Benlysta

Anti-Rheumatic Monoclonal Antibodies
B Lymphocyte Stimulator (BLyS) Inhibitors

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Vials are intended for intravenous use only (not subcutaneous use).
 
Reconstitution of Vial
Remove drug vial from the refrigerator and allow 10 to 15 minutes for it to reach room temperature.
Use a 21- or 25- gauge needle to pierce the vial stopper for reconstitution and dilution.
Reconstitute with the appropriate amount of Sterile Water for Injection to a final concentration of belimumab 80 mg/mL:
add 1.5 mL of Sterile Water for Injection to the 120-mg vial
add 4.8 mL of Sterile Water for Injection to the 400-mg vial
Direct the stream of Sterile Water for Injection toward the side of the vial to minimize foaming. Gently swirl for 60 seconds. Allow the vial to sit at room temperature during reconstitution, gently swirling the vial for 60 seconds every 5 minutes until the powder is dissolved. Do NOT shake. Reconstitution is typically complete within 10 to 15 minutes, but may take up to 30 minutes.
If a mechanical reconstitution device (swirler) is used to reconstitute belimumab, it should not exceed 500 rpm, and the vial swirled for no longer than 30 minutes.
Once reconstitution is complete, the solution should be opalescent and colorless to pale yellow, and without particles. Small air bubbles, however, are expected and acceptable.
Storage: Protect the reconstituted vial solution from sunlight. If not used immediately, refrigerate at 2 to 8 degrees C (36 to 46 degrees F). The total time from reconstitution to completion of infusion should not exceed 8 hours.[43658]
 
Preparation of the IV infusion
Once reconstituted, the belimumab injection in the vial must be further diluted to prepare the IV infusion.
Belimumab is NOT compatible with dextrose-containing solutions. Dilute belimumab in 0.9% Sodium Chloride Injection, 0.45% Sodium Chloride Injection, or Lactated Ringer's Injection only, to a total volume of 250 mL. For patients weighing 40 kg or less, a 100 mL bag or bottle of the above listed diluents may be used as long as the infusion concentration does not exceed 4 mg/mL.
From a 250 mL (or 100 mL) infusion bag or bottle, withdraw and discard a volume equal to the volume of the reconstituted solution of belimumab required for the patient's dose.
Then add the reconstituted solution of belimumab to the infusion bag or bottle.
Gently invert the bag or bottle to mix the solution. Do NOT shake.
Discard any unused belimumab solution that remains in the vials.
Storage: Once diluted, the IV infusion may be stored at 2 to 8 degrees C (36 to 46 degrees F) or room temperature. The total time from reconstitution to completion of infusion should not exceed 8 hours.[43658]
 
IV Infusion Administration
Administer belimumab by intravenous infusion only; do not give as an IV push or bolus.
Only health care providers prepared to manage anaphylaxis should administer belimumab by infusion.
Consider administering premedication for prophylaxis against infusion reactions and hypersensitivity reactions.
Infuse over 1 hour; administration may be slowed or interrupted if infusion reaction occurs.
Do not administer belimumab concomitantly in the same IV line with other agents.[43658]

Use only belimumab prefilled syringes or autoinjectors for subcutaneous administration (not vials).
The first belimumab subcutaneous injection should be under the supervision of a health care professional. Patients may self-administer belimumab using the prefilled syringe or autoinjector after proper training.
Both the prefilled syringe and autoinjector come with 'Instructions for Use'.
 
Preparation
Remove prefilled syringe or autoinjector from the refrigerator and allow 30 minutes to reach room temperature. Do not warm in any other way.
Inspect syringe or autoinjector prior to administration; belimumab should be clear to opalescent and colorless to pale yellow. Small air bubbles, however, are expected and acceptable.
Do not use the autoinjector or prefilled syringe if it is dropped on a hard surface.
Do NOT shake.
Storage of unopened prefilled syringes or autoinjectors: Protect from light and store refrigerated at 2 to 8 degrees C (36 to 46 degrees F) until time of use. Prefilled syringe or autoinjector may be stored outside the refrigerator for up to 12 hours if protected from light. Do not use or place back in the refrigerator if left out for more than 12 hours. Do not freeze and do not use if the injection has been frozen. Do not shake. Avoid exposure to heat.[43658]
 
Subcutaneous Administration
Subcutaneous administration sites include the abdomen and thigh. Do not inject within 2 inches of the umbilicus. Do not administer where the skin is tender, bruised, erythematous, or hard.
For the prefilled syringe: Do not remove the needle cap until just prior to injection. Insert the entire needle into the pinched area of the skin at a slight 45-degree angle using a dart-like motion. Push the plunger all the way down until all the solution is injected. While keeping your hold on the syringe, slowly move your thumb back, allowing the plunger to rise. The needle will automatically rise into the needle guard.
For the autoinjector: Do not remove the ring cap until just prior to injection. Position the autoinjector straight over the injection site at a 90-degree angle. Make sure the gold needle guard is flat on the skin. To start the injection, firmly press the autoinjector down onto the injection site and hold in place. A "click" will be heard at the start of the injection. Continue to hold the autoinjector down until you see that the purple indicator has stopped moving. A second "click" may be heard. The injection may take up to 15 seconds to complete. When the injection is complete, lift the injector from the injection site.
Properly dispose of any used prefilled syringes or autoinjectors immediately after use.
Rotate sites of injection with each dose. When a 400-mg dose is administered at the same site, the 2 individual 200-mg injections should be administered at least 5 cm (approximately 2 inches) apart.
Missed dose: If a dose is missed, administer as soon as possible. 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. Do not give 2 doses on the same day.[43658]

infection / Delayed / 3.7-14.0
suicidal ideation / Delayed / 1.3-2.4
angioedema / Rapid / 0.6-0.6
anaphylactic shock / Rapid / 0.6-0.6
bradycardia / Rapid / 0.5-0.5
new primary malignancy / Delayed / 0.2-0.4
leukoencephalopathy / Delayed / Incidence not known
skin cancer / Delayed / Incidence not known

infusion-related reactions / Rapid / 17.0-17.0
depression / Delayed / 2.7-6.3
migraine / Early / 5.0-5.0
antibody formation / Delayed / 0-4.8
leukopenia / Delayed / 4.0-4.0
cystitis / Delayed / 4.0-4.0
hypotension / Rapid / 0.6-0.6
dyspnea / Early / 0.6-0.6
edema / Delayed / Incidence not known
hematoma / Early / Incidence not known
erythema / Early / Incidence not known

nausea / Early / 15.0-15.0
diarrhea / Early / 12.0-12.0
fever / Early / 10.0-10.0
pharyngitis / Delayed / 5.0-9.0
injection site reaction / Rapid / 6.1-6.1
insomnia / Early / 6.0-6.0
anxiety / Delayed / 3.9-3.9
myalgia / Early / 0.5-0.5
influenza / Delayed / 5.0
sinusitis / Delayed / 5.0
headache / Early / 3.0
pruritus / Rapid / 3.0
rash / Early / 3.0
urticaria / Rapid / 3.0
fatigue / Early / Incidence not known

Benlysta, Benlysta SC

Rx

Intravenous and subcutaneous human monoclonal antibody that inhibits B lymphocyte stimulator (BLyS)
Used with standard therapy for active systemic lupus erythematosus (SLE) and active lupus nephritis in adult and pediatric patients 5 years and older
Infusion reactions possible with IV use; serious hypersensitivity reactions and infections have been reported

10 mg/kg/dose IV infused over 1 hour every 2 weeks for the first 3 doses, then every 4 weeks thereafter. Consider premedication to attenuate infusion- and hypersensitivity-related reactions. Discontinue the infusion immediately if the patient experiences a serious hypersensitivity reaction.[43658]

10 mg/kg/dose IV infused over 1 hour every 2 weeks for the first 3 doses, then every 4 weeks thereafter. Consider premedication to attenuate infusion- and hypersensitivity-related reactions. Discontinue the infusion immediately if the patient experiences a serious hypersensitivity reaction.[43658]

200 mg subcutaneously once weekly. If transitioning from IV to subcutaneous therapy, administer the first subcutaneous dose 1 to 4 weeks after the last IV dose.[43658]

10 mg/kg/dose IV infused over 1 hour every 2 weeks for the first 3 doses, then every 4 weeks thereafter. Consider premedication to attenuate infusion- and hypersensitivity-related reactions. Discontinue the infusion immediately if the patient experiences a serious hypersensitivity reaction.

10 mg/kg/dose IV infused over 1 hour every 2 weeks for the first 3 doses, then every 4 weeks thereafter. Consider premedication to attenuate infusion- and hypersensitivity-related reactions. Discontinue the infusion immediately if the patient experiences a serious hypersensitivity reaction.

400 mg (two 200-mg injections) subcutaneously once weekly for 4 doses, then 200 mg subcutaneously once weekly thereafter. A patient may transition from intravenous (IV) to subcutaneous therapy any time after receipt of the first 2 IV doses. If transitioning from IV to subcutaneous therapy, administer the first subcutaneous dose of 200 mg 1 to 2 weeks after the last IV dose.

No dosage adjustments are needed.

No dosage adjustments are needed.

Anifrolumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including belimumab. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cyclophosphamide: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as intravenous cyclophosphamide. Therefore, belimumab use is not recommended in combination with intravenous cyclophosphamide. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Live Vaccines: (Major) Live vaccines should not be given for 30 days before or concurrently with belimumab, as clinical safety has not been established. Because of its mechanism of action, belimumab may interfere with the response to immunizations. No data are available on the secondary transmission of infection from persons receiving live vaccines. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Ocrelizumab: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as ocrelizumab. Therefore, belimumab use is not recommended in combination with biologic therapies. Potential concerns with use together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Ofatumumab: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as ofatumumab. Therefore, belimumab use is not recommended in combination with biologic therapies. Potential concerns with use together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Rituximab: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including rituximab. Therefore, belimumab use is not recommended in combination with biologic therapies. Potential concerns with use together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Rituximab; Hyaluronidase: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including rituximab. Therefore, belimumab use is not recommended in combination with biologic therapies. Potential concerns with use together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tumor Necrosis Factor modifiers: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Therefore, belimumab use is not recommended in combination with TNF blockers. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.

Benlysta Intravenous Inj Pwd F/Sol: 120mg, 400mg
Benlysta SC Subcutaneous Inj Sol: 1mL, 200mg

10 mg/kg/dose IV; 200 mg/week subcutaneously.

10 mg/kg/dose IV; 200 mg/week subcutaneously.

10 mg/kg/dose IV; safety and efficacy of subcutaneous administration have not been established.

5 to 12 years: 10 mg/kg/dose IV; safety and efficacy of subcutaneous administration have not been established.
1 to 4 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Belimumab inhibits B lymphocyte stimulator (BLyS), which is a B-cell survival factor. Normally, the soluble BLyS binds to its receptors on B cells and allows B cell survival. Belimumab binds BLyS and prevents it from binding to its receptors on B cells. Thus, the survival of B cells including autoreactive B cells is inhibited by belimumab. Further, the differentiation of B cells into immunoglobulin-producing plasma cells is reduced.
 
Receipt of belimumab infusions for 52 weeks to patients with systemic lupus erythematosus (SLE) significantly reduced circulating CD19+, CD20+, naive, and activated B cells, plasmacytoid cells, and the SLE B-cell subset. Reductions in naive and the SLE B-cell subset were observed as early as week 8 and were sustained to week 52. Memory cells increased initially and slowly declined toward baseline concentrations by week 52. The clinical relevance of these effects on B cells has not been established. Receipt of belimumab also led to reductions in IgG and anti-dsDNA and to increases in complement (C3 and C4) as early as week 8 and were sustained through week 52. The clinical relevance of normalizing these biomarkers has not been definitively established.

Belimumab is administered by intravenous infusion or subcutaneous injection. Volume of distribution in adults is 5 L. Systemic clearance is approximately 204 to 215 mL/day, and terminal half-life is 18.3 to 19.4 days.[43658]
 
Affected cytochrome P450 (CYP450) enzymes and drug transporters: Unknown

Cmax and AUC were 313 mcg/mL and 3,083 mcg/mL x day, respectively, and the distribution half-life was 1.8 days after receipt of a 10 mg/kg IV infusion in adult patients.[43658]

After subcutaneous administration of 200 mg belimumab in SLE patients, the time to maximum concentration was 2.6 days. The bioavailability is approximately 74%. With weekly administration, there were minor fluctuations around the average concentration with the minimum concentration being only slightly below the average concentration (104 mcg/mL). Cmax and AUC were 108 mcg/mL and 726 mcg/mL x day, respectively, with a distribution half-life of 1.1 days. Population pharmacokinetic modeling and simulation of the subcutaneous belimumab 400 mg weekly loading dose predicted an average belimumab concentration of 78 mcg/mL during the first 12-weeks, which is similar to the estimated concentration of 89 mcg/mL for intravenous administration. The loading dose of 400 mg weekly results in steady-state concentrations from week 2 of dosing. In adults with lupus nephritis, average steady-state concentrations with subcutaneous belimumab 200 mg once weekly are predicted to be similar to observed concentrations with belimumab 10 mg/kg intravenously every 4 weeks.[43658]

Limited data on use of belimumab during human pregnancy, either from observational studies, published case reports, or postmarketing surveillance, are insufficient to determine whether there is a drug-associated risk for major birth defects or miscarriage. 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 fetus. There are also risks to the mother and fetus associated with the underlying maternal condition, systemic lupus erythematosus (SLE). There is 1 case report published of belimumab use throughout pregnancy in a mother with SLE; use led to well-controlled SLE in the mother, but with the presence of mild Ebstein's anomaly of the heart in the baby. During animal studies, no evidence of embryotoxicity or fetal malformations were noted when monkeys were exposed to approximately 9 times (based on intravenous administration) and 20 times (based on subcutaneous administration) the maximum recommended human dose (MRHD). Belimumab-related findings in monkey fetuses and/or infant monkeys included reduction in B-cell counts, reductions in the density of lymphoid tissue B-lymphocytes in the spleen and lymph nodes, and altered IgG and IgM titers. These findings were reversible within 3 to 12 months after the drug was discontinued. Based on these data, the immune system of neonates or infants of treated mothers may be adversely affected; the risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to belimumab in utero. Monitor an infant of a belimumab-treated mother for B-cell reduction and other immune dysfunction after birth. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to belimumab; information about the registry can be obtained at https://mothertobaby.org/ongoing-study/benlysta-belimumab/ or by calling 1-877-311-8972.