Belimumab

BENLYSTA is indicated for the treatment of patients 5 years of age and older with: • Active systemic lupus erythematosus (SLE) who are receiving standard therapy, and • 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 (CNS) lupus. Use of BENLYSTA is not recommended in this situation. BENLYSTA is a B-lymphocyte stimulator (BLyS)-specific inhibitor indicated for the treatment of patients 5 years of age and older with: • Active systemic lupus erythematosus (SLE) who are receiving standard therapy,. • 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 is a BLyS-specific inhibitor that blocks the binding of soluble BLyS, a B-cell survival factor, to its receptors on B cells. BENLYSTA does not bind B cells directly, but by binding BLyS, BENLYSTA inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

• See Full Prescribing Information for complete preparation and administration information. • Intravenous dosage for active SLE or lupus nephritis: o 10 mg/kg at 2‑week intervals for the first 3 doses and at 4‑week intervals thereafter. o Reconstitute, dilute, and administer as an intravenous infusion over a period of 1 hour. o Consider prophylactic premedication for infusion reactions and hypersensitivity reactions. • Subcutaneous dosage for active SLE or lupus nephritis: a Prefilled syringe has not been studied in children less than 18 years of age. b The 400-mg dose requires administration of two 200‑mg injections.

BENLYSTA is contraindicated in patients with a prior history of: • Anaphylaxis with belimumab. • Stevens-Johnson syndrome or toxic epidermal necrolysis with belimumab. Previous anaphylaxis, Stevens‑Johnson syndrome, or toxic epidermal necrolysis as a reaction to belimumab.

• Serious Infections: Serious and sometimes fatal infections have occurred in patients receiving immunosuppressive agents, including BENLYSTA. Use with caution in patients with severe or chronic infections. Consider interrupting therapy with BENLYSTA if patients develop a new infection during treatment with BENLYSTA. • Progressive Multifocal Leukoencephalopathy (PML): Evaluate patients with new-onset or deteriorating neurological signs and symptoms for PML. If PML is suspected, immunosuppressant therapy, including BENLYSTA, must be suspended until PML has been excluded. If PML is confirmed, immunosuppressant therapy, including BENLYSTA, must be discontinued. • Hypersensitivity Reactions, including Anaphylaxis: Serious and fatal reactions have been reported.

The following serious adverse reactions are described below and in the Warnings and Precautions section: • Serious Infections • Hypersensitivity Reactions, including Anaphylaxis • Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis • Depression and Suicidality • Malignancy Common adverse reactions (≥5%): nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, and injection site reactions (subcutaneous administration).

Formal drug interaction studies have not been performed with BENLYSTA. In clinical trials, BENLYSTA was administered concomitantly with other drugs, including corticosteroids, antimalarials, immunomodulatory and immunosuppressive agents (including azathioprine, cyclophosphamide, methotrexate, and mycophenolate), angiotensin pathway antihypertensives, HMG‑CoA reductase inhibitors (statins), and/or non-steroidal anti-inflammatory drugs (NSAIDs) without evidence of a clinically meaningful effect of these concomitant medications on belimumab pharmacokinetics. The effect of belimumab on the pharmacokinetics of other drugs has not been evaluated.

Do not freeze. Prior to Dispensing Refrigerate prefilled autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C). Do not freeze. Following Dispensing Refrigerate prefilled autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C). Do not freeze. BENLYSTA may be stored outside of the refrigerator up to 86°F (30°C) for up to 12 hours if protected from sunlight. Do not use and do not place back in refrigerator if left out for more than 12 hours. Store vials in the original carton until use to protect from light. Keep the product in the original carton to protect from light until the time of use. Do not shake. Do not shake.