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Belimumab

Pronunciation

(be LIM yoo mab)

Dosage Forms

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

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: 5.29 L

Onset of Action

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

Half-Life Elimination

19.4 days

Use: Labeled Indications

Systemic lupus erythematosus: Treatment of adult patients 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 intravenous (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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

CrCl ≥15 mL/minute: No dosage adjustment necessary.

CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Reconstitution

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 sterile water for injection (SWFI). Reconstitute 400 mg vial with 4.8 mL of SWFI. 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 10-15 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 of 0.9% sodium chloride (dilute only in 0.9% sodium chloride) 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. Protect from light. Solution may be stored refrigerated or at room temperature.

Administration

Administer intravenously 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.

Compatibility

Incompatible with dextrose-containing solutions.

Storage

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, 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.

Drug Interactions

Abatacept: May enhance the adverse/toxic effect of Belimumab. Avoid combination

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

Belatacept: May enhance the adverse/toxic effect of Belimumab. 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

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Etanercept: May enhance the adverse/toxic effect of Belimumab. Avoid combination

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

Monoclonal Antibodies: May enhance the adverse/toxic effect of Belimumab. Avoid combination

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

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

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

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

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Vaccines (Inactivated): Belimumab may diminish the therapeutic effect of Vaccines (Inactivated). Management: Patients should receive inactivated vaccines prior to initiation of belimumab therapy whenever possible, due to the risk for an impaired response to the vaccine during belimumab therapy. 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 (13%)

Miscellaneous: Infusion related reaction (17%)

≥3% to 10%:

Central nervous system: Insomnia (6% to 7%), depression (5% to 6%), migraine (5%), anxiety (4%), headache (≥3%)

Dermatologic: Dermatological reaction (≥3%)

Gastrointestinal: Viral gastroenteritis (3%)

Genitourinary: Urinary tract infection (site not specified >5%), cystitis (4%)

Hematologic & oncologic: Leukopenia (4%)

Infection: Influenza (>5%)

Neuromuscular & skeletal: Limb pain (6%)

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

Miscellaneous: Fever (10%)

<3% (Limited to important or life-threatening): Anaphylaxis (including fatalities), antibody development, bradycardia, cellulitis, myalgia, pneumonia, progressive multifocal leukoencephalopathy (immune compromised), suicidal tendencies

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 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.

• 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: The most common symptoms reported included anxiety, depression, and/or insomnia. New onset or worsening of existing depression, and suicide, has been reported; most patients had a history of a psychiatric disorder and were already receiving treatment. Monitor for new or worsening depression, suicidal ideation or other mood changes.

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: May have a lower response rate; use with caution.

Monitoring Parameters

Monitor for hypersensitivity and/or infusion reactions; infections; worsening of depression, mood changes, or suicidal thoughts

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. IgG molecules are known to cross the placenta (belimumab is an engineered IgG molecule). Effective contraception should be used during and for at least 4 months following treatment in women of childbearing potential. Healthcare 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

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience pain in arms or legs, insomnia, diarrhea, abdominal pain, rhinitis, rhinorrhea, or pharyngitis. Have patient report immediately to prescriber signs of infection, signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), angina, bradycardia, muscle pain, severe headache, severe dizziness, passing out, shortness of breath, cold sweats, severe nausea, severe vomiting, or signs of progressive multifocal leukoencephalopathy (confusion, depression, trouble with memory, behavioral changes, change in strength on one side, trouble speaking, change in balance, or vision changes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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