41 ± 19 mL/hr and terminal elimination half-life is 7 days.
• Clearance is not affected by body weight or gender. Also, among adult patients, elimination half-life is not influenced by gender, race, or age (20-69 years) .
• Compared to adults, children (2 - 15 yrs) have a lower clearance and a longer half-life (11.5 days).

Contraindications and Warnings

• Cases of significant hypersensitivity reactions have been reported.
• Contraindicated in patients who experienced a serious hypersensitivity reaction in the past.

Available As

Lyophilisate (powder) for injection. Each vial contains 20 mg of basiliximab to be reconstitued in 5 mL of sterile water for injection to yield a clear, sterile colorless preservative-free phosphate-buffered solution. This must be further diluted in 50 mL NS before iv administration (see below).

Dose and Administration

• Adults: The recommended regimen consists of two 20-mg doses given iv. The 1st dose should be given within 2 hrs prior to the transplant surgery. The second dose should be given 4 days after the transplant.
• Pediatric (2 - 15 years of age) protocol is similar to that for adults except that the recommended dose is 12 mg / m² BSA, up to a maximum of 20 mg.
• Each dose should be diluted in 50 mL of normal saline (or D5W) and infused inravenously over 20 minutes via a peripheral or a central line.
• The solution should not be shaken and should be used within a few hrs of reconstitution (it is stable for 4 hrs at room temperature and for 24 hrs when refrigerated) .
• Pre-medication is recommended. See administration protocol
• Although there is no need for a test dose, medications for the treatment of severe hypersensitivity reactions (e.g., epinephrine) should be available for immediate use.

Main Side Effects

• Data are still very limited.
• Addition of basiliximab did not increase the incidence of side effects, that are usually observed with the standard immunosuppressive regimen.

Drug Interactions

None documented

References

1. Billaud EM. Clinical pharmacology of immunosuppressive drugs: year 2000--time for alternatives. Therapie. 2000;55(1):177-83.
2. Ponticelli C, Tarantino A. Promising new agents in the prevention of transplant rejection. Drugs R D. 1999; 1(1):55-60.
3. Berard JL, Velez RL, Freeman RB, Tsunoda SM. A review of interleukin-2 receptor antagonists in solid organ transplantation. Pharmacotherapy. 1999;19(10):1127-37.
4. Onrust SV, Wiseman LR. Basiliximab. Drugs. 1999;57(2):207-13
5. Kirkman RL. New usage paradigms in antibody therapy: induction or true prophylaxis? Transplant Proc. 1999;31(1-2):1234-5.