Overview
11 DESCRIPTION Belimumab is a human IgG1λ monoclonal antibody specific for soluble human B lymphocyte stimulator protein (BLyS, also referred to as BAFF and TNFSF13B). Belimumab has a molecular weight of approximately 147 kDa. Belimumab is produced by recombinant DNA technology in a murine cell (NS0) expression system.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.2 Pharmacodynamics Treatment with BENLYSTA in adult subjects significantly reduced circulating CD19+, CD20+, naïve, and activated B cells, and the SLE B‑cell subset at Week 52. Reductions in naïve and the SLE B‑cell subset were observed as early as Week 8 and sustained to Week 52. Memory cells increased initially and slowly declined toward baseline levels by Week 52.
Indications
- 1 INDICATIONS AND USAGE 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.
Common Doses
- 10 mg
- 200 mg
- 400 mg
- 80 mg
Dosage
2 DOSAGE AND ADMINISTRATION • See Full Prescribing Information for complete preparation and administration information. ( 2.1 , 2.2 , 2.3 ) • 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. ( 2.2 ) o Consider prophylactic premedication for infusion reactions and hypersensitivity reactions. ( 2.1 , 2.2 ) • Subcutaneous dosage for active SLE or lupus nephritis: ( 2.
Contraindications
- 4 CONTRAINDICATIONS BENLYSTA is contraindicated in patients who have had anaphylaxis with belimumab. Previous anaphylaxis to belimumab. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are described below and in the Warnings and Precautions section: • Serious Infections [see Warnings and Precautions ( 5.1 )] • Hypersensitivity Reactions, including Anaphylaxis [see Warnings and Precautions ( 5.2 )] • Depression and Suicidality [see Warnings and Precautions ( 5.3 )] • Malignancy [see Warnings and Precautions ( 5.4 )] Common adverse reactions (≥5%): nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, and injection site reactions (subcutaneous...
Interactions
- 7 DRUG INTERACTIONS 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.