Belimumab (Monograph)

Brand name: Benlysta
Drug class: Immunosuppressive Agents

Medically reviewed by Drugs.com on Mar 10, 2024. Written by ASHP.

Introduction

Immunosuppressive agent; recombinant fully human IgG₁ lambda monoclonal antibody that inhibits soluble B-lymphocyte stimulator (BLyS).

Uses for Belimumab

Systemic Lupus Erythematosus

Management of active systemic lupus erythematosus (SLE) in adults and pediatric patients ≥5 years of age. Appears to modestly reduce disease activity in patients with severe autoantibody-positive SLE.

Not recommended in patients with severe active CNS lupus.

Use in conjunction with other standard SLE therapies (e.g., corticosteroids, antimalarials, NSAIAs, and/or immunosuppressive agents [e.g., azathioprine, cyclophosphamide, methotrexate, mycophenolate]).

Standard treatment of SLE includes hydroxychloroquine and glucocorticoids with or without immunomodulating/immunosuppressive agents (e.g., methotrexate, azathioprine, mycophenolate). In patients with an inadequate response to the standard therapies, biologic agents may be considered as add-on therapy. The European Alliance of Associations for Rheumatology (EULAR) guidelines state that add-on belimumab should be considered in patients with persistently active or flaring disease.

Lupus Nephritis

Management of active lupus nephritis in adults and pediatric patients ≥5 years of age.

Use in conjunction with other standard therapies for lupus nephritis.

The Kidney Disease: Improving Global Outcomes (KDIGO) guideline provides recommendations for treatment of patients with SLE, including those with lupus nephritis. The guideline states that belimumab can be added to standard therapy in the treatment of active lupus nephritis.

Belimumab Dosage and Administration

General

Pretreatment Screening

• Consider the potential risks and benefits before initiating belimumab in patients with severe or chronic infections.

• Assess the risk of depression and suicide considering the patient’s medical history and current psychiatric status before initiating belimumab.

Patient Monitoring

• If a patient develops a new infection during treatment, consider interruption of belimumab therapy and monitor the patient closely.

• Consider the diagnosis of progressive multifocal leukoencephalopathy (PML) in any patient presenting with new-onset or deteriorating neurological signs and symptoms; consult with a neurologist or other appropriate specialist as clinically indicated.

• Monitor patients for hypersensitivity reactions and infusion-related reactions during and for an appropriate period of time after IV administration of belimumab.

• Monitor patients for new or worsening depression, suicidal thoughts or behavior, or other mood changes.

Premedication and Prophylaxis

• Consider premedication prior to IV infusion of the drug to minimize the risk of infusion and hypersensitivity reactions.

• Belimumab by IV infusion should be administered by healthcare providers prepared to manage anaphylaxis.

Administration

Administer by IV infusion or sub-Q injection.

Available as single-dose vials of lyophilized powder, which is intended for IV use following reconstitution and dilution; do not use for sub-Q administration. Also commercially available as autoinjectors and prefilled syringes, which are intended for sub-Q use only (not for IV use).

IV Administration

May administer by IV infusion in patients ≥5 years of age. Do not administer by rapid IV injection (e.g., IV push or bolus).

Do not infuse concomitantly in the same IV line with other agents.

Belimumab lyophilized powder is intended for IV use only and must be reconstituted and diluted prior to IV administration. Complete infusion within 8 hours of reconstitution.

Reconstitution

Allow vial to stand at room temperature for 10–15 minutes before reconstitution.

Add 1.5 or 4.8 mL of sterile water for injection to a vial containing 120 or 400 mg of belimumab powder, respectively, to provide a solution containing 80 mg/mL. Use a 21- to 25-gauge needle when piercing the vial stopper for reconstitution and dilution. Direct sterile water diluent toward side of vial to minimize foaming. Gently swirl vial for 60 seconds every 5 minutes until the powder is dissolved; do not shake.

Dissolution usually occurs within 10–15 minutes but may require up to 30 minutes.

Protect the reconstituted solution from direct sunlight.

Dilution

Dilute reconstituted solution with 0.9% sodium chloride injection, 0.45% sodium chloride injection, or lactated Ringer’s injection to a final volume of 250 mL. For patients whose body weight is ≤40 kg, a volume of 100 mL may be used such that the resulting belimumab concentration in the infusion bag does not exceed 4 mg/mL.

Prior to adding the reconstituted solution to the infusion bag or bottle, withdraw and discard a volume of 0.9% sodium chloride injection, 0.45% sodium chloride injection, or lactated Ringer’s injection equal to the volume of reconstituted solution to be added. Add the total required volume of reconstituted belimumab to the diluent. Gently invert the infusion bag or bottle to mix thoroughly; do not shake.

Rate of Administration

Infuse over 1 hour.

If an infusion reaction occurs, slow or interrupt the infusion. If a serious hypersensitivity reaction occurs, stop the infusion immediately.

Sub-Q Administration

May administer by sub-Q injection in patients ≥18 years of age.

Belimumab prefilled autoinjectors and prefilled syringes are intended for sub-Q use only.

Belimumab for sub-Q use may be self-administered if the clinician determines that the patient and/or their caregiver is competent to prepare and safely administer the drug after appropriate training and with medical follow-up as necessary. Initial self-administered dose should be made under supervision of a qualified healthcare provider; educate patients about signs and symptoms of hypersensitivity reactions.

Allow single-dose prefilled autoinjector or syringe to sit at room temperature for at least 30 minutes prior to administration; do not warm any other way. Prior to administration, inspect solution through window of prefilled autoinjector or syringe visually for particulate matter or discoloration. Solution should be clear to opalescent and colorless to pale yellow; discard if it is discolored or cloudy, or if foreign particulate matter is present.

Administer sub-Q injections of belimumab into abdomen or thigh; rotate injection sites. Do not administer into areas where skin is tender, bruised, red, or hard. When a 400-mg dose is administered at the same site, administer the 2 individual 200-mg injections ≥5 cm apart.

Dosage

Pediatric Patients

Systemic Lupus Erythematosus

IV

Pediatric patients ≥5 years of age: 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter.

Lupus Nephritis

IV

Pediatric patients ≥5 years of age: 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter.

Adults

Systemic Lupus Erythematosus

IV

10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter.

Sub-Q

200 mg once weekly (preferably on the same day each week).

If transitioning from IV therapy, administer first sub-Q dose 1–4 weeks after last IV dose.

Lupus Nephritis

IV

10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter.

Sub-Q

400 mg (two 200-mg injections) once weekly for 4 doses, then 200 mg once weekly thereafter.

May transition from IV therapy to sub-Q administration any time following completion of ≥2 IV doses. Administer first sub-Q dose of 200 mg 1–2 weeks after the last IV dose.

Special Populations

Hepatic Impairment

No dosage adjustment required.

Renal Impairment

No dosage adjustment required.

Geriatric Patients

No specific dosage recommendations; use with caution.

Cautions for Belimumab

Contraindications

• Known history of anaphylaxis to belimumab.

Warnings/Precautions

Infectious Complications

Serious, sometimes fatal infections (e.g., bronchitis, pneumonia, urinary tract infection, cellulitis) reported.

Consider potential risks and benefits before initiating belimumab in patients with severe or chronic infections.

If a new infection develops, consider interrupting belimumab therapy and monitor the patient closely.

PML, an opportunistic infection of the brain caused by the polyomavirus JC (also called the JC virus) that is sometimes fatal, reported in patients treated with immunosuppressive agents, including belimumab. Associated with high levels of overall immunosuppression and impairment of immune function.

Consider diagnosis of PML in any patient presenting with new-onset or deteriorating neurological signs and symptoms; consult with a neurologist or other appropriate specialist as clinically indicated.

In patients with suspected PML, must suspend immunosuppressant therapy, including belimumab, until PML has been excluded. If PML is confirmed, must discontinue immunosuppressant therapy, including belimumab.

Sensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, hypotension, angioedema, urticaria or other rash, pruritus, dyspnea) reported in 13% of adult patients with SLE receiving IV belimumab. Not possible in all cases to distinguish between hypersensitivity and infusion reactions.

Insufficient experience to establish whether premedication regimens reduce the frequency or severity of hypersensitivity reactions.

Administer IV by healthcare providers prepared to manage anaphylaxis. If a serious hypersensitivity reaction occurs, immediately discontinue infusion and provide appropriate supportive care. Monitor during and for an appropriate period of time after administration. Consider administering premedication as prophylaxis prior to IV administration of belimumab.

Infusion Reactions

Infusion reactions (e.g., headache, nausea, skin reactions) reported in 17% of adult patients with SLE receiving IV belimumab. Serious reactions have included bradycardia, myalgia, headache, rash, urticaria, and hypotension.

Insufficient experience to establish whether premedication regimens reduce the frequency or severity of infusion reactions.

Administer IV by healthcare providers prepared to manage infusion reactions. If an infusion reaction occurs, interrupt or slow the infusion.

Psychiatric Effects

Psychiatric events (e.g., depression, insomnia, anxiety, suicidality) reported. Most patients reporting serious depression or suicidal behavior had a history of depression or other serious psychiatric disorders and most were receiving psychoactive drugs. Unknown if belimumab increases risk for these events.

Assess risk of depression and suicide considering patient’s medical history and current psychiatric status before initiating belimumab and continue to monitor patients during treatment. Consider potential risks and benefits of continued treatment with belimumab in patients who develop new or worsening depression, suicidal thoughts or behavior, or other mood changes.

Malignancy

Immunosuppressive therapy may increase risk of malignancies. Effect of belimumab on the development of malignancies is unknown. Malignancies were reported during clinical trials.

Consider individual benefit-to-risk ratio in patients with known risk factors for development or reoccurrence of malignancy prior to initiating belimumab. In patients who develop malignancies, consider potential risks and benefits of continued treatment with the drug.

Immunization

Avoid live vaccines.

Concomitant Therapy

Efficacy and safety in combination with other biologic therapies not established, including B-cell-targeted therapies; use with caution in combination with other biologics. D

Available data do not support concomitant use of belimumab and rituximab in patients with SLE; increased incidence of serious infections and systemic injection reactions reported in patients receiving such concomitant therapy.

Immunogenicity

Antibodies to belimumab, including neutralizing antibodies, detected. Mild infusion-related reactions reported in several patients with antibody formation; however, clinical importance of antibelimumab antibodies is unknown.

Specific Populations

Pregnancy

Data in pregnant women insufficient to determine whether there is a risk of major birth defects or miscarriage associated with belimumab.

Based on animal data and drug's mechanism of action, the immune system in infants of women receiving belimumab during pregnancy may be adversely affected; reversibility of these potential effects unknown.

Monoclonal antibodies, such as belimumab, are increasingly transported across the placenta as pregnancy progresses, with largest amount transferred during third trimester. Consider potential risks and benefits prior to administering live or live-attenuated vaccines to infants exposed to belimumab in utero. Monitor infants born to women receiving belimumab during pregnancy for B-cell reduction and other immune dysfunction.

Benlysta pregnancy registry at 877-681-6296.

Lactation

Distributed into milk in cynomolgus monkeys; not known whether distributed into human milk, affects milk production, or affects the breast-fed infant. Consider developmental and health benefits of breast-feeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breast-fed child from belimumab or the underlying maternal condition.

Females of Reproductive Potential

Following an assessment of benefit versus risk, if prevention of pregnancy is warranted, females of reproductive potential should use effective contraceptive methods during belimumab therapy and for ≥4 months after discontinuance of the drug.

Pediatric Use

Safety and efficacy of IV belimumab not established in pediatric patients <5 years of age.

Safety and efficacy of sub-Q belimumab not established in pediatric patients <18 years of age.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; use with caution.

Hepatic Impairment

No formal studies of effects of hepatic impairment on pharmacokinetics.

Renal Impairment

Studied in a limited number of patients with mild, moderate, or severe renal impairment.

Black/African-American Patients

In 2 studies in patients with SLE, response rates were lower for Black patients receiving IV belimumab than for Black patients receiving placebo.

In another study, response rates were numerically higher in Black patients receiving IV belimumab than for those receiving placebo; however, treatment difference not statistically significant.

Safety profile of belimumab in Black patients consistent with known safety profile in overall population of patients studied.

Common Adverse Effects

Adverse effects (reported in ≥5% of patients): Nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, injection site reactions (with sub-Q administration).

Drug Interactions

No formal drug interaction studies to date.

Vaccines

No data available on effects of immunization in patients receiving belimumab. Belimumab may interfere with immune response to vaccines.

Avoid live vaccines during and within 30 days prior to initiation of belimumab therapy; safety not established. No data available on secondary transmission of infection by live vaccines in belimumab-treated patients.

Specific Drugs

Belimumab Pharmacokinetics

Absorption

Bioavailability

Sub-Q: 74%.

Plasma Concentrations

Peak plasma concentrations achieved in 2.6 days following sub-Q administration at steady state.

Steady-state concentrations achieved from week 2 of dosing with sub-Q loading dose of 400 mg weekly in patients with lupus nephritis. Average concentrations at steady state with weekly maintenance dosing of belimumab 200 mg sub-Q predicted to be similar to those observed following belimumab 10 mg/kg IV every 4 weeks.

Special Populations

Body weight and body mass index do not have clinically important effects on belimumab pharmacokinetics following sub-Q administration of the drug.

Elimination

Half-life

IV: 19.4 days.

Sub-Q: 18.3 days.

Special Populations

Hepatic impairment: Pharmacokinetics not formally studied. Baseline transaminase (AST, ALT) did not explain variability in drug clearance.

Renal impairment: Pharmacokinetics not formally studied. In population pharmacokinetic analyses in patients with lupus nephritis receiving IV belimumab, drug clearance was increased with proteinuria, but effects are unlikely to be clinically important.

Stability

Storage

Parenteral

Powder for Injection

2–8°C. Protect from light; do not freeze.

If reconstituted solution is not used immediately, store at 2–8°C and protect from direct sunlight. Store diluted solution at 2–8°C or room temperature. Total time from reconstitution to completion of infusion should not exceed 8 hours.

Sub-Q Injection

Store belimumab prefilled autoinjectors or prefilled syringes at 2–8°C in the original carton for protection from light until time of use. Do not shake, freeze, or expose to heat.

May store individual single-dose prefilled syringes and single-use prefilled autoinjectors at room temperature (20–25°C) for a up to 12 hours, with protection from sunlight.

Discard once drug has been stored at room temperature for >12 hours; do not use or place back in refrigerator.

Discard and do not use any belimumab autoinjector or prefilled syringe that has been dropped on a hard surface.

Actions

• Inhibits biologic effects of soluble BLyS. BLyS inhibits B-cell apoptosis and stimulates differentiation of B cells into immunoglobulin-producing plasma cells.

• Inhibits binding of soluble BLyS to its receptors on B cells, thereby inhibiting B-cell (including autoreactive B-cell) survival and reducing differentiation of B cells into immunoglobulin-producing plasma cells.

• Treatment reduces circulating CD19⁺, CD20⁺, naive, and activated B cells, and the SLE B-cell subset, as well as IgG and antibodies to double-stranded DNA (anti-dsDNA). Memory cells increase initially and slowly decline toward baseline. Complement (C3 and C4) levels are increased in patients with low complement levels at baseline. Clinical relevance of these effects not definitively established.

Advice to Patients

• Importance of advising the patient to read the medication guide and instructions for use.

• If a sub-Q dose is missed, advise patient to administer as soon as remembered. Resume dosing on usual day of administration, or start a new weekly schedule from the day the missed dose was administered.

• Risk of increased susceptibility to infection, potentially life-threatening. Importance of promptly informing clinicians if any signs or symptoms of infection (e.g., fever, chills, pain or burning on urination, frequent urination, bloody diarrhea, cough) develop.

• Risk of progressive multifocal leukoencephalopathy. Advise patient to contact clinician in case of new or worsening neurological symptoms (e.g., memory loss, confusion, dizziness or loss of balance, difficulty talking or walking, or vision problems).

• Risk of hypersensitivity reactions, including anaphylaxis, and infusion-related reactions. Importance of seeking immediate medical care if signs or symptoms of hypersensitivity or infusion-related reactions (e.g., wheezing, difficulty breathing, perioral or lingual edema, rash, hypotension, bradycardia, headache) occur. Inform patients about possible delayed reactions that may include a combination of symptoms (e.g., rash, nausea, fatigue, muscle aches, headache, and/or facial swelling) and to contact their clinician if these occur.

• Importance of advising patients and/or caregivers to promptly report new or worsening depression, suicidal thoughts, or other mood changes.

• Importance of not receiving live vaccines during belimumab therapy.

• Importance of promptly reporting symptoms of cardiac disease (e.g., chest discomfort or pain, shortness of breath, cold sweats, nausea, dizziness).

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise female patients of reproductive potential that belimumab may impact the immune system in infants of treated mothers. Inform patients that there is a pregnancy registry to monitor fetal outcomes of pregnant women exposed to belimumab.

• Inform females of reproductive potential to use effective contraception during therapy and for at least 4 months after discontinuing the drug.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal or dietary supplements, as well as any concomitant illnesses or history of chronic infections.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• What is the difference between Benlysta and Saphnelo?

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