SIMULECT

A recombinant chimeric (murine/human) monoclonal antibody (IgG1k) that functions as an immunosuppressive agent, specifically binding to and blocking the interleukin-2 receptor a-chain (IL-2R alpha, also known as CD25 antigen) on the surface of activated T-lymphocytes.

It is a 144 kDa glycoprotein obtained from fermentation of an established mouse myeloma cell line genetically engineered to express plasmids containing the human heavy and light chain constant region genes and mouse heavy and light chain variable region genes encoding the RFT5 antibody that binds selectively to the IL-2R alpha.

For prophylactic treatment of kidney transplant rejection

Basiliximab functions as an

IL-2 receptor antagonist.

Specifically it inhibits

IL-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection.

Most likely removed by opsonization via the reticuloendothelial system when bound to lymphocytes, or by human antimurine antibody production.

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maximum tolerated dose of Simulect ® (basiliximab) has not been determined in patients.

During the course of clinical studies, Simulect has been administered to adult renal transplantation patients in single doses of up to 60 mg, or in divided doses over 3-5 days of up to 120 mg, without any associated serious adverse events.

There has been one spontaneous report of a pediatric renal transplantation patient who received a single 20-mg dose (2.3 mg/kg) without adverse events.

Simulect ® (basiliximab) is contraindicated in patients with known hypersensitivity to basiliximab or any other component of the formulation.

See composition of Simulect under

Simulect ® (basiliximab) should be administered under qualified medical supervision.

Patients should be informed of the potential benefits of therapy and the risks associated with administration of immunosuppressive therapy.

While neither the incidence of lymphoproliferative disorders nor opportunistic infections was higher in Simulect-treated patients than in placebo-treated patients, patients on immunosuppressive therapy are at increased risk for developing these complications and should be monitored accordingly.

Severe acute (onset within 24 hours) hypersensitivity reactions, including anaphylaxis have been observed both on initial exposure to Simulect and/or following re-exposure after several months.

These reactions may include hypotension, tachycardia, cardiac failure, dyspnea, wheezing, bronchospasm, pulmonary edema, respiratory failure, urticaria, rash, pruritus, and/or sneezing.

Extreme caution should be exercised in all patients previously given Simulect when being administered a subsequent course of Simulect.

A subgroup of patients may be particularly at risk of developing severe hypersensitivity reactions on re-administration.

These are patients in whom concomitant immunosuppression was discontinued prematurely (e.g., due to abandoned transplantation or early loss of the graft) following the initial administration of Simulect.

If a severe hypersensitivity reaction occurs, therapy with Simulect should be permanently discontinued.

Medications for the treatment of severe hypersensitivity reactions, including anaphylaxis should be available for immediate use.

Simulect ® (basiliximab) is used as part of an immunosuppressive regimen that includes cyclosporine, USP (MODIFIED) and corticosteroids.

Simulect is for central or peripheral intravenous administration only.

Simulect should be given either as a bolus injection or diluted to a volume of 25 mL (10-mg vial) or 50 mL (20-mg vial) with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP and administered as an intravenous infusion over to 30 minutes.

Bolus administration may be associated with nausea, vomiting and local reactions, including pain.

Simulect should only be administered once it has been determined that the patient will receive the graft and concomitant immunosuppression.

Patients previously administered

Simulect should only be re-exposed to a subsequent course of therapy with extreme caution due to the potential risk of hypersensitivity See WARNINGS.

Parenteral drug products should be inspected visually for particulate matter and discoloration before administration.

After reconstitution, Simulect should be a clear-to-opalescent, colorless solution.

If particulate matter is present or the solution is colored, do not use.

Care must be taken to assure sterility of the prepared solution because the drug product does not contain any antimicrobial preservatives or bacteriostatic agents.

It is recommended that after reconstitution, the solution should be used immediately.

If not used immediately, it can be stored at 2ºC to 8ºC (36ºF to 46ºF) for 24 hours or at room temperature for 4 hours.

Discard the reconstituted solution if not used within 24 hours.

No incompatibility between

Simulect and polyvinyl chloride bags or infusion sets has been observed.

No data are available on the compatibility of Simulect with other intravenous substances.

Other drug substances should not be added or infused simultaneously through the same intravenous line.

In adult patients, the recommended regimen is two doses of 20 mg each.

The first 20-mg dose should be given within 2 hours prior to transplantation surgery.

The recommended second 20-mg dose should be given 4 days after transplantation.

The second dose should be withheld if complications, such as severe hypersensitivity reactions to Simulect or graft loss occur.

In pediatric patients weighing less than 35 kg, the recommended regimen is two doses of 10 mg each.

In pediatric patients weighing 35 kg or more, the recommended regimen is two doses of 20 mg each.

The first dose should be given within 2 hours prior to transplantation surgery.

The recommended second dose should be given 4 days after transplantation.

Reconstitution of 10 mg Simulect ® Vial To prepare the reconstituted solution, add 2.5 mL of Sterile Water for Injection, USP, using aseptic technique, to the vial containing the Simulect powder.

Shake the vial gently to dissolve the powder.

The reconstituted solution is isotonic and may be given either as a bolus injection or diluted to a volume of 25 mL with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP for infusion.

When mixing the solution, gently invert the bag in order to avoid foaming; DO NOT SHAKE.

Reconstitution of 20 mg Simulect ® Vial To prepare the reconstituted solution, add 5 mL of Sterile Water for Injection, USP, using aseptic technique, to the vial containing the Simulect powder.

The reconstituted solution is isotonic and may be given either as a bolus injection or diluted to a volume of 50 mL with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP for infusion.

Simulect ® (basiliximab) is supplied in a single-dose glass vial.

Each carton contains one of the following 1 Simulect 10 mg vial…………………………………………………….NDC 0078-0393-61 1 Simulect 20 mg vial…………………………………………………….NDC 0078-0331-84 Store lyophilized Simulect under refrigerated conditions at 2ºC to 8ºC (36ºF to 46ºF).

Do not use beyond the expiration date stamped on the vial.

It is not known whether

Simulect is excreted in human milk.

Because many drugs, including human antibodies are excreted in human milk, and because of the potential for adverse reactions, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

No randomized, placebo-controlled studies have been completed in pediatric patients.

In a safety and pharmacokinetic study, 41 pediatric patients (1-11 years of age [n = 27], 12-16 years of age [n = 14], median age 8.1 years) were treated with Simulect via intravenous bolus injection in addition to standard immunosuppressive agents, including cyclosporine, USP (MODIFIED), corticosteroids, azathioprine, and mycophenolate mofetil.

The acute rejection rate at 6 months was comparable to that in adults in the triple-therapy trials.

The most frequently reported adverse events were hypertension, hypertrichosis, and rhinitis (49% each), urinary tract infections (46%), and fever (39%).

Overall, the adverse event profile was consistent with general clinical experience in the pediatric renal transplantation population and with the profile in the controlled adult renal transplantation studies.

The available pharmacokinetic data in children and adolescents are described in CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.

It is not known whether the immune response to vaccines, infection, and other antigenic stimuli administered or encountered during Simulect therapy is impaired or whether such response will remain impaired after Simulect therapy.

Controlled clinical studies of

Simulect have included a small number of patients 65 years and older (Simulect 28; placebo 32).

From the available data comparing

Simulect and placebo-treated patients, the adverse event profile in patients ≥ 65 years of age is not different from patients < 65 years of age and no age-related dosing adjustment is required.

Caution must be used in giving immunosuppressive drugs to elderly patients.