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]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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
Dosage and Administration
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.
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.
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. 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
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. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. 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. 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
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. 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: Nausea (15%), diarrhea (12%)
Hypersensitivity: Hypersensitivity reaction (13%)
Infection: Infection (71%)
Miscellaneous: Infusion related reaction (17%)
1% to 10%:
Central nervous system: Insomnia (6% to 7%), depression (5% to 6%), migraine (5%), anxiety (4%), headache (≥3%), suicidal behavior (≤1%), suicidal ideation (≤1%)
Dermatologic: Dermatological reaction (≥3%)
Gastrointestinal: Viral gastroenteritis (3%)
Genitourinary: Urinary tract infection (>5%), cystitis (4%)
Hematologic & oncologic: Leukopenia (4%)
Immunologic: Antibody development (≤5%)
Infection: Serious infection (6%), influenza (>5%)
Local: Injection site reaction (6%)
Neuromuscular & skeletal: Limb pain (6%)
Respiratory: Bronchitis (9%), nasopharyngitis (9%), sinusitis (>5%), upper respiratory tract infection (>5%), pharyngitis (5%)
Miscellaneous: Fever (10%)
Frequency not defined:
Dermatologic: Cellulitis
Respiratory: Pneumonia
<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, bradycardia, dyspnea, eyelid edema, facial edema, fatigue, hypotension, myalgia, progressive multifocal leukoencephalopathy, pruritus, skin rash, urticaria
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:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- 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
Pregnancy
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).
If exposure occurs during pregnancy, monitor the newborn for B-cell reduction and other immune dysfunction and consider risks and benefits prior to administering live vaccines
Effective contraception should be used during and for at least 4 months following treatment in women of childbearing potential.
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.
Frequently reported side effects of this drug
- Painful extremities
- Trouble sleeping
- Diarrhea
- Stuffy nose
- Injection site irritation
- Sore throat
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- 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 a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
