belimumab (Rx)

>10%

Infusion related reactions, common (17%) (ie, nausea, headache, skin reactions)

Nausea (15%)

Hypersensitivity reactions (13%)

Diarrhea (12%)

Pyrexia (10%)

1-10%

Nasopharyngitis (9%)

Bronchitis (9%)

Insomnia (7%)

Local injection site reaction, SC (6.1%)

Serious infections (6%)

Pain in extremity (5%)

Depression (5%)

Migraine (5%)

Pharyngitis (5%)

Pharyngitis (5%)

Cystitis (4%)

Leukopenia (4%)

Gastroenteritis viral (3%)

<1%

Anaphylaxis (0.6%)

Serious infusion reactions (0.5%) (ie, bradycardia, myalgia, headache, rash, urticaria, hypotension)

Postmarketing Reports

Fatal anaphylaxis

Contraindications

Hypersensitivity

Cautions

There were more deaths reported with belimumab than with placebo during the controlled period of the IV clinical trials in adults

Serious and sometimes fatal infections reported in patients receiving immunosuppressive agents; during clinical studies, more deaths and serious infections (eg, pneumonia, UTI, cellulitis, bronchitis) were reported with belimumab compared with placebo

Hypersensitivity reactions reported; delayed onset of acute hypersensitivity reactions observed; limited data suggest that patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk

Impact on development of malignancies is not known; as with other immunomodulating agents, the mechanism of action of belimumab could increase the risk for developing malignancies

Cases of progressive multifocal leukoencephalopathy (PML) resulting in neurological deficits reported in patients with SLE receiving immunosuppressants, including belimumab

Infusion-related effects were reported in patients administered IV belimumab; serious infusion reactions (eg, bradycardia, myalgia, headache, rash, urticaria, hypotension) reported

Depression and suicidality have been reported; monitor for new or worsening depression

Pregnancy

Healthcare professionals are encouraged to register patients by calling the pregnancy registry: at 1- (877) 681-6296

Data are insufficient to determine whether there is a drug-associated risk for major birth defects or miscarriage

There are risks to the mother and fetus associated with SLE, including worsening of the underlying disease, premature birth, spontaneous abortion, and intrauterine growth restriction

Lactation

Passage of maternal antiphospholipid antibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block

Monoclonal antibodies, such as belimumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero-exposed infant

Use during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus

Because maternal antibodies are excreted in human breast milk, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of breastfeeding to the infant and the importance of the drug to the mother

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 (IV); 108 mcg/mL (SC)

AUC: 3,083 days•mcg/mL (IV); 726 days•mcg/mL (SC)

Distribution

Vd (steady-state): 5 L

Half-life, distribution: 1.8 days (IV); 1.1 days (SC)

Elimination

Half-life, terminal: 19.4 days (IV); 18.3 days (SC)

Clearance: 215 mL/day (IV); 204 mL/day (SC)

IV Compatibilities

00.9% NaCl

0.45% NaCl

Lactated Ringer solution

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

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

Storage