BENLYSTA belimumab 200 mg/mL Solution, 1 syringe
🆔 Identity & classification
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🏭 Manufacturer & labeler
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🩺 Clinical
- Benlysta isn't a cure for lupus, but it helps control the disease. It targets an overactive part of your immune system that's driving inflammation and damage. It's used on top of y...
- What exactly is Benlysta treating — is it a cure for lupus?
- That depends on which form you're using. The intravenous (IV) version has to be given at a clinic or infusion center by a healthcare provider. The subcutaneous (under-the-skin) ver...
- Can I give myself the shot at home, or do I have to go to a clinic every time?
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🧪 Inactive Ingredients / Excipients
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UNII F7LTH1E20Y
Arginine hydrochloride is an amino acid salt used as a buffer and pH adjuster in medicines. It helps maintain the correct acidity level to keep the drug stable and effective.
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UNII 4QD397987E
An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
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UNII 1D5Q932XM6
An amino acid salt used in medicines as a buffer and pH regulator. It helps maintain the proper acidity level in liquid formulations to keep the drug stable and effective.
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UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
5 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $1,241.25 | $1,241.25 / 1 ml |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Benlysta 200 mg/mLthis 49401-0088-50 | GlaxoSmithKline | 1 syringe | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Jul 20, 2029 |
Is there a biosimilar for BENLYSTA 200 MG/ML AUTOINJECT?
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💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 49401-0088-02 | 1 SYRINGE in 1 CARTON (49401-088-02) / 1 mL in 1 SYRINGE (49401-088-01) | 2017-07-20 | Active |
| 49401-0088-35 | 4 SYRINGE in 1 CARTON (49401-088-35) / 1 mL in 1 SYRINGE (49401-088-01) | 2017-07-20 | Active |
| 49401-0088-47 | 4 SYRINGE in 1 CARTON (49401-088-47) / 1 mL in 1 SYRINGE (49401-088-42) | 2017-07-20 | Active |
| 49401-0088-50 You're viewing this | 1 SYRINGE in 1 CARTON (49401-088-50) / 1 mL in 1 SYRINGE (49401-088-42) | 2017-07-20 | Active |
| 49401-0088-61 | 1 SYRINGE in 1 CARTON (49401-088-61) / 1 mL in 1 SYRINGE | 2020-06-02 | Active |
This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓
Pack size FAQ
What quantity is in NDC 49401-0088-50?
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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.
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; ( 1 ) • Active lupus nephritis who are receiving standard therapy. ( 1 ) Limitations of Use: The efficacy of BENLYSTA has not been evaluated in patients with severe active central nervous system lupus. Use of BENLYSTA is not recommended in this situation.
( 1 )
⏱️ Dosage and Administration ▾
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: ( 2.3 ) 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. Indication Adults (Autoinjector or Prefilled Syringe) Pediatric Patients 5 Years of Age and Older (Weight ‑ Based Dosing) (Autoinjector Only) a Active SLE 200 mg once weekly • ≥40 kg: 200 mg once weekly • 15 kg to less than 40 kg: 200 mg once every 2 weeks Active Lupus Nephritis 400 mg b once weekly for 4 doses, followed by 200 mg once weekly • ≥40 kg: 400 mg b once weekly for 4 doses, followed by 200 mg once weekly • 15 kg to less than 40 kg: 200 mg once weekly for 4 doses, followed by 200 mg once every 2 weeks
2.1Important Administration Instructions BENLYSTA may be administered intravenously or subcutaneously [see Dosage and Administration ( 2.2 , 2.3 )]. 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). Precautions Prior to Intravenous Use BENLYSTA should be administered by healthcare providers prepared to manage anaphylaxis [see Warnings and Precautions ( 5.2 )].
Prior to intravenous dosing with BENLYSTA, consider administering premedication for prophylaxis against infusion reactions and hypersensitivity reactions [see Warnings and Precautions ( 5.2 ), Adverse Reactions ( 6.1 )] .
2.2Recommended Intravenous Dosage, and Preparation and Administration Instructions BENLYSTA for intravenous use must be reconstituted and diluted prior to administration. Do not administer as an intravenous push or bolus. Recommended Dosage and Administration The recommended intravenous BENLYSTA dosage in patients 5 years of age and older with active SLE or lupus nephritis 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. Do not concomitantly infuse BENLYSTA 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.
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 )] . Preparation of the Intravenous Solution 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. Direct the stream of sterile water towards the side of the vial to minimize foaming. Gently swirl the vial for 60 seconds.
Allow the vial to sit at room temperature during re…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Intravenous Infusion For injection: 120 mg or 400 mg of belimumab as a lyophilized powder in single‑dose vials for reconstitution and dilution prior to intravenous infusion. Subcutaneous Injection Injection: 200 mg/mL of belimumab as a clear to opalescent and colorless to pale yellow solution in a single-dose prefilled autoinjector or a single-dose prefilled glass syringe. • Intravenous Infusion (for injection): 120 mg or 400 mg of belimumab lyophilized powder in single‑dose vial for reconstitution and dilution prior to intravenous infusion.
( 3 ) • Subcutaneous Injection (injection): 200 mg/mL of belimumab in single‑dose prefilled autoinjector or single‑dose prefilled syringe. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS BENLYSTA is contraindicated in patients with a prior history of: • Anaphylaxis with belimumab [see Warnings and Precautions ( 5.2 )]. • Stevens-Johnson syndrome or toxic epidermal necrolysis with belimumab [see Warnings and Precautions ( 5.3 )]. Previous anaphylaxis, Stevens‑Johnson syndrome, or toxic epidermal necrolysis as a reaction to belimumab. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • 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.
( 5.1 ) • 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.
( 5.1 ) • Hypersensitivity Reactions, including Anaphylaxis: Serious and fatal reactions have been reported. ( 5.2 ) • Stevens‑Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN): Discontinue BENLYSTA immediately if signs or symptoms of SJS/TEN occur. ( 5.3 ) • Depression and Suicidality: Depression and suicidality were reported in trials with BENLYSTA.
Assess for depression and risk of suicide before treatment with BENLYSTA and monitor during treatment. Instruct patients to contact their healthcare provider if new or worsening depression, suicidal thoughts, or other mood changes occur. ( 5.4 ) • Immunization: Live vaccines should not be given concurrently with BENLYSTA.
( 5.6 )
5.1Serious Infections Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including BENLYSTA. Overall, the incidence of serious infections in controlled trials was similar in subjects receiving BENLYSTA compared with placebo, whereas fatal infections occurred more frequently in subjects receiving BENLYSTA [see Adverse Reactions ( 6.1 )] . Consider the risk and benefit before initiating treatment with BENLYSTA in patients with severe or chronic infections.
Consider interrupting therapy with BENLYSTA in patients who develop a new infection while receiving it and monitor these patients closely. Progressive Multifocal Leukoencephalopathy (PML) Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported in patients with SLE receiving immunosuppressants, including BENLYSTA. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function.
Consider the diagnosis of PML in any patient presenting with new-onset or deteriorating neurological signs and symptoms and consult with a neurologist or other appropriate specialist as clinically indicated. In patients with suspected PML, immunosuppressant therapy, including BENLYSTA, must be suspended until PML has been excluded. If PML is confirmed, immunosuppressant therapy, including BENLYSTA, must be discontinued.
5.2Hypersensitivity Reactions, including Anaphylaxis Acute hypersensitivity reactions, including anaphylaxis and death, and infusion-related reactions have been reported in association with BENLYSTA [see Adverse Reactions ( 6.1 )] . These events generally occurred within hours of the infusion; however, they may occur later. Non-acute hypersensitivity reactions including rash, nausea, fatigue, myalgia, headache, and facial edema have been reported and typically occurred up to a week following the most recent infusion.
Hypersensitivity, including serious reactions, has occurred in patients who have previously tolerated infusions of BENLYSTA. Limited data suggest that patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. Due to overlap in signs and symptoms, it was not possible to distinguish between hypersensitivity reactions and infusion-related reactions in all cases.
In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, some subjects (13%) received premedication, which may have mitigated or masked a hypersensitivity response or infusion-related reaction; however, there is ins…
🤒 Adverse Reactions ▾
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 )] • Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis [see Warnings and Precautions ( 5.3 )] • Depression and Suicidality [see Warnings and Precautions ( 5.4 )] • Malignancy [see Warnings and Precautions ( 5.5 )] Common adverse reactions (≥5%): nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, and injection site reactions (subcutaneous administration).
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-877-423-6597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Intravenous Administration in Adult Subjects with Active SLE The data described in Table 2 reflect exposure to BENLYSTA administered intravenously plus standard therapy compared with placebo plus standard therapy in 2,133 adult subjects with active SLE in 3 controlled trials (Trials 1, 2, and 3).
Subjects received BENLYSTA plus standard therapy at doses of 1 mg/kg (n = 673), 4 mg/kg (n = 111; Trial 1 only), or 10 mg/kg (n = 674), or placebo plus standard therapy (n = 675) intravenously over a 1‑hour period on Days 0, 14, 28, and then every 28 days. In 2 of the trials (Trial 1 and Trial 3), treatment was given for 48 weeks, while in the other trial (Trial 2) treatment was given for 72 weeks [see Clinical Studies ( 14.2 )] . Because there was no apparent dose‑related increase in the majority of adverse events observed with BENLYSTA, the safety data summarized below are presented for the 3 intravenous doses pooled, unless otherwise indicated; the adverse reaction table displays the results for the recommended intravenous dose of 10 mg/kg compared with placebo.
In Trials 1, 2, and 3, 93% of subjects treated with BENLYSTA plus standard therapy reported an adverse event compared with 92% treated with placebo plus standard therapy. The most common serious adverse events were serious infections (6% and 5.2% in the groups receiving BENLYSTA and placebo plus standard therapy, respectively), some of which were fatal. The most commonly reported adverse events, occurring in ≥5% of subjects in Trials 1, 2, and 3 were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis.
The proportion of subjects who discontinued treatment due to any adverse reaction during Trials 1, 2, and 3 was 6.2% for subjects receiving BENLYSTA plus standard therapy and 7.1% for subjects receiving placebo plus standard therapy. The most common adverse reactions resulting in discontinuation of treatment (≥1% of subjects receiving BENLYSTA or placebo) were infusion reactions (1.6% BENLYSTA and 0.9% placebo), lupus nephritis (0.7% BENLYSTA and 1.2% placebo), and infections (0.7% BENLYSTA and 1% placebo). Table 2 lists adverse reactions, regardless of causality, occurring in at least 3% of subjects with active SLE who received BENLYSTA 10 mg/kg plus standard therapy and at an incidence at least 1% greater than that observed with placebo plus standard therapy in 3 controlled trials (Trials 1, 2, and 3).
Table 2. Incidence of Adverse Reactions Occurring in at Least 3% of Adult Subjects with Active SLE Treated with BENLYSTA 10 mg/kg plus Standard Therapy and at Least 1% More Frequently than in Subjects Receiving Placebo plus Standard Therapy (Trials 1, 2, and 3) Adverse Reactions BENLYSTA 10 mg/kg + Standard Therapy (n = 674) % Placebo + Standard Therapy (n = 675) % Nausea 15 12 Diarrhea…
🔄 Drug 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.
The effect of belimumab on the pharmacokinetics of other drugs has not been evaluated [see Clinical Pharmacology ( 12.3 )] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that evaluates pregnancy outcomes in women with lupus exposed to BENLYSTA during pregnancy. Healthcare professionals are encouraged to refer patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/benlysta-belimumab/ . Risk Summary Available data on use of BENLYSTA in pregnant women, from observational studies, published case reports, and postmarketing surveillance, are insufficient to determine whether there is a drug-associated risk for major birth defects or miscarriage.
There are risks to the mother and fetus associated with SLE (see Clinical Considerations ) . Monoclonal antibodies, such as belimumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero-exposed infant (see Clinical Considerations ) . In an animal combined embryo-fetal and pre- and post-natal development study with monkeys that received belimumab by intravenous administration, there was no evidence of fetal harm with exposures approximately 9 times (based on intravenous administration) and 20 times (based on subcutaneous administration) the exposure at the maximum recommended human dose (MRHD).
Belimumab-related findings in monkey fetuses and/or infants included reductions of B-cell counts, reductions in the density of lymphoid tissue B-lymphocytes in the spleen and lymph nodes, and altered IgG and IgM titers. The no-adverse-effect-level (NOAEL) was not identified for these findings; however, they were reversible within 3 to 12 months after the drug was discontinued (see Data ) . Based on animal data and the mechanism of action of belimumab, the immune system in infants of treated mothers may be adversely affected.
It is unknown, based on available data, whether immune effects, if identified, are reversible [see Clinical Pharmacology ( 12.1 )] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. Maternal lupus nephritis increases the risk of hypertension and preeclampsia/eclampsia.
Passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block. Fetal/Neonatal Adverse Reactions: Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to BENLYSTA in utero.
Monitor an infant of a treated mother for B-cell reduction and other immune dysfunction [see Warnings and Precautions ( 5.6 )] . Data Animal Data: In a combined embryo-fetal and pre- and post-natal development study, pregnant cynomolgus monkeys received belimumab at intravenous doses of 0, 5, or 150 mg/kg every 2 weeks from confirmation of pregnancy at Gestation Days (GD) 20 to 22, throughout the period of organogenesis (up to approximately GD 50), and continuing to either the day of scheduled cesarean section (GD 150 [late third trimester]) or the day of parturition.
There was no evidence of maternal toxicity, effects on embryofetal and infant survival, or structural abnormalities at exposure approximately 9 times the MRHD of 10 mg/kg intravenously or 20 times t…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that evaluates pregnancy outcomes in women with lupus exposed to BENLYSTA during pregnancy. Healthcare professionals are encouraged to refer patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/benlysta-belimumab/ . Risk Summary Available data on use of BENLYSTA in pregnant women, from observational studies, published case reports, and postmarketing surveillance, are insufficient to determine whether there is a drug-associated risk for major birth defects or miscarriage.
There are risks to the mother and fetus associated with SLE (see Clinical Considerations ) . Monoclonal antibodies, such as belimumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero-exposed infant (see Clinical Considerations ) . In an animal combined embryo-fetal and pre- and post-natal development study with monkeys that received belimumab by intravenous administration, there was no evidence of fetal harm with exposures approximately 9 times (based on intravenous administration) and 20 times (based on subcutaneous administration) the exposure at the maximum recommended human dose (MRHD).
Belimumab-related findings in monkey fetuses and/or infants included reductions of B-cell counts, reductions in the density of lymphoid tissue B-lymphocytes in the spleen and lymph nodes, and altered IgG and IgM titers. The no-adverse-effect-level (NOAEL) was not identified for these findings; however, they were reversible within 3 to 12 months after the drug was discontinued (see Data ) . Based on animal data and the mechanism of action of belimumab, the immune system in infants of treated mothers may be adversely affected.
It is unknown, based on available data, whether immune effects, if identified, are reversible [see Clinical Pharmacology ( 12.1 )] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. Maternal lupus nephritis increases the risk of hypertension and preeclampsia/eclampsia.
Passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block. Fetal/Neonatal Adverse Reactions: Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to BENLYSTA in utero.
Monitor an infant of a treated mother for B-cell reduction and other immune dysfunction [see Warnings and Precautions ( 5.6 )] . Data Animal Data: In a combined embryo-fetal and pre- and post-natal development study, pregnant cynomolgus monkeys received belimumab at intravenous doses of 0, 5, or 150 mg/kg every 2 weeks from confirmation of pregnancy at Gestation Days (GD) 20 to 22, throughout the period of organogenesis (up to approximately GD 50), and continuing to either the day of scheduled cesarean section (GD 150 [late third trimester]) or the day of parturition.
There was no evidence of maternal toxicity, effects on embryofetal and infant survival, or structural abnormalities at exposure approximately 9 times the MRHD of 10 mg/kg intravenously or 20 times the MRHD of 200 mg subcutaneous…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of BENLYSTA have been established for the treatment of active SLE and active lupus nephritis in pediatric patients 5 years of age and older who are receiving standard therapy. The safety and effectiveness of BENLYSTA have not been established in pediatric patients less than 5 years of age. Intravenous Use Use of BENLYSTA intravenously in pediatric patients 5 years of age and older with active SLE is supported by evidence from pharmacokinetic (PK), safety, and efficacy results from a pediatric trial (Trial 6), as well as PK exposure and extrapolation of the established efficacy of BENLYSTA plus standard therapy from the Phase 3 intravenous studies in adults with active SLE (Trials 2 and 3).
In Trial 6, the proportion of pediatric subjects achieving an SRI‑4 response was higher in subjects receiving BENLYSTA plus standard therapy compared with placebo plus standard therapy. Pediatric subjects receiving BENLYSTA plus standard therapy also had a lower risk of experiencing a severe flare compared with placebo plus standard therapy [see Clinical Studies ( 14.4 )] . Pharmacokinetics were evaluated in a total of 53 pediatric subjects (Trial 6) and were consistent with the adult population with active SLE [see Clinical Pharmacology ( 12.3 )] .
Use of BENLYSTA intravenously in pediatric patients 5 years of age and older with active lupus nephritis is based on the extrapolation of efficacy from the intravenous trial (Trial 5) in adults (n = 224) with active lupus nephritis, and supported by pharmacokinetic data from intravenous studies in adults (n = 224) with active lupus nephritis and from pediatric subjects (n = 53) with active SLE (Trial 6). Estimated belimumab exposures for pediatric patients were comparable to adults with active lupus nephritis [see Clinical Pharmacology ( 12.3 )] .
Subcutaneous Use Use of BENLYSTA, administered subcutaneously in pediatric patients 5 years of age and older who weigh at least 15 kg with active SLE, is supported by evidence from an open‑label pharmacokinetic trial (subcutaneous administration of BENLYSTA in pediatric subjects with active SLE) and Trial 6 (a pharmacokinetic, efficacy, and safety trial of intravenous dosing in pediatric subjects with active SLE). The pharmacokinetics of belimumab, following subcutaneous administration in pediatric patients, are estimated to be comparable to adults who receive BENLYSTA subcutaneously and pediatric patients who receive BENLYSTA intravenously [see Clinical Pharmacology ( 12.3 )] .
Use of BENLYSTA, administered subcutaneously in pediatric patients 5 years of age and older who weigh at least 15 kg with active lupus nephritis, is based on the extrapolation of efficacy from the intravenous trial in adults (n = 224) with active lupus nephritis (Trial 5), and is supported by pharmacokinetic data derived from the same adult trial (Trial 5), a pharmacokinetic, efficacy, and safety intravenous trial in pediatric subjects with active SLE (n = 53) (Trial 6), and an open‑label subcutaneous trial in pediatric subjects with active SLE (n = 25).
Belimumab exposures for pediatric patients with active lupus nephritis following subcutaneous administration are estimated to be comparable to adults with active lupus nephritis who receive BENLYSTA intravenously [see Clinical Pharmacology ( 12.3 )] .
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of BENLYSTA did not include sufficient numbers of subjects, 65 years of age or older, to determine whether they respond differently from younger subjects. Use with caution in geriatric patients.
🆘 Overdosage ▾
10 OVERDOSAGE There is limited experience with overdosage of belimumab. Two doses of up to 20 mg/kg have been given intravenously to humans with no increase in incidence or severity of adverse reactions compared with doses of 1, 4, or 10 mg/kg.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.2Pharmacodynamics 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.
Treatment with BENLYSTA in adult subjects led to reductions in IgG and anti‑double‑stranded DNA antibodies (anti‑dsDNA) which were observed as early as Week 8 and sustained through Week 52. In subjects with low complement levels at baseline, treatment led to increases in complement C3 and C4 as early as Week 12 and were sustained through Week 52. The pharmacodynamic response observed in Black subjects (Trial 4) was consistent with the previous studies.
In subjects with active lupus nephritis (Trial 5), following treatment with BENLYSTA, there was a decrease in serum IgG as early as Week 4, and subsequently there was an increase in serum IgG levels which was associated with decreased proteinuria. Reductions in autoantibodies, increases in complement, and reductions in circulating total B cells and B‑cell subsets observed were consistent with the SLE studies. In Trial 6 (pediatric dosing), the pharmacodynamic response was consistent with the adult data.
The clinical relevance of above mentioned pharmacodynamic biomarkers has not been established.
12.3Pharmacokinetics Intravenous Infusion in Adults Systemic Lupus Erythematosus: The pharmacokinetic parameters displayed in Table 3 are based on population parameter estimates from 563 adult subjects with active SLE who received BENLYSTA 10 mg/kg . Table 3. Population Pharmacokinetic Parameters in Adult Subjects with Active SLE after Intravenous Infusion of BENLYSTA 10 mg/kg a a Intravenous infusions were administered at 2‑week intervals for the first 3 doses and at 4‑week intervals thereafter.
Pharmacokinetic Parameter Population Estimates (n = 563) Peak concentration at steady state (C max,ss , mcg/mL) 313 Area under the curve (AUC 0-∞ , day•mcg/mL) 3,083 Distribution half-life (t ½ , days)
1.8 Terminal half-life (t ½ , days)
19.4Systemic clearance (CL, mL/day) 215 Volume of distribution at steady state (Vss, L) 5 Lupus Nephritis: A population pharmacokinetic analysis was conducted in 224 adult subjects with active lupus nephritis who received belimumab 10 mg/kg intravenously (Days 0, 14, 28, and then every 28 days up to 104 weeks) plus standard therapy in Trial 5 [see Clinical Studies ( 14.3 )] . In these subjects, due to additional clearance associated with proteinuria, belimumab exposure was initially lower than observed in SLE studies and lower belimumab exposure was observed in subjects with higher proteinuria.
When the proteinuria was decreased to approximately ≤1 g/g after treatment, belimumab clearance and exposure were similar to that observed in subjects with active SLE who received belimumab 10 mg/kg intravenously. The available data do not support a dose adjustment in patients with high proteinuria. Subcutaneous Injection in Adults Systemic Lupus Erythematosus: The pharmacokinetic parameters displayed in Table 4 are based on population parameter estimates from 661 adult subjects with active SLE after subcutaneous administration of belimumab 200 mg once weekly.
The time to reach maximum serum concentration (C max ) was 2.6 days (T max ) after administration at steady state. The bioavailability of belimumab was approximately 74%. With weekly subcutaneous administration there were minor fluctuations around…
🧬 Mechanism of Action ▾
12.1Mechanism 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1Intravenous Infusion BENLYSTA (belimumab) for injection is a sterile, preservative-free, lyophilized powder for reconstitution and dilution prior to intravenous infusion provided in single‑dose glass vials with a rubber stopper (not made with natural rubber latex) and a flip‑off seal. Each 5‑mL vial contains 120 mg of belimumab. Each 20‑mL vial contains 400 mg of belimumab.
BENLYSTA vials are supplied as follows: 120 mg belimumab in a 5‑mL single-dose vial (NDC 49401-101-01) 400 mg belimumab in a 20‑mL single-dose vial (NDC 49401-102-01) Refrigerate vials at 36°F to 46°F (2°C to 8°C). Store vials in the original carton until use to protect from light. Do not freeze.
Avoid exposure to heat.
16.2Subcutaneous Injection BENLYSTA (belimumab) injection is a clear to opalescent, and colorless to pale yellow solution for subcutaneous use. Each single-dose prefilled autoinjector or single-dose prefilled syringe is designed to deliver 200 mg of belimumab in 1 mL of solution and is supplied as follows: 200 mg/mL single-dose prefilled autoinjector with 27-gauge, half-inch needle attached (NDC 49401-088-01) in a carton of 4 (NDC 49401-088-35). 200 mg/mL single-dose prefilled glass syringe with 27-gauge, half-inch needle attached (NDC 49401-088-42) in a carton of 4 (NDC 49401-088-47).
Prior to Dispensing Refrigerate prefilled autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C). Keep the product in the original carton to protect from light until the time of use. Do not freeze.
Do not shake. Avoid exposure to heat. Following Dispensing Refrigerate prefilled autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C).
Keep the product in the original carton to protect from light until the time of use. Do not freeze. Do not shake.
Avoid exposure to heat. 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.
📋 Description ▾
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.
Intravenous Infusion BENLYSTA (belimumab) for injection is a sterile, white to off-white, preservative‑free, lyophilized powder in a single-dose vial for reconstitution and dilution prior to intravenous infusion. BENLYSTA for injection is supplied as 120 mg per vial and 400 mg per vial and requires reconstitution with Sterile Water for Injection, USP (1.5 mL and 4.8 mL, respectively) to obtain a concentration of 80 mg/mL [see Dosage and Administration ( 2.2 )] . After reconstitution, each vial allows for withdrawal of 1.5 mL (120 mg) or 5 mL (400 mg).
Each mL delivers 80 mg belimumab, citric acid (0.16 mg), polysorbate 80 (0.4 mg), sodium citrate (2.7 mg), and sucrose (80 mg), with a pH of 6.5. The vial stoppers are not made with natural rubber latex. Subcutaneous Injection BENLYSTA (belimumab) injection is a sterile, preservative-free, clear to opalescent, and colorless to pale yellow solution for subcutaneous use.
It is supplied in a 1-mL single-dose prefilled autoinjector with a fixed 27-gauge, half-inch needle or in a 1-mL single-dose prefilled syringe with a fixed 27-gauge, half-inch needle with a needle guard. Each 1 mL delivers 200 mg belimumab, L-arginine hydrochloride (5.3 mg), L-histidine (0.65 mg), L-histidine monohydrochloride (1.2 mg), polysorbate 80 (0.1 mg), and sodium chloride (6.7 mg), with a pH of 6.0. The autoinjectors and prefilled syringes are not made with natural rubber latex.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). It is important that the patient’s overall health be assessed at each visit and any questions resulting from the patient’s reading of the Medication Guide and Instructions for Use be discussed. For patients receiving BENLYSTA, give patients the Medication Guide for BENLYSTA.
Serious Infections Inform patients that BENLYSTA may decrease their ability to fight infections, and that serious infections, including some fatal ones, occurred in patients receiving BENLYSTA in clinical trials. Instruct patients to tell their healthcare provider if they develop signs or symptoms of an infection [see Warnings and Precautions ( 5.1 )] . Progressive Multifocal Leukoencephalopathy Advise patients to contact their healthcare professional if they experience new or worsening neurological symptoms such as memory loss, confusion, dizziness or loss of balance, difficulty talking or walking, or vision problems [see Warnings and Precautions ( 5.1 )] .
Hypersensitivity Reactions/Anaphylaxis Educate patients on the signs and symptoms of hypersensitivity reactions and infusion-related reactions, including wheezing, difficulty breathing, angioedema, rash, hypotension, bradycardia, and headache. Instruct patients to immediately tell their healthcare provider if they experience symptoms of an allergic reaction during or after the administration of BENLYSTA. Inform patients about possible delayed reactions that may include a combination of symptoms such as rash, nausea, fatigue, muscle aches, headache, and/or facial swelling that may occur after administration of BENLYSTA and advise them to contact their healthcare provider [see Warnings and Precautions ( 5.2 )] .
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Advise patients about signs and symptoms of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Instruct patients to stop taking any further doses of BENLYSTA and immediately call their healthcare provider if they experience signs and symptoms suggestive of SJS/TEN [see Warnings and Precautions ( 5.3 )] . Depression and Suicidality Instruct patients (and caregivers if applicable) to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts, or other mood changes [see Warnings and Precautions ( 5.4 )] .
Immunizations Inform patients that they should not receive live vaccines while taking BENLYSTA. Response to vaccinations could be impaired by BENLYSTA [see Warnings and Precautions ( 5.6 )] . Pregnancy Registry Inform patients that there is a pregnancy registry to evaluate fetal outcomes of pregnant women with lupus exposed to BENLYSTA [see Use in Specific Populations ( 8.1 )] .
Pregnancy Inform female patients of reproductive potential that BENLYSTA may impact the immune system in infants of treated mothers and to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations ( 8.1 )] .
💬 Medication Guide ▾
MEDICATION GUIDE BENLYSTA (ben-LIST-ah) (belimumab) for injection, for intravenous use BENLYSTA (ben-LIST-ah) (belimumab) injection, for subcutaneous use What is the most important information I should know about BENLYSTA? Immunosuppressive agents, including BENLYSTA can cause serious side effects. Some of these side effects may cause death.
The following are serious adverse reactions that have occurred in patients receiving BENLYSTA: 1. Infections. Infections could be serious, leading to hospitalization or death.
Tell your healthcare provider right away if you have any of the following symptoms of an infection: • fever • chills • pain or burning with urination • urinating often • coughing up mucus • warm, red, or painful skin or sores on your body 2. Allergic (hypersensitivity) reactions. Serious allergic reactions can happen on the day of, or in the days after, receiving BENLYSTA and may cause death.
Your healthcare provider will watch you closely while you are receiving BENLYSTA given in a vein (intravenous infusion) and after your infusion for signs of a reaction. Allergic reactions can sometimes be delayed. Tell your healthcare provider right away if you have any of the following symptoms of an allergic reaction following use of BENLYSTA: • itching • swelling of the face, lips, mouth, tongue, or throat • trouble breathing • anxiousness • low blood pressure • dizziness or fainting • headache • nausea • skin rash 3.
Severe skin reactions. Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, can occur with BENLYSTA. Stop using BENLYSTA right away and tell your healthcare provider if you develop any of the signs and/or symptoms of a severe skin reaction listed below.
These may sometimes begin with fever and flu-like symptoms. Your healthcare provider will permanently stop your treatment with BENLYSTA if a severe skin reaction is confirmed: • painful rash, with reddish non-elevated, target-like or circular patches on the trunk often with central blisters • widespread skin peeling or blistering • ulcers often appearing in the eyes, nose, mouth, throat, and genitals 4. Mental health problems and suicide.
Symptoms of mental health problems can occur. Tell your healthcare provider right away if you have any of the following symptoms: • thoughts of suicide or dying • attempt to commit suicide • trouble sleeping (insomnia) • new or worse anxiety • new or worse depression • acting on dangerous impulses • other unusual changes in your behavior or mood • thoughts of hurting yourself or others What is BENLYSTA? • BENLYSTA is a prescription medicine used to treat adults and children 5 years of age and older with: o active systemic lupus erythematosus (SLE or lupus) who are receiving other lupus medicines, and o active lupus nephritis (lupus‑related kidney inflammation), who are receiving other lupus medicines. • BENLYSTA contains belimumab which is in a group of medicines called monoclonal antibodies.
Lupus is a disease of the immune system (the body system that fights infection). When given together with other medicines for lupus, BENLYSTA decreases lupus disease activity more than other lupus medicines alone. • It is not known if BENLYSTA is safe and effective in people with severe active central nervous system lupus. • It is not known if BENLYSTA is safe and effective for use in children less than 5 years of age. • It is not known if BENLYSTA, given under the skin (subcutaneously), is safe and effective for use in children who weigh less than 33 pounds (15 kilograms).
Do not use BENLYSTA if you: • are allergic to belimumab or any of the ingredients in BENLYSTA. See the end of this Medication Guide for a complete list of ingredients in BENLYSTA. • had Stevens-Johnson syndrome or toxic epidermal necrolysis with BENLYSTA. Before you receive BENLYSTA, tell your healthcare provider about all of your medical conditions, including if you: • think you have an infection or have infections that keep coming b…