Belimumab

Name: Belimumab

What is belimumab, and how does it work (mechanism of action)?

Belimumab is a synthetic (man-made) injectable antibody that reduces the activity of immune cells called B-cells in patients with systemic lupus erythematosus (SLE). SLE is an inflammatory autoimmune disease, which means that the body's immune system attacks its own tissues and causes inflammation. Parts of the body affected by SLE include the heart, skin, joints, kidneys, lungs, and brain. Common symptoms include rash, fever, chest pain, hair loss, joint pain, fatigue, and sensitivity to light.

One type of immune cell that is involved in the immune attack in SLE is the B-cell. One of the functions of B-cells is to produce antibodies, proteins that the body usually produces to fight infection. The B-cells in SLE produce antibodies that may be involved in the autoimmune attack in SLE. Belimumab blocks the action of B-cell (lymphocyte) stimulator (BLyS) protein, which B-cells require for survival. By blocking BLys, belimumab reduces the number of B-cells available to produce antibodies that contribute to SLE. In clinical studies, belimumab-treated patients experienced less activity of their SLE than those who received other SLE therapies. Belimumab was approved by the FDA in March 2011.

Belimumab Food Interactions

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of belimumab there are no specific foods that you must exclude from your diet when receiving belimumab.

 

Belimumab Usage

This medication comes in an injectable form that is given through a needle in a vein (IV) by a healthcare provider or injected under the skin (subcutaneous) at home. 

Injected into a vein by a healthcare provider:

  • You will be given belimumab by a healthcare provider through a needle placed in a vein (IV infusion). It takes about 1 hour to give you the full dose of belimumab. 
  • Your healthcare provider will tell you how often you should receive belimumab. 
  • Your healthcare provider may give you medicines before you receive belimumab to help reduce your chance of having a reaction. A healthcare provider will watch you closely while you are receiving belimumab and after your infusion for signs of a reaction.  

Injected under the skin (subcutaneous) at home:

  • This medication will be injected under the skin of your stomach (abdomen) or thigh. 
  • Use Benlysta 1 time a week on the same day each week.
  • Use this medication exactly as your healthcare provider tells you to. Read the Instructions for Use that comes with this medication for instructions about the right way to give your injections at home.
  • This medication may be prescribed as a single-dose autoinjector or as a single-dose prefilled syringe.
  • Before you use belimumab, your healthcare provider will show you or your caregiver how to give the injections and review the signs and symptoms of possible allergic reactions.
  • If you miss your dose of belimumab on your planned day, inject a dose as soon as you remember. Then, inject your next dose at your regularly scheduled time or continue weekly dosing based on the new day injected. In case you are not sure when to inject belimumab, call your healthcare provider. Do not use 2 doses on the same day to make up for a missed dose.

Belimumab Dosage

Take this medication exactly as prescribed by your doctor.

If injected into the vein:

  • The dose your doctor recommends may be based on your weight.
  • The recommended dose of belimumab is 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter.

If injected under the skin:

  • 200 mg once weekly.

 

Dosing & Uses

Dosing Form & Strengths

IV solution

  • 120mg/vial
  • 400mg/vial

SC solution

  • 200mg/mL single-dose, prefilled syringe or autoinjector

Systemic Lupus Erythematosus

Indicated for active, autoantibody-positive lupus (systemic lupus erythematosus) who are receiving standard therapy, including corticosteroids, antimalarials, immunosuppressives, and nonsteroidal anti-inflammatory drugs

Also see Administration

IV

  • Must be administered by healthcare professional in clinic/hospital setting
  • Initial: 10 mg/kg IV q2Weeks x3 doses, THEN  
  • Maintenance: 10 mg/kg IV q4Weeks

SC

  • After training from their health care provider, patients may self-administer SC dose
  • 200 mg SC once weekly
  • If transitioning from IV to SC, administer the first SC dose 1-4 weeks after the last IV dose

Dosage Modifications

Renal or hepatic impairment: No dosage adjustment recommended for any degree of impairment

Dosing Considerations

Limitations of use

  • Efficacy has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus, and has not been studied in combination with other biologics or IV cyclophosphamide; not recommended in these situations

Safety and efficacy not established

Pharmacology

Mechanism of Action

Inhibits the biological activity of B-lymphocyte stimulator (BLyS); BLyS is a naturally occurring protein required for survival and development of B-lymphocyte cells into mature plasma B cells that produce antibodies

In autoimmune diseases, elevated BLyS levels are thought to contribute to production of autoantibodies

Belimumab specifically recognizes and binds to BLyS, inhibits BLyS’s stimulation of B-cell development, and finally, restores the potential for autoantibody-producing B cells to undergo the normal process of apoptosis (programmed cell death)

Absorption

Peak Plasma Concentration: 313 mcg/mL

AUC: 3,083 days•mcg/mL

Distribution

Vd: 5.29 L

Elimination

Half-Life: 1.75 days (distribution); 19.4 days (terminal)

Clearance: 215 mL/day

Administration

IV Compatibilities

0.9% NaCl (normal saline)

IV Incompatibilities

Dextrose solutions

IV Preparation

Lyophilized powder in a single-use vial for intravenous infusion only and should be reconstituted and diluted using aseptic technique

Remove vial from refrigerator; let stand for 10-15 minutes to reach room temperature

Reconstitution

  • Reconstitute powder with sterile water for injection to final concentration of 80 mg/mL
  • 120 mg vial: Reconstitute with 1.5 mL sterile water for injection
  • 400 mg vial: Reconstitute with 4.8 mL sterile water for injection
  • Direct stream of sterile water toward side of vial to minimize foaming
  • DO NOT SHAKE; gently swirl vial for 60 seconds every 5 minutes until powder is dissolved
  • Reconstitution is typically complete within 10-15 minutes, but may take up to 30 minutes
  • Note: If mechanical reconstitution device is used, it should not exceed 500 rpm and the vial swirled for no longer than 30 minutes
  • Once reconstituted, the solution should be opalescent and colorless to pale yellow, and without particles; small air bubbles are expected and acceptable

Dilution

  • Dilute reconstituted solution in 0.9% NaCl 250 mL
  • From 250 mL bag/bottle of 0.9% NaCl, withdraw and discard volume equal to volume of the reconstituted solution required for the patient’s dose
  • Add required volume of reconstituted solution to infusion bag/bottle
  • Gently invert bag/bottle to mix the solution
  • Vial is for single use; discard any unused portion
  • Total time from reconstitution to completion of infusion should not exceed 8 hours

IV Administration

Administer diluted solution IV over 1 hour

Administer by health care providers prepared to manage anaphylaxis

Do not infuse concomitantly in same IV line with other drugs

Consider administering premedication (ie, antihistamines, corticosteroids) for prophylaxis against infusion reactions and hypersensitivity

SC Preparation

Instruct patient to remove the autoinjector or prefilled syringe from the refrigerator and allow it to sit at room temperature for 30 minutes prior to the SC injection; do not warm drug in any other way

Visually inspect the window of the autoinjector or the prefilled syringe for particulate matter or discoloration; solution should be clear to opalescent and colorless to pale yellow

Do not use if the product exhibits discoloration or particulate matter

Instruct the patient not to use autoinjector or prefilled syringe if dropped on a hard surface

SC Administration

Administer SC once weekly, preferably on the same day each week

Administer SC in abdomen or thigh

When injecting in the same body region, advise the patient to use a different injection site each week; never give injections into areas where the skin is tender, bruised, red, or hard

Missed dose

  • Administer missed dose as soon as the patient remembers
  • Thereafter, the patient can resume dosing on their usual day of administration or start a new weekly schedule from the day that the missed dose was administered
  • Not recommended to administer 2 doses on the same day

Storage

Unopened IV vials

  • Store refrigerated 2-8°C (36-46°F); do not freeze
  • Store vials in original carton and protect from light until use
  • Avoid exposure to heat

Reconstituted IV vials

  • If not used immediately, may be stored refrigerated 2-8°C (36-46°F)
  • For single use only; discard any unused portion

Diluted IV solution

  • May be stored refrigerated 2-8°C (36-46°F) or at room temperature
  • Total time from reconstitution to completion of infusion should not exceed 8 hours

SC prefilled syringes or autoinjector

  • Refrigerated
    • Refrigerate prefilled syringe or autoinjectors at 2-8°C (36-46°F)
    • Keep product in the original carton to protect from light until the time of use
    • Do not freeze, shake, or expose to heat
  • Nonrefrigerated
    • May be stored outside of the refrigerator up to 86°F (30°C) for up to 12 hr in the original container
    • Do not use and do not place back in refrigerator if left out for >12 hr

What should I avoid while receiving belimumab?

Avoid being near people who have colds, the flu, or other contagious illnesses.

Do not receive a "live" vaccine while using belimumab. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Belimumab dosing information

Usual Adult Dose for Systemic Lupus Erythematosus:

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

Comments:
-Infuse over a 1-hour period.
-Consider premedication including an antihistamine, with or without an antipyretic, before the infusion.

Use: Treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy.

Cautions for Belimumab

Contraindications

  • Known history of anaphylaxis to belimumab.1

Warnings/Precautions

Mortality

More deaths were reported with belimumab than with placebo in clinical studies in SLE.1 Etiologies included infection, cardiovascular disease, and suicide; however, no single cause of death predominated.1

Infectious Complications

Serious, sometimes fatal infections (e.g., bronchitis, pneumonia, urinary tract infection, cellulitis) reported.1

Use caution when considering belimumab in patients with chronic infections.1 Do not begin therapy with belimumab in patients receiving any therapy for chronic infection.1

If a new infection develops, consider interrupting belimumab therapy and monitor the patient closely.1

Malignancy

Immunosuppressive therapy may increase risk of malignancies.1 Effect of belimumab on the development of malignancies is unknown.1 Malignancies were reported during clinical trials. 1

Sensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, hypotension, angioedema, urticaria or other rash, pruritus, dyspnea) reported in 13% of patients.1 Not possible in all cases to distinguish between hypersensitivity and infusion reactions.1

Insufficient experience to establish whether premedication regimens reduce the frequency or severity of hypersensitivity reactions.1

Administer by healthcare providers prepared to manage anaphylaxis.1 If a serious hypersensitivity reaction occurs, immediately discontinue infusion and provide appropriate supportive care.1 Monitor during and for an appropriate period of time after administration.1

Infusion Reactions

Infusion reactions (e.g., headache, nausea, skin reactions) reported in 17% of patients.1 Serious reactions have included bradycardia, myalgia, headache, rash, urticaria, and hypotension.1

Insufficient experience to establish whether premedication regimens reduce the frequency or severity of infusion reactions.1

Administer by healthcare providers prepared to manage infusion reactions.1 If an infusion reaction occurs, interrupt or slow the infusion.1

Psychiatric Effects

Psychiatric events (e.g., depression, insomnia, anxiety) reported.1 Most patients reporting serious depression or suicidal behavior had a history of depression or other serious psychiatric disorders and most were receiving psychoactive drugs.1 Unknown if belimumab increases risk for these events.1

Immunization

Avoid live vaccines.1 (See Vaccines under Interactions.)

Concomitant Therapy

Not studied in combination with other biologic therapies, including B-cell-targeted therapies, or IV cyclophosphamide; use not recommended in combination with these therapies.1

Immunogenicity

Antibodies to belimumab, including neutralizing antibodies, detected.1 Mild infusion-related reactions reported in several patients with antibody formation; however, clinical importance of antibelimumab antibodies is unknown.1

Specific Populations

Pregnancy

Category C.1 Women of childbearing potential should use effective contraceptive method during treatment and for ≥4 months after discontinuance of the drug.1

Benlysta pregnancy registry (for clinicians and patients) at 877-681-6296.1

Lactation

Distributed into milk in cynomolgus monkeys; not known whether distributed into human milk or absorbed systemically following ingestion.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in children.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; use with caution.1

Hepatic Impairment

No formal studies of effects of hepatic impairment on pharmacokinetics.1 Not studied in patients with severe hepatic impairment.1

Renal Impairment

Studied in a limited number of patients with moderate to severe renal impairment.1

Blacks

Limited experience in black patients with SLE.1 11 13 Response in phase 2 study did not appear to vary by race; however, exploratory analysis of phase 3 data indicated response rates were lower for blacks receiving belimumab than for blacks receiving placebo.1 No definitive conclusions can be drawn; use caution when considering belimumab for treatment of SLE in black patients.1

Common Adverse Effects

Nausea,1 3 diarrhea,1 3 pyrexia,1 nasopharyngitis,1 bronchitis,1 insomnia,1 pain in extremity,1 depression,1 migraine,1 3 pharyngitis.1

Advice to Patients

  • Importance of the patient reading the medication guide before initiating therapy and before each subsequent infusion.1 2

  • Importance of informing patients that there were more deaths among belimumab-treated patients than among placebo recipients during clinical trials in patients with SLE.1

  • Risk of increased susceptibility to infection.1 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.1 2

  • Risk of hypersensitivity reactions, including anaphylaxis.1 2 Importance of seeking immediate medical care if signs or symptoms of hypersensitivity reactions (e.g., wheezing, difficulty breathing, perioral or lingual edema, rash) occur.1 2

  • Importance of promptly reporting new or worsening depression, suicidal thoughts, or other mood changes.1 2

  • Importance of not receiving live vaccines during belimumab therapy.1 2

  • Importance of promptly reporting symptoms of cardiac disease (e.g., chest discomfort or pain, shortness of breath, cold sweats, nausea, dizziness).2

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 Advise women of childbearing potential to use effective contraceptive method during treatment and for ≥4 months following discontinuance of the drug.1

  • 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.1 2

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Dosing Hepatic Impairment

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

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

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 confusion), 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, memory impairment, behavioral changes, change in strength on one side is greater than the other, difficulty 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 health care 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.

Liver Dose Adjustments

Data not available

Belimumab Breastfeeding Warnings

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Yes

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