HIGHLIGHTS OF PRESCRIBING INFORMATION −For Injection: 120 mg or 400 mg lyophilized powder in single-dose These highlights do not include all the information needed to use vials for reconstitution and dilution prior to intravenous infusion. (3) BENLYSTA safely and effectively. See full prescribing information for • Subcutaneous Injection BENLYSTA. −Injection: 200 mg/mL single-dose prefilled autoinjector or single-dose prefilled syringe. (3) BENLYSTA (belimumab) for injection, for intravenous use BENLYSTA (belimumab) injection, for subcutaneous use ------------------------------- CONTRAINDICATIONS ------------------------------ Initial U.S. Approval: 2011 Previous anaphylaxis to belimumab. (4) ----------------------------- RECENT MAJOR CHANGES --------------------------- ------------------------ WARNINGS AND PRECAUTIONS ----------------------- Indications and Usage (1) 12/2020 • Serious Infections: Serious and sometimes fatal infections have occurred Dosage and Administration (2.1, 2.2) 12/2020 in patients receiving immunosuppressive agents, including BENLYSTA. Warnings and Precautions, Mortality (5.1) Removed- Use with caution in patients with severe or chronic infections. Consider 09/2020 interrupting therapy with BENLYSTA if patients develop a new Warnings and Precautions, Serious Infections (5.1) 09/2020 infection during treatment with BENLYSTA. (5.1) Warnings and Precautions, Depression and Suicidality (5.4) 09/2020 • Progressive Multifocal Leukoencephalopathy (PML): Evaluate patients Warnings and Precautions, Concomitant Use with Other 12/2020 with new-onset or deteriorating neurological signs and symptoms for Biologic Therapies (5.7) PML. If confirmed, consider discontinuation of immunosuppressant therapy, including BENLYSTA. (5.1) ----------------------------- INDICATIONS AND USAGE ---------------------------- • Hypersensitivity Reactions, including Anaphylaxis: Serious and fatal BENLYSTA is a B-lymphocyte stimulator (BLyS)-specific inhibitor indicated reactions have been reported. BENLYSTA for intravenous use should be for the treatment of: administered by healthcare providers prepared to manage anaphylaxis. • patients aged 5 years and older with active, autoantibody-positive Monitor patients during infusion and for an appropriate period of time systemic lupus erythematosus (SLE) who are receiving standard therapy; after intravenous administration of BENLYSTA. (2.1, 5.2) (1) • Depression and Suicidality: Depression and suicidality have been • adult patients with active lupus nephritis who are receiving standard reported in trials with BENLYSTA. Assess for depression and risk of therapy. (1) suicide before treatment with BENLYSTA and monitor during • Limitations of Use: The efficacy of BENLYSTA has not been evaluated treatment. Instruct patients to contact their healthcare provider if new or in patients with severe active central nervous system lupus. BENLYSTA worsening depression, suicidal thoughts, or other mood changes occur. has not been studied in combination with other biologics. Use of (5.4) BENLYSTA is not recommended in these situations. (1) • Immunization: Live vaccines should not be given concurrently with BENLYSTA. (5.6) ------------------------- DOSAGE AND ADMINISTRATION ----------------------- • Intravenous Administration in Adults with SLE or Lupus Nephritis and ------------------------------- ADVERSE REACTIONS ------------------------------ Pediatric Patients with SLE • Common adverse reactions in adults (≥5%): nausea, diarrhea, pyrexia, −10 mg/kg at 2-week intervals for the first 3 doses and at 4-week nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, intervals thereafter. Reconstitute, dilute, and administer as an migraine, pharyngitis, and injection site reactions (subcutaneous intravenous infusion over a period of 1 hour. (2.1) administration). (6.1) −Consider administering premedication for prophylaxis against infusion • Adverse reactions in pediatric patients aged 5 years and older were reactions and hypersensitivity reactions. (2.1) consistent with those observed in adults. (6.2) • Subcutaneous Administration in Adults with SLE −200 mg once weekly. (2.2) To report SUSPECTED ADVERSE REACTIONS, contact • Subcutaneous Administration in Adults with Lupus Nephritis GlaxoSmithKline at 1-877-423-6597 or FDA at 1-800-FDA-1088 or −See Section 2.2. www.fda.gov/medwatch. ----------------------- DOSAGE FORMS AND STRENGTHS ---------------------- See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. • Intravenous Infusion Revised: 12/2020 FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 8.4 Pediatric Use 2 DOSAGE AND ADMINISTRATION 8.5 Geriatric Use 2.1 Intravenous Preparation and Dosing Instructions 8.6 Renal Impairment 2.2 Subcutaneous Dosing Instructions 8.7 Hepatic Impairment 3 DOSAGE FORMS AND STRENGTHS 8.8 Racial Groups 4 CONTRAINDICATIONS 10 OVERDOSAGE 5 WARNINGS AND PRECAUTIONS 11 DESCRIPTION 5.1 Serious Infections 12 CLINICAL PHARMACOLOGY 5.2 Hypersensitivity Reactions, including Anaphylaxis 12.1 Mechanism of Action 5.3 Infusion Reactions 12.2 Pharmacodynamics 5.4 Depression and Suicidality 12.3 Pharmacokinetics 5.5 Malignancy 13 NONCLINICAL TOXICOLOGY 5.6 Immunization 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.7 Concomitant Use with Other Biologic Therapies 14 CLINICAL STUDIES 6 ADVERSE REACTIONS 14.1 Clinical Trials with Intravenous Administration in Adults 6.1 Clinical Trials Experience with Intravenous Administration with SLE 6.2 Clinical Trials Experience with Subcutaneous 14.2 Clinical Trials with Intravenous Administration in Adults Administration in Adults with Lupus Nephritis 6.3 Postmarketing Experience 14.3 Clinical Trials with Intravenous Administration in Pediatric 6.4 Immunogenicity Patients with SLE 7 DRUG INTERACTIONS 14.4 Clinical Trials with Subcutaneous Administration in Adults 8 USE IN SPECIFIC POPULATIONS with SLE 8.1 Pregnancy 16 HOW SUPPLIED/STORAGE AND HANDLING 8.2 Lactation 16.1 Intravenous Infusion 8.3 Females and Males of Reproductive Potential 16.2 Subcutaneous Injection 1 Reference ID: 4718247 17 PATIENT COUNSELING INFORMATION *Sections or subsections omitted from the full prescribing information are not listed. FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE BENLYSTA (belimumab) is indicated for the treatment of: • patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy, and • adult patients with active lupus nephritis who are receiving standard therapy. Limitations of Use The efficacy of BENLYSTA has not been evaluated in patients with severe active central nervous system lupus. BENLYSTA has not been studied in combination with other biologics. Use of BENLYSTA is not recommended in these situations. 2 DOSAGE AND ADMINISTRATION BENLYSTA may be administered as an intravenous infusion in patients aged 5 years and older or as a subcutaneous injection in patients aged 18 years and older. Vials are intended for intravenous use only (not for subcutaneous use) and autoinjectors and prefilled syringes are intended for subcutaneous use only (not for intravenous use). 2.1 Intravenous Preparation and Dosing Instructions Recommended Intravenous Dosage Regimen — Adults with SLE or Lupus Nephritis and Pediatric Patients with SLE BENLYSTA for intravenous use must be reconstituted and diluted prior to administration. Do not administer as an intravenous push or bolus. The recommended intravenous dosage regimen is 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter. Reconstitute, dilute, and administer as an intravenous infusion 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 (4), Warnings and Precautions (5.2)]. Premedication Recommendations prior to Intravenous Use Prior to intravenous dosing with BENLYSTA, consider administering premedication for prophylaxis against infusion reactions and hypersensitivity reactions [see Warnings and Precautions (5.2, 5.3), Adverse Reactions (6.1)]. Preparation of Intravenous Solutions BENLYSTA for intravenous use is provided as a lyophilized powder in a single-dose vial and should be reconstituted and diluted by a healthcare professional using aseptic technique as 2 Reference ID: 4718247 follows. Use of a 21- to 25-gauge needle is recommended when piercing the vial stopper for reconstitution and dilution. Reconstitution Instructions for Intravenous Use: 1. Remove the vial of BENLYSTA from the refrigerator and allow to stand for 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.