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Belimumab

Medically reviewed by Drugs.com. Last updated on Oct 8, 2020.

Pronunciation

(be LIM yoo mab)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Auto-injector, Subcutaneous [preservative free]:

Benlysta: 200 mg/mL (1 mL) [contains polysorbate 80]

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Benlysta: 200 mg/mL (1 mL) [contains polysorbate 80]

Solution Reconstituted, Intravenous [preservative free]:

Benlysta: 120 mg (1 ea); 400 mg (1 ea) [contains polysorbate 80]

Brand Names: U.S.

  • Benlysta

Pharmacologic Category

  • Monoclonal Antibody

Pharmacology

Belimumab is an IgG1-lambda monoclonal antibody that prevents the survival of B lymphocytes by blocking the binding of soluble human B lymphocyte stimulator protein (BLyS) to receptors on B lymphocytes. This reduces the activity of B-cell mediated immunity and the autoimmune response.

Distribution

Vd: 5 L

Onset of Action

B cells: 8 weeks; Clinical improvement (SLE Responder Index and flare reduction): 16 weeks (Navarra 2011)

Time to Peak

SubQ: 2.6 days

Half-Life Elimination

Terminal: IV: 19.4 days; SubQ: 18.3 days

Use: Labeled Indications

Systemic lupus erythematosus: Treatment of adults and children ≥5 years of age with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy.

Limitations of use: Use is not recommended in patients with severe active lupus nephritis, severe active CNS lupus, or in combination with other biologics, including B-cell targeted therapies or IV cyclophosphamide.

Contraindications

Hypersensitivity (anaphylaxis) to belimumab or any component of the formulation

Dosing: Adult

Systemic lupus erythematosus (SLE):

IV: Initial: 10 mg/kg every 2 weeks for 3 doses; Maintenance: 10 mg/kg every 4 weeks

SubQ: 200 mg once weekly

Switching from IV therapy: Administer the first SubQ dose 1 to 4 weeks after the last IV dose.

Missed dose: If a dose is missed, administer the dose as soon as possible and then resume the original schedule on the usual day of administration or start a new weekly schedule based on the date that the missed dose was administered.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Consider premedication for prevention of hypersensitivity and infusion reactions.

Systemic lupus erythematosus (SLE):

IV: Children ≥5 years and Adolescents: Initial: 10 mg/kg/dose every 2 weeks for 3 doses; followed by maintenance therapy of 10 mg/kg/dose every 4 weeks.

SubQ: Adolescents ≥18 years: 200 mg once weekly; preferably on the same day each week.

Conversion from IV therapy: Administer the first SubQ dose 1 to 4 weeks after the last IV dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

IV: To reconstitute, remove vial from the refrigerator and allow to stand 10 to 15 minutes to reach room temperature. Reconstitute 120 mg vial with 1.5 mL of SWFI. Reconstitute 400 mg vial with 4.8 mL of SWFI. A 21- to 25-gauge needle is recommended to use for piercing the vial stopper for reconstitution and dilution. To minimize foaming, direct SWFI toward the side of the vial. Gently swirl for 60 seconds every 5 minutes until powder has dissolved (usual reconstitution time is 10 to 15 minutes, but may take up to 30 minutes); do not shake. If utilizing a mechanical reconstitution device, do not exceed 500 rpm or 30 minutes. Further dilute reconstituted solution in 250 mL (or 100 mL for patients ≤40 kg) of NS, 0.45% NS, or lactated Ringer's by first removing and discarding the volume equivalent to the volume of the reconstituted solution to be added to prepare the appropriate dose; add the appropriate volume of the reconstituted solution to the infusion container and gently invert to mix solution.

SubQ: Remove the autoinjector or prefilled syringe from the refrigerator and allow to sit at room temperature for 30 minutes prior to administration; do not warm product in any other way. Visually inspect the window of the autoinjector or prefilled syringe for particulate matter or discoloration. Do not use if product exhibits discoloration or if dropped on a hard surface.

Administration

IV: Administer IV over 1 hour through a dedicated IV line. Do NOT administer as an IV push or bolus. Discontinue infusion for severe hypersensitivity reaction (eg, anaphylaxis, angioedema). The infusion may be slowed or temporarily interrupted for minor reactions. Consider premedicating with an antihistamine and antipyretic for prophylaxis against hypersensitivity or infusion reactions.

SubQ: Allow prefilled syringe and autoinjector to warm to room temperature for 30 minutes prior to administration; do not warm product in any other way. Administer SubQ using a different injection site on the same day each week; do not administer into tender, bruised, red, or hard skin. Initial use is recommended under supervision of physician; self-injection may occur after proper training.

Storage

IV: Prior to reconstitution, store unused vials between 2°C and 8°C (36°F and 46°F); do not freeze. Protect from light. Avoid exposure to heat. Prior to further dilution in NS, 0.45% NS, or lactated Ringer's, the reconstituted solution must be stored under refrigeration. The diluted solution may be stored refrigerated or at room temperature. Infusion must be completed within 8 hours of reconstitution.

SubQ: Refrigerate prefilled autoinjectors and prefilled syringes at 2°C to 8°C (36°F to 46°F). Keep in original carton to protect from light. Do not freeze. Do not shake. Avoid exposure to heat. May be stored outside of the refrigerator up to 30°C (86°F) for up to 12 hours in the original container. Do not use and do not place back in refrigerator if left out for more than 12 hours.

Drug Interactions

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Biologic Anti-Psoriasis Agents: Belimumab may enhance the immunosuppressive effect of Biologic Anti-Psoriasis Agents. Avoid combination

Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): Belimumab may enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Cyclophosphamide: Belimumab may enhance the adverse/toxic effect of Cyclophosphamide. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Inebilizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Management: Concomitant use of upadacitinib with potent immunosuppressants is not recommended. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Belimumab may enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Adverse Reactions

>10%:

Gastrointestinal: Diarrhea (12%), nausea (15%)

Hypersensitivity: Hypersensitivity reaction (13%)

Infection: Infection (IV: 71%, SubQ: 55%)

Nervous system: Psychiatric disturbance (16%; serious: 1%)

Miscellaneous: Infusion related reaction (17%)

1% to 10%:

Dermatologic: Dermatological reaction (≥3%)

Gastrointestinal: Viral gastroenteritis (3%)

Genitourinary: Cystitis (4%), urinary tract infection (>5%)

Hematologic & oncologic: Leukopenia (4%)

Immunologic: Antibody development (≤5%)

Infection: Influenza (>5%), serious infection (6%)

Local: Injection site reaction (6%)

Nervous system: Anxiety (4%), depression (5% to 6%), headache (≥3%), insomnia (6% to 7%), migraine (5%), suicidal behavior (≤1%), suicidal ideation (≤1%)

Neuromuscular & skeletal: Limb pain (6%)

Respiratory: Bronchitis (9%), nasopharyngitis (9%), pharyngitis (5%), sinusitis (>5%), upper respiratory tract infection (>5%)

Miscellaneous: Fever (10%)

Frequency not defined:

Dermatologic: Cellulitis

Respiratory: Pneumonia

<1%:

Cardiovascular: Bradycardia

Neuromuscular & skeletal: Myalgia

Postmarketing:

Hypersensitivity: Anaphylaxis, angioedema

Nervous system: Progressive multifocal leukoencephalopathy

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity/infusion reactions: Acute hypersensitivity reactions including anaphylaxis (with fatalities) have been reported, including patients who had previously tolerated infusions of belimumab; onset may occur within hours of the infusion or may be delayed. Non-acute hypersensitivity reactions, including facial edema, fatigue, headache, myalgia, nausea, and rash have been reported and may occur up to a week following infusion. Risk for hypersensitivity reactions may be increased with history of multiple drug allergies or significant hypersensitivity. Infusion-related reactions (which may be difficult to distinguish from hypersensitivity) may also occur; symptoms may include angioedema, bradycardia, dyspnea, headache, hypotension, myalgia, pruritus, rash, and urticaria. Monitor for hypersensitivity and infusion-related reactions for an appropriate time following administration and immediately discontinue for severe reactions (and administer appropriate medical treatment) or slow or temporarily interrupt infusion for other infusion reactions. It is unknown if premedication prevents or reduces the severity of hypersensitivity reactions.

• Infections: Serious and potentially fatal infections may occur during treatment. Use with caution in patients with severe or chronic infections; treatment should not be undertaken if receiving therapy for chronic infection. Consider interrupting belimumab in patients who develop new infections and initiate appropriate anti-infective treatment; monitor closely.

• Malignancy: Immunosuppressant therapy may increase the risk of malignancy.

• Mortality: Deaths due to infection, cardiovascular disease, and suicide were higher in belimumab patients compared to placebo during clinical trials in adults.

• Progressive multifocal leukoencephalopathy: Cases of progressive multifocal leukoencephalopathy (PML) associated with JC virus (some fatal) have been reported in patients with systemic lupus erythematosus (SLE) receiving immunosuppressants, including belimumab. Risk factors for PML include immunosuppressant therapies and impaired immune function. Consider diagnosis of PML in any patient presenting with new-onset or deteriorating neurologic signs/symptoms; consult a neurologist (or other appropriate specialist). If PML is confirmed, consider discontinuing immunosuppressant treatment, including belimumab.

• Psychiatric events: Psychiatric disorders (including depression and suicidal ideation and behavior) have been reported. Prior to and during treatment, the risk of depression and suicide should be assessed based on medical history and current psychiatric status. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior, new-onset or worsening depression, anxiety, or other mood changes; risk and benefit of continued treatment should be assessed for patients who develop such symptoms.

Concurrent drug therapy issues:

• Immunizations: Live vaccines should not be given within 30 days before or concurrently with belimumab; there is no data available concerning secondary transmission of infection from live vaccines.

Special populations:

• Black/African-American patients: Response rates may be altered in this population; use with caution.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Monitoring Parameters

Monitor during and for an appropriate time after administration for hypersensitivity and/or infusion reactions; infections; worsening of depression, mood changes, or suicidal thoughts

Reproductive Considerations

Females of reproductive potential should use effective contraception during therapy and for at least 4 months after the last belimumab dose.

Based on limited information, use of belimumab may be continued through conception in women with rheumatic and musculoskeletal diseases who are planning a pregnancy and not able to use alternative therapies; use should be discontinued once pregnancy is confirmed. Conception should be planned during a period of quiescent/low disease activity (ACR [Sammaritano 2020]).

Recommendations for use of belimumab to treat rheumatic and musculoskeletal diseases in males who are planning to father a child are not available due to limited data (ACR [Sammaritano 2020]).

Pregnancy Considerations

Belimumab is a humanized monoclonal antibody (IgG1). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Information related to use of belimumab in pregnancy is limited (Bitter 2018; Danve 2014; Emmi 2016; Kumthekar 2017). If exposure occurs during pregnancy, the manufacturer recommends monitoring the newborn for B-cell reduction and other immune dysfunction.

Until additional information is available, belimumab is not currently recommended for the treatment of rheumatic and musculoskeletal diseases during pregnancy. Belimumab should be discontinued once pregnancy is confirmed (ACR [Sammaritano 2020]).

Health care providers are encouraged to enroll women exposed to belimumab during pregnancy in a pregnancy registry (877-681-6296); patients may also enroll themselves.

Patient Education

What is this drug used for?

• It is used to treat lupus.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Painful extremities

• Trouble sleeping

• Diarrhea

• Stuffy nose

• Injection site irritation

• Sore throat

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infusion reaction

• Infection

• Depression like thoughts of suicide, anxiety, emotional instability, or confusion.

• Chest pain

• Slow heartbeat

• Muscle pain

• Severe headache

• Dizziness

• Passing out

• Shortness of breath

• Cold sweats

• Severe nausea

• Vomiting

• Progressive multifocal leukoencephalopathy like confusion, depression, trouble with memory, behavioral changes, change in strength on one side is greater than the other, trouble speaking, change in balance, or vision changes.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.