Dosing and uses of Benlysta (belimumab)
Adult dosage forms and strengths
IV solution
- 120mg/vial
- 400mg/vial
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
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
10 mg/kg IV q2Weeks x3 doses,
Maintenance: 10 mg/kg IV q4Weeks
Administration
Reconstitute, dilute and administer as an IV infusion only, over a period of 1 hour
Consider administering premedication (ie, antihistamines, corticosteroids) for prophylaxis against infusion reactions and hypersensitivity reactions
Pediatric dosage forms and strengths
Safety and efficacy not established
Benlysta (belimumab) adverse (side) effects
>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%)
Serious infections (6%)
Pain in extremity (5%)
Depression (5%)
Migraine (5%)
Pharyngitis (5%)
<1%
Anaphylaxis (0.6%)
Serious infusion reactions (0.5%) (ie, bradycardia, myalgia, headache, rash, urticaria, hypotension)
Postmarketing Reports
Fatal anaphylaxis
Warnings
Contraindications
Hypersensitivity
Cautions
Serious and sometimes fatal infections have been 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, including anaphylaxis and death, have been reported; delayed onset of acute hypersensitivity reactions has been 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, including fatal cases, have been reported in patients with SLE receiving immunosuppressants, including belimumaB
Depression and suicidality have been reported; monitor for new or worsening depression
May decrease response to immunizations; do not administer live vaccines 30 days before or concurrently with belimumaB
Pregnancy and lactation
Pregnancy category: C
Pregnancy Registry: (877) 681-6296
Use during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus; women of childbearing potential should use adequate contraception during treatment and for at least 4 months after the final treatment
Lactation: unknown whether distributed in breast milk
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
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Benlysta (belimumab)
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
Storage
Unopened 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 vials
- If not used immediately, may be stored refrigerated 2-8°C (36-46°F)
- For single use only; discard any unused portion
Diluted 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
