Simulect (Page 3 of 3)

Malignancies

The incidence of malignancies in the controlled clinical trials of renal transplant was not significantly different between groups at 1 year (9/590 Simulect-treated patients vs. 12/594 placebo-treated patients) or among patients with 5-year follow-up from Studies 1 and 2 (21/295 Simulect-treated patients vs. 21/291 placebo-treated patients). The incidence of lymphoproliferative disease was not significantly different between groups, and less than 1% in the Simulect-treated patients.

Infections

The overall incidence of cytomegalovirus infection was similar in Simulect- and placebo-treated patients (15% vs. 17%) receiving a dual- or triple-immunosuppression regimen. However, in patients receiving a triple-immunosuppression regimen, the incidence of serious cytomegalovirus infection was higher in Simulect-treated patients compared to placebo-treated patients (11% vs. 5%). The rates of infections, serious infections, and infectious organisms were similar in the Simulect- and placebo-treatment groups among dual- and triple-therapy treated patients.

Postmarketing Experience

Severe acute hypersensitivity reactions, including anaphylaxis characterized by hypotension, tachycardia, cardiac failure, dyspnea, wheezing, bronchospasm, pulmonary edema, respiratory failure, urticaria, rash, pruritus, and/or sneezing, as well as capillary leak syndrome and cytokine release syndrome, have been reported during post-marketing experience with Simulect.

OVERDOSAGE

A 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.

DOSAGE AND ADMINISTRATION

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. Reconstituted 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 20 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.

Adults

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.

Pediatric

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

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. 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 50 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.

HOW SUPPLIED

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.

REFERENCES

1. Kahan, B.D., Rajagopalan P.R. and Hall M., Transplantation, 67, 276-284 (1999).
   
2. Nashan, B., Moore R., Amlot P., Schmidt A.-G., Abeywickrama K. and Soulillou J.-P., Lancet 350, 1193-1198 (1997).

Manufactured by:
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936

US License No. 1244

© Novartis

T2020-125

Revised: August 2020

PRINCIPAL DISPLAY PANEL

NOVARTIS NDC 0078-0393-61

Simulect^®
(basiliximab)
for injection

10 mg (single-dose vial)

FOR INTRAVENOUS ADMINISTRATION AFTER RECONSTITUTION.
Discard unused portion.

Rx only

PRINCIPAL DISPLAY PANEL

NOVARTIS NDC 0078-0331-84

Simulect^®
(basiliximab)
for injection

20 mg (single-dose vial)

FOR INTRAVENOUS ADMINISTRATION AFTER RECONSTITUTION.
Discard unused portion.

Rx only

SIMULECT basiliximab injection, powder, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0078-0393 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength BASILIXIMAB (BASILIXIMAB) BASILIXIMAB 10 mg in 2.5 mL

Inactive Ingredients Ingredient Name Strength SODIUM PHOSPHATE, DIBASIC, ANHYDROUS 0.50 mg in 2.5 mL GLYCINE 20 mg in 2.5 mL MANNITOL 41 mg in 2.5 mL POTASSIUM PHOSPHATE, MONOBASIC 3.66 mg in 2.5 mL SODIUM CHLORIDE 0.82 mg in 2.5 mL SUCROSE 10 mg in 2.5 mL

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:0078-0393-61 1 VIAL, SINGLE-USE in 1 CARTON contains a VIAL, SINGLE-USE 1 2.5 mL in 1 VIAL, SINGLE-USE This package is contained within the CARTON (0078-0393-61)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA103764 05/12/1998

SIMULECT basiliximab injection, powder, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0078-0331 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength BASILIXIMAB (BASILIXIMAB) BASILIXIMAB 20 mg in 5 mL

Inactive Ingredients Ingredient Name Strength SODIUM PHOSPHATE, DIBASIC, ANHYDROUS 0.99 mg in 5 mL GLYCINE 40 mg in 5 mL MANNITOL 80 mg in 5 mL POTASSIUM PHOSPHATE, MONOBASIC 7.22 mg in 5 mL SODIUM CHLORIDE 1.61 mg in 5 mL SUCROSE 20 mg in 5 mL

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:0078-0331-84 1 VIAL, SINGLE-USE in 1 CARTON contains a VIAL, SINGLE-USE 1 5 mL in 1 VIAL, SINGLE-USE This package is contained within the CARTON (0078-0331-84)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA103764 05/12/1998

Labeler — Novartis Pharmaceuticals Corporation (002147023)

Revised: 02/2021 Novartis Pharmaceuticals Corporation