BENLYSTA® (belimumab) for injection

BENLYSTA is supplied as a sterile, white to off-white, preservative-free, lyophilized powder for intravenous infusion. Upon reconstitution with Sterile Water for Injection, USP, [see Dosage and Administration] each single-use vial delivers 80 mg/mL belimumab in 0.16 mg/mL citric acid, 0.4 mg/mL polysorbate 80, 2.7 mg/mL sodium citrate, and 80 mg/mL sucrose, with a pH of 6.5.

BENLYSTA ® (belimumab) is indicated for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy.

Limitations of Use
The efficacy of BENLYSTA has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. BENLYSTA has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of BENLYSTA is not recommended in these situations.

• Mortality: There were more deaths reported with BENLYSTA than with placebo during the controlled period of clinical trials.
• Serious Infections: Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including BENLYSTA. Use with caution in patients with chronic infections. Consider interrupting BENLYSTA therapy if patients develop a new infection during BENLYSTA treatment.
• Hypersensitivity Reactions, Including Anaphylaxis: Serious reactions have been reported. BENLYSTA should be administered by healthcare providers prepared to manage anaphylaxis. Monitor patients during and for an appropriate period of time after administration of BENLYSTA.
• Depression: Depression and suicidality have been reported in BENLYSTA studies. Patients should be instructed to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts or other mood changes.
• Immunization: Live vaccines should not be given concurrently with BENLYSTA.

To report SUSPECTED ADVERSE REACTIONS, contactHuman Genome Sciences, Inc. at 1-877-423-6597or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.

Dosage Schedule
BENLYSTA is for intravenous infusion only and must be reconstituted and diluted prior to administration. Do not administer as an intravenous push or bolus.

The recommended dosage regimen is 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter. Reconstitue, dilute and administer as an intravenous infusion only, over a period of 1 hour. The infusion rate may be slowed or interrupted if the patient develops an infusion reaction. The infusion must be discontinued immediately if the patient experiences a serious hypersensitivity reaction [see Contraindications, Warnings and Precautions].

Premedication Recommendations
Prior to dosing with BENLYSTA, consider administering premedication for prophylaxis against infusion reactions and hypersensitivity reactions.

Preparation of Solutions
BENLYSTA is provided as a lyophilized powder in a single-use vial for intravenous infusion only and should be reconstituted and diluted by a healthcare professional using aseptic technique as follows:

Reconstitution Instructions:

1. Remove BENLYSTA from the refrigerator and allow to stand 10 to 15 minutes for the vial to reach room temperature.
2. Reconstitute the BENLYSTA powder with Sterile Water for Injection, USP, as follows. The reconstituted solution will contain a concentration of 80 mg/mL belimumab.
   • Reconstitute the 120 mg vial with 1.5 mL Sterile Water for Injection, USP.
   • Reconstitute the 400 mg vial with 4.8 mL Sterile Water for Injection, USP.
3. The stream of sterile water should be directed toward the side of the vial to minimize foaming. Gently swirl the vial for 60 seconds. Allow the vial to sit at room temperature during reconstitution, gently swirling the vial for 60 seconds every 5 minutes until the powder is dissolved. Do not shake. Reconstitution is typically complete within 10 to 15 minutes after the sterile water has been added, but it may take up to 30 minutes. Protect the reconstituted solution from sunlight.
4. If a mechanical reconstitution device (swirler) is used to reconstitute BENLYSTA, it should not exceed 500 rpm and the vial swirled for no longer than 30 minutes.
5. Once reconstitution is complete, the solution should be opalescent and colorless to pale yellow, and without particles. Small air bubbles, however, are expected and acceptable. DilutionInstructions
6. Dextrose intravenous solutions are incompatible with BENLYSTA. BENLYSTA should only be diluted in 0.9% Sodium Chloride Injection, USP. Dilute the reconstituted product to 250 mL in 0.9% Sodium Chloride Injection, USP (normal saline) for intravenous infusion. From a 250-mL infusion bag or bottle of normal saline, withdraw and discard a volume equal to the volume of the reconstituted solution of BENLYSTA required for the patient’s dose. Then add the required volume of the reconstituted solution of BENLYSTA into the infusion bag or bottle. Gently invert the bag or bottle to mix the solution. Any unused solution in the vials must be discarded.
7. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard the solution if any particulate matter or discoloration is observed.
8. The reconstituted solution of BENLYSTA, if not used immediately, should be stored protected from direct sunlight and refrigerated at 2° to 8°C (36° to 46°F). Solutions of BENLYSTA diluted in normal saline may be stored at 2° to 8°C (36° to 46°F) or room temperature. The total time from reconstitution of BENLYSTA to completion of infusion should not exceed 8 hours.
9. No incompatibilities between BENLYSTA and polyvinylchloride or polyolefin bags have been observed.

Administration Instructions

1. The diluted solution of BENLYSTA should be administered by intravenous infusion only, over a period of 1 hour.
2. BENLYSTA should be administered by healthcare providers prepared to manage anaphylaxis.
3. BENLYSTA should not be infused concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of BENLYSTA with other agents.

Single-use vials of belimumab lyophilized powder for injection:
120 mg per vial
400 mg per vial

BENLYSTA is a sterile, preservative-free lyophilized powder for reconstitution, dilution, and intravenous infusion provided in single-use glass vials with a latex-free rubber stopper and a flip-off seal. Each 5-mL vial delivers 120 mg of belimumab. Each 20-mL vial delivers 400 mg of belimumab.

Store vials of BENLYSTA refrigerated between 2° to 8°C (36° to 46°F). Vials should be protected from light and stored in the original carton until use. Do not freeze. Avoid exposure to heat. Do not use beyond the expiration date.

Manufactured by:
Human Genome Sciences, Inc.
Rockville, Maryland 20850
US License No. 1820

Marketed by:
Human Genome Sciences, Inc.
Rockville, MD 20850
GlaxoSmithKline
Research Triangle Park, NC 27709
©2011, Human Genome Sciences, Inc. All rights reserved.