HIGHLIGHTS OF PRESCRIBING INFORMATION • Subcutaneous Injection These highlights do not include all the information needed to use −Injection: 200 mg/mL single-dose prefilled autoinjector or single-dose BENLYSTA safely and effectively. See full prescribing information for prefilled syringe. (3) BENLYSTA. ----------------------------------- CONTRAINDICATIONS --------------------------------- BENLYSTA (belimumab) for injection, for intravenous use Previous anaphylaxis to belimumab. (4) BENLYSTA (belimumab) injection, for subcutaneous use Initial U.S. Approval: 2011 --------------------------- WARNINGS AND PRECAUTIONS -------------------------- • Serious Infections: Serious and sometimes fatal infections have occurred ------------------------------- RECENT MAJOR CHANGES------------------------------ in patients receiving immunosuppressive agents, including BENLYSTA. Indications and Usage (1) 12/2020 Use with caution in patients with severe or chronic infections. Consider Dosage and Administration (2.1, 2.2) 12/2020 interrupting therapy with BENLYSTA if patients develop a new Warnings and Precautions, Mortality (5.1) Removed- infection during treatment with BENLYSTA. (5.1) 09/2020 • Progressive Multifocal Leukoencephalopathy (PML): Evaluate patients Warnings and Precautions, Serious Infections (5.1) 09/2020 with new-onset or deteriorating neurological signs and symptoms for Warnings and Precautions, Depression and Suicidality (5.4) 09/2020 PML. If confirmed, consider discontinuation of immunosuppressant Warnings and Precautions, Concomitant Use with Other 12/2020 therapy, including BENLYSTA. (5.1) Biologic Therapies (5.7) • Hypersensitivity Reactions, including Anaphylaxis: Serious and fatal reactions have been reported. BENLYSTA for intravenous use should be -------------------------------- INDICATIONS AND USAGE ------------------------------ administered by healthcare providers prepared to manage anaphylaxis. BENLYSTA is a B-lymphocyte stimulator (BLyS)-specific inhibitor indicated Monitor patients during infusion and for an appropriate period of time for the treatment of: after intravenous administration of BENLYSTA. (2.1, 5.2) • patients aged 5 years and older with active, autoantibody-positive • Depression and Suicidality: Depression and suicidality have been systemic lupus erythematosus (SLE) who are receiving standard therapy; reported in trials with BENLYSTA. Assess for depression and risk of (1) suicide before treatment with BENLYSTA and monitor during • adult patients with active lupus nephritis who are receiving standard treatment. Instruct patients to contact their healthcare provider if new or therapy. (1) worsening depression, suicidal thoughts, or other mood changes occur. • Limitations of Use: The efficacy of BENLYSTA has not been evaluated (5.4) in patients with severe active central nervous system lupus. BENLYSTA • Immunization: Live vaccines should not be given concurrently with has not been studied in combination with other biologics. Use of BENLYSTA. (5.6) BENLYSTA is not recommended in these situations. (1) ----------------------------------- ADVERSE REACTIONS---------------------------------- ---------------------------DOSAGE AND ADMINISTRATION ------------------------- • Common adverse reactions in adults (≥5%): nausea, diarrhea, pyrexia, • Intravenous Administration in Adults with SLE or Lupus Nephritis and nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, Pediatric Patients with SLE migraine, pharyngitis, and injection site reactions (subcutaneous −10 mg/kg at 2-week intervals for the first 3 doses and at 4-week administration). (6.1) intervals thereafter. Reconstitute, dilute, and administer as an • Adverse reactions in pediatric patients aged 5 years and older were intravenous infusion over a period of 1 hour. (2.1) consistent with those observed in adults. (6.2) −Consider administering premedication for prophylaxis against infusion reactions and hypersensitivity reactions. (2.1) To report SUSPECTED ADVERSE REACTIONS, contact • Subcutaneous Administration in Adults with SLE GlaxoSmithKline at 1-877-423-6597 or FDA at 1-800-FDA-1088 or −200 mg once weekly. (2.2) www.fda.gov/medwatch. • Subcutaneous Administration in Adults with Lupus Nephritis See 17 for PATIENT COUNSELING INFORMATION and Medication −See Section 2.2. Guide. ------------------------- DOSAGE FORMS AND STRENGTHS------------------------ Revised: 03/2021 • Intravenous Infusion −For Injection: 120 mg or 400 mg lyophilized powder in single-dose vials for reconstitution and dilution prior to intravenous infusion. (3) FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 7 DRUG INTERACTIONS 2 DOSAGE AND ADMINISTRATION 8 USE IN SPECIFIC POPULATIONS 2.1 Intravenous Preparation and Dosing Instructions 8.1 Pregnancy 2.2 Subcutaneous Dosing Instructions 8.2 Lactation 3 DOSAGE FORMS AND STRENGTHS 8.3 Females and Males of Reproductive Potential 4 CONTRAINDICATIONS 8.4 Pediatric Use 5 WARNINGS AND PRECAUTIONS 8.5 Geriatric Use 5.1 Serious Infections 8.6 Renal Impairment 5.2 Hypersensitivity Reactions, including Anaphylaxis 8.7 Hepatic Impairment 5.3 Infusion Reactions 8.8 Racial Groups 5.4 Depression and Suicidality 10 OVERDOSAGE 5.5 Malignancy 11 DESCRIPTION 5.6 Immunization 12 CLINICAL PHARMACOLOGY 5.7 Concomitant Use with Other Biologic Therapies 12.1 Mechanism of Action 6 ADVERSE REACTIONS 12.2 Pharmacodynamics 6.1 Clinical Trials Experience with Intravenous Administration 12.3 Pharmacokinetics 6.2 Clinical Trials Experience with Subcutaneous 13 NONCLINICAL TOXICOLOGY Administration in Adults 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 6.3 Postmarketing Experience 14 CLINICAL STUDIES 6.4 Immunogenicity 14.1 Clinical Trials with Intravenous Administration in Adults with SLE 14.2 Clinical Trials with Intravenous Administration in Adults with Lupus Nephritis 1 14.3 Clinical Trials with Intravenous Administration in Pediatric 16.2 Subcutaneous Injection Patients with SLE 17 PATIENT COUNSELING INFORMATION 14.4 Clinical Trials with Subcutaneous Administration in Adults *Sections or subsections omitted from the full prescribing information are not with SLE listed. 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 Intravenous Infusion 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)]. 2 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 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. 4.