Benlysta

Name: Benlysta

Benlysta Interactions

Formal drug interaction studies have not been performed. 

Tell your doctor about all the medicines you take including prescription and nonprescription medications, vitamins, and herbal supplements. 

Benlysta Overdose

If you use too much Benlysta, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If Benlysta is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if an overdose is suspected, seek emergency medical attention.

 

What is belimumab?

Belimumab is a monoclonal antibody that affects the actions of the body's immune system. Monoclonal antibodies are made to target and destroy only certain cells in the body. This may help to protect healthy cells from damage.

Belimumab is used to treat active systemic lupus erythematosus (SLE) in adults.

Belimumab is not for use in people who have severe kidney problems caused by SLE, or have active SLE that affects the central nervous system (brain, nerves, and spinal cord).

Belimumab may also be used for other purposes not listed in this medication guide.

What happens if I miss a dose?

Contact your doctor if you miss an appointment for your belimumab injection.

What other drugs will affect belimumab?

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with belimumab, especially:

  • cyclophosphamide (Cytoxan); or

  • drugs that weaken your immune system such as cancer medicine, steroids, and medicines to prevent rejection of a transplanted organ.

This list is not complete. Other drugs may interact with belimumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Interactions for Benlysta

No formal drug interaction studies to date.1

Vaccines

No data available on effects of immunization in patients receiving belimumab.1 Belimumab may interfere with immune response to vaccines.1

Avoid live vaccines during and within 30 days prior to initiation of belimumab therapy; safety not established.1 No data available on secondary transmission of infection by live vaccines in belimumab-treated patients.1

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Increased systemic clearance of belimumab1

Not considered clinically important1

Antimalarials (e.g., chloroquine, hydroxychloroquine)

No substantial effect on belimumab pharmacokinetics1 14 15

Corticosteroids

Increased systemic clearance of belimumab1

Not considered clinically important1

HMG-CoA reductase inhibitors (statins)

No substantial effect on belimumab pharmacokinetics1

Immunomodulatory and immunosuppressive agents

Possible increased risk of infection13

Azathioprine, methotrexate, mycophenolate: No substantial effect on belimumab pharmacokinetics1

Concomitant use of other biologic agents (e.g., B-cell-targeted therapies) or IV cyclophosphamide not recommended1

NSAIAs (including aspirin)

No substantial effect on belimumab pharmacokinetics1

Benlysta Dosage and Administration

Benlysta may be administered as an intravenous infusion or as a subcutaneous injection. Vials are intended for intravenous use only (not for subcutaneous use) and autoinjectors and prefilled syringes are intended for subcutaneous use only (not for intravenous use).

Intravenous Preparation and Dosing Instructions

Recommended Intravenous Dosage Regimen

Benlysta for intravenous use must be reconstituted and diluted prior to administration. Do not administer as an intravenous push or bolus.

The recommended intravenous dosage regimen is 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter. Reconstitute, dilute, and administer as an intravenous infusion over a period of 1 hour. The infusion rate may be slowed or interrupted if the patient develops an infusion reaction. The infusion must be discontinued immediately if the patient experiences a serious hypersensitivity reaction [see Contraindications (4), Warnings and Precautions (5.3)].

Premedication Recommendations prior to Intravenous Use

Prior to intravenous dosing with Benlysta, consider administering premedication for prophylaxis against infusion reactions and hypersensitivity reactions [see Warnings and Precautions (5.3, 5.4), Adverse Reactions (6.1)].

Preparation of Intravenous Solutions

Benlysta for intravenous use is provided as a lyophilized powder in a single‑dose vial and should be reconstituted and diluted by a healthcare professional using aseptic technique as follows. Use of a 21- to 25-gauge needle is recommended when piercing the vial stopper for reconstitution and dilution.

Reconstitution Instructions for Intravenous Use:

1. Remove the vial of Benlysta from the refrigerator and allow to stand for 10 to 15 minutes for the vial to reach room temperature. 2. Reconstitute the Benlysta powder with Sterile Water for Injection, USP, as follows. The reconstituted solution will contain a concentration of 80 mg/mL belimumab. • Reconstitute the 120-mg vial with 1.5 mL Sterile Water for Injection, USP. • Reconstitute the 400-mg vial with 4.8 mL Sterile Water for Injection, USP. 3. The stream of sterile water should be directed toward the side of the vial to minimize foaming. Gently swirl the vial 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 after the sterile water has been added, but it may take up to 30 minutes. Protect the reconstituted solution from sunlight. 4. If a mechanical reconstitution device (swirler) is used to reconstitute Benlysta, it should not exceed 500 rpm and the vial swirled for no longer than 30 minutes. 5. 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.

Dilution Instructions for Intravenous Use:

6. Dextrose intravenous solutions are incompatible with Benlysta. Benlysta should only be diluted in 0.9% Sodium Chloride Injection, USP (normal saline), 0.45% Sodium Chloride Injection, USP (half-normal saline), or Lactated Ringer’s Injection, USP to a volume of 250 mL for intravenous infusion. From a 250‑mL infusion bag or bottle of normal saline, half-normal saline, or Lactated Ringer’s Injection, withdraw and discard a volume equal to the volume of the reconstituted solution of Benlysta required for the patient’s dose. Then add the required volume of the reconstituted solution of Benlysta into the infusion bag or bottle. Gently invert the bag or bottle to mix the solution. Any unused solution in the vials must be discarded. 7. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard the solution if any particulate matter or discoloration is observed. 8. The reconstituted solution of Benlysta, if not used immediately, should be stored protected from direct sunlight and refrigerated at 2° to 8°C (36° to 46°F). Solutions of Benlysta diluted in normal saline, half-normal saline, or Lactated Ringer’s Injection may be stored at 2° to 8°C (36° to 46°F) or room temperature. The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours. 9. No incompatibilities between Benlysta and polyvinylchloride or polyolefin bags have been observed.

Administration Instructions for Intravenous Use

1. The diluted solution of Benlysta should be administered by intravenous infusion, over a period of 1 hour. 2. Benlysta should be administered by healthcare providers prepared to manage anaphylaxis [see Warnings and Precautions (5.3)]. 3. Benlysta should not be infused concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of Benlysta with other agents.

2.2 Subcutaneous Dosing Instructions

Recommended Subcutaneous Dosage Regimen

The recommended dosage is 200 mg once weekly given as a subcutaneous injection in the abdomen or thigh. Subcutaneous dosing is not based on weight.

If transitioning from intravenous therapy with Benlysta to subcutaneous administration, administer the first subcutaneous dose 1 to 4 weeks after the last intravenous dose.

Administration Instructions for Subcutaneous Injection

1. It is recommended that the first subcutaneous injection of Benlysta should be under the supervision of a healthcare professional. The healthcare provider should provide proper training in subcutaneous technique and education about signs and symptoms of hypersensitivity reactions [see Warning and Precautions (5.3)]. A patient may self-inject or the patient caregiver may administer Benlysta subcutaneously after the healthcare provider determines it is appropriate. 2. Instruct the patient or patient caregiver to follow the directions for administration provided in the Instructions for Use. 3. Instruct the 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 subcutaneous injection. Do not warm Benlysta in any other way. 4. Prior to administration, instruct the patient or patient caregiver to visually inspect the window of the autoinjector or the prefilled syringe for particulate matter or discoloration. Benlysta should be clear to opalescent and colorless to pale yellow. Do not use Benlysta if the product exhibits discoloration or particulate matter. Instruct the patient not to use the Benlysta autoinjector or prefilled syringe if dropped on a hard surface. 5. 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. 6. Instruct the patient to administer Benlysta 200 mg once a week, preferably on the same day each week. 7. If a dose is missed, instruct the patient to administer a 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. It is not recommended to administer 2 doses on the same day.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of belimumab.

Effects on male and female fertility have not been directly evaluated in animal studies.

Clinical Studies

Clinical Trials Experience with Intravenous Administration

The safety and effectiveness of Benlysta administered intravenously plus standard therapy were evaluated in 3 randomized, double‑blind, placebo‑controlled trials involving 2,133 patients with SLE according to the American College of Rheumatology criteria (Trials 1, 2, and 3). Patients with severe active lupus nephritis and severe active CNS lupus were excluded. Patients were on a stable standard therapy SLE treatment regimen comprising any of the following (alone or in combination): corticosteroids, antimalarials, NSAIDs, and immunosuppressives. Use of other biologics and intravenous cyclophosphamide were not permitted.

Trial 1: Benlysta 1 mg/kg, 4 mg/kg, 10 mg/kg

Trial 1 enrolled 449 patients and evaluated doses of 1, 4, and 10 mg/kg Benlysta plus standard therapy compared with placebo plus standard therapy over 52 weeks in patients with SLE. Patients had to have a Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score of >4 at baseline and a history of autoantibodies (anti-nuclear antibody [ANA] and/or anti-double-stranded DNA [anti-dsDNA]), but 28% of the population was autoantibody negative at baseline. The co-primary endpoints were percent change in SELENA-SLEDAI score at Week 24 and time to first flare over 52 weeks. No significant differences between any of the groups receiving Benlysta and the group receiving placebo were observed. Exploratory analysis of this trial identified a subgroup of patients (72%) who were autoantibody positive in whom Benlysta appeared to offer benefit. The results of this trial informed the design of Trials 2 and 3 and led to the selection of a target population and indication that is limited to autoantibody-positive SLE patients.

Trials 2 and 3: Benlysta 1 mg/kg and 10 mg/kg

Trials 2 and 3 were randomized, double‑blind, placebo‑controlled trials in patients with SLE that were similar in design except duration - Trial 2 (N = 819) was 76 weeks’ duration and Trial 3 (N = 865) was 52 weeks’ duration. Patients had active SLE disease with a SELENA‑SLEDAI score ≥6 and positive autoantibody test results at screening. Patients were excluded from the trial if they had ever received treatment with a B‑cell-targeted agent or if they were currently receiving other biologic agents. Intravenous cyclophosphamide was not permitted within the previous 6 months or during the trial. Trial 2 was conducted primarily in North America and Europe. Trial 3 was conducted in South America, Eastern Europe, Asia, and Australia.

Baseline concomitant medications included corticosteroids (Trial 2: 76%, Trial 3: 96%), immunosuppressives (Trial 2: 56%, Trial 3: 42%; including azathioprine, methotrexate, and mycophenolate), and antimalarials (Trial 2: 63%, Trial 3: 67%). Most patients (>70%) were receiving 2 or more classes of SLE medications.

In Trial 2 and Trial 3, more than 50% of patients had 3 or more active organ systems involved at baseline. The most common active organ systems at baseline based on SELENA-SLEDAI were mucocutaneous (82% in both trials), immune (Trial 2: 74%, Trial 3: 85%), and musculoskeletal (Trial 2: 73%, Trial 3: 59%). Less than 16% of patients had some degree of renal activity and less than 7% of patients had activity in the vascular, cardio-respiratory, or CNS systems.

At screening, patients were stratified by disease severity based on their SELENA‑SLEDAI score (≤9 vs. ≥10), proteinuria level (<2 g/24 h vs. ≥2 g/24 h), and race (African or Indigenous-American descent vs. other), and then randomly assigned to receive Benlysta 1 mg/kg, Benlysta 10 mg/kg, or placebo in addition to standard therapy. The patients were administered trial medication intravenously over a 1‑hour period on Days 0, 14, 28, and then every 28 days for 48 weeks in Trial 3 and for 72 weeks in Trial 2.

The primary efficacy endpoint was a composite endpoint (SLE Responder Index-4 or SRI-4) that defined response as meeting each of the following criteria at Week 52 compared with baseline:

• ≥4‑point reduction in the SELENA‑SLEDAI score, and • no new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores, and • no worsening (<0.30‑point increase) in Physician’s Global Assessment (PGA) score.

The SRI uses the SELENA‑SLEDAI score as an objective measure of reduction in global disease activity; the BILAG index to ensure no significant worsening in any specific organ system; and the PGA to ensure that improvements in disease activity are not accompanied by worsening of the patient’s condition overall.

In both Trials 2 and 3, the proportion of patients with SLE achieving an SRI-4 response, as defined for the primary endpoint, was significantly higher in the group receiving Benlysta 10 mg/kg plus standard therapy than in the group receiving placebo plus standard therapy. The effect on the SRI-4 was not consistently significantly different for patients receiving Benlysta 1 mg/kg plus standard therapy relative to placebo plus standard therapy in both trials. The 1-mg/kg dose is not recommended. The trends in comparisons between the treatment groups for the rates of response for the individual components of the endpoint were generally consistent with that of the SRI-4 (Table 4). At Week 76 in Trial 2, the SRI-4 response rate with Benlysta 10 mg/kg was not significantly different from that of placebo (39% and 32%, respectively).

Table 4. Clinical Response Rate in Patients with SLE after 52 Weeks of Treatment
Trial 2 Trial 3
a Patients dropping out of the trial early or experiencing certain increases in background medication were considered as failures in these analyses. In both trials, a higher proportion of placebo patients were considered as failures for this reason compared with the groups receiving Benlysta.
b The 1-mg/kg dose is not recommended.

Response

Placebo +

Standard Therapy

(n = 275)

Benlysta

1 mg/kg + Standard Therapyb

(n = 271)

Benlysta

10 mg/kg + Standard Therapy

(n = 273)

Placebo +

Standard Therapy

(n = 287)

Benlysta

1 mg/kg + Standard Therapyb

(n = 288)

Benlysta

10 mg/kg + Standard Therapy

(n = 290)

SLE Responder Index-4 (SRI-4)a

34%

41%

(P = 0.104)

43%

(P = 0.021)

44%

51%

(P = 0.013)

58%

(P <0.001)

Odds Ratio

(95% CI) vs. placebo

1.3

(0.9, 1.9)

1.5

(1.1, 2.2)

1.6

(1.1, 2.2)

1.8

(1.3, 2.6)

Components of SLE Responder Index-4 (SRI-4)

Percent of patients with reduction in SELENA-SLEDAI ≥4

36%

43%

47%

46%

53%

58%

Percent of patients with no worsening by BILAG index

65%

75%

69%

73%

79%

81%

Percent of patients with no worsening by PGA

63%

73%

69%

69%

79%

80%

The reduction in disease activity seen in the SRI-4 was related primarily to improvement in the most commonly involved organ systems; namely, mucocutaneous, musculoskeletal, and immune.

Effect in Black/African-American Patients

Exploratory sub-group analyses of SRI-4 response rate in black patients (n = 148) were performed. The SRI-4 response rate in black patients in groups receiving Benlysta plus standard therapy was less than that in the group receiving placebo plus standard therapy (22/50 or 44% for placebo, 15/48 or 31% for Benlysta 1 mg/kg, and 18/50 or 36% for Benlysta 10 mg/kg). Although no definitive conclusion can be drawn from this subgroup analysis, caution should be used when considering treatment with Benlysta in black/African-American patients.

Effect on Concomitant Steroid Treatment

In Trial 2 and Trial 3, 46% and 69% of patients, respectively, were receiving prednisone at doses >7.5 mg/day at baseline. The proportion of patients able to reduce their average prednisone dose by at least 25% to ≤7.5 mg/day during Weeks 40 through 52 was not consistently significantly different for Benlysta plus standard therapy relative to placebo plus standard therapy in both trials. In Trial 2, 17% of patients receiving Benlysta 10 mg/kg plus standard therapy and 19% of patients receiving Benlysta 1 mg/kg plus standard therapy achieved this level of steroid reduction compared with 13% of patients receiving placebo plus standard therapy. In Trial 3, 19%, 21%, and 12% of patients receiving Benlysta 10 mg/kg, Benlysta 1 mg/kg, and placebo, respectively, plus standard therapy achieved this level of steroid reduction.

Effect on Severe SLE Flares

The probability of experiencing a severe SLE flare, as defined by a modification of the SELENA Trial flare criteria, which excluded severe flares triggered only by an increase of the SELENA-SLEDAI score to >12, was calculated for both Trials 2 and 3. The proportion of patients having at least 1 severe flare over 52 weeks was not consistently significantly different for Benlysta plus standard therapy relative to placebo plus standard therapy in both trials. In Trial 2, 18% of patients receiving Benlysta 10 mg/kg plus standard therapy and 16% of patients receiving Benlysta 1 mg/kg plus standard therapy had a severe flare compared with 24% of patients receiving placebo plus standard therapy. In Trial 3, 14%, 18%, and 23% of patients receiving Benlysta 10 mg/kg, Benlysta 1 mg/kg and placebo, respectively, plus standard therapy had a severe flare.

Clinical Trials Experience with Subcutaneous Administration

The safety and effectiveness of Benlysta administered subcutaneously were evaluated in a randomized, double‑blind, placebo‑controlled trial involving 836 patients with SLE according to the American College of Rheumatology criteria (Trial 4). Patients with severe active lupus nephritis and severe active CNS lupus were excluded. The trial (2:1 randomization) evaluated Benlysta 200 mg once weekly plus standard therapy (n = 556) compared with placebo once weekly plus standard therapy (n = 280) over 52 weeks in patients with active SLE disease. Patients had to have a SELENA-SLEDAI score of ≥8 and positive autoantibody test (anti-nuclear antibody [ANA] and/or anti-double-stranded DNA [anti-dsDNA] results at screening.

No significant differences in baseline patient characteristics were observed between treatment groups. In some countries, treatment with a B-cell-targeted agent was permitted if received a year or more prior to baseline, otherwise, treatment with a B-cell-targeted agent was not permitted. Patients were excluded from the trial if they were currently receiving other biologic agents. Anti-tumor necrosis factor therapy, intravenous cyclophosphamide, interleukin-1 receptor antagonist, intravenous immunoglobulin (IVIG), prednisone >100 mg/day, and plasmapheresis were not permitted within the previous 3 months or during the trial. The trial was conducted in North America, South America, Europe, and Asia. Baseline concomitant medications included corticosteroids (86%), antimalarials (69%), and immunosuppressives (46% including azathioprine, methotrexate, and mycophenolate). Most patients (approximately 80%) were receiving 2 or more classes of SLE medications.

More than 50% of patients had 3 or more active organ systems involved at baseline. The most common active organ systems at baseline based on SELENA-SLEDAI were mucocutaneous (88%), musculoskeletal (78%), and immunologic (76%). Overall, 12% of patients had some degree of renal activity and less than 15% of patients had activity in the vascular, cardio-respiratory, or CNS systems. Patients were stratified by disease severity based on their SELENA-SLEDAI score (≤9 vs. ≥10), complement level (C3 and/or C4 low vs. other), and race (black vs. other), and then randomly assigned to receive Benlysta 200 mg plus standard therapy or placebo once weekly plus standard therapy.

The primary efficacy endpoint was the SLE Responder Index-4 (SRI-4) at Week 52 as described in the intravenous trials. Secondary efficacy endpoints included time to first severe flare (as measured by the modified SELENA-SLEDAI SLE Flare Index) and the proportion of patients receiving prednisone >7.5 mg/day at baseline whose average prednisone dose had been reduced by ≥25% to ≤7.5 mg/day during Weeks 40 through 52.

The proportion of patients achieving an SRI-4 response was significantly higher in patients receiving Benlysta plus standard therapy compared with placebo plus standard therapy. The trends comparing the treatment groups with respect to the probability of response for the individual components of the endpoint were consistent with that of the SRI-4 (Table 5).

Table 5. Clinical Response Rate in Patients with SLE after 52 Weeks of Treatment
a Patients dropping out of the trial early or experiencing certain increases in background medication were considered as failures in these analyses. A higher proportion of patients receiving placebo plus standard therapy were considered as failures for this reason compared with the group receiving Benlysta plus standard therapy.

Response

Placebo +

Standard Therapy

(n = 279)

Benlysta +

Standard Therapy

(n = 554)

SLE Responder Index-4(SRI-4)a

48%

61%

P = 0.0006

Odds Ratio

(95% CI) vs. placebo

1.7

(1.3, 2.3)

Components of SLE Responder Index-4 (SRI-4)

Percent of patients with reduction in SELENA-SLEDAI ≥4

49%

62%

Percent of patients with no worsening by BILAG index

74%

81%

Percent of patients with no worsening by PGA

73%

81%

The reduction in disease activity seen in the SRI-4 was related primarily to improvement in the most commonly involved organ systems, namely, mucocutaneous, musculoskeletal, immunologic, and vascular.

The proportion of SRI-4 responders by visit through Week 52 is shown in Figure 1.

Figure 1. Proportion (%) of SRI-4 Responders (+/- Standard Error) by Visita

a The same patients may not have responded at each timepoint.

Effect in Black/African-American Patients

Exploratory sub-group analyses of SRI-4 response rate in black patients (n = 91) were performed. The SRI-4 response rate was slightly higher in black patients receiving Benlysta plus standard therapy (26/58 or 45%) compared with the group receiving placebo plus standard therapy (13/33 or 39%), but the treatment difference was not as large as that observed in the overall population and no definitive conclusion can be drawn from this subgroup analysis. Caution should be used when considering treatment with Benlysta in black/African-American patients.

Effect on Concomitant Steroid Treatment

At baseline, 60% of patients were receiving prednisone at doses >7.5 mg/day. Among these patients, 18% of patients receiving Benlysta plus standard therapy reduced their average prednisone dose by at least 25% to ≤7.5 mg/day during Weeks 40 through 52 compared with 12% of patients on placebo plus standard therapy; this difference was not statistically significant (OR = 1.65 [95% CI: 0.95, 2.84]).

Effect on Severe SLE Flares

The probability of experiencing a severe SLE flare, as measured by the modified SELENA-SLEDAI SLE Flare Index, excluding severe flares triggered only by an increase of the SELENA-SLEDAI score to >12, was calculated. The proportion of patients reporting at least 1 severe flare during the study was lower in patients treated with Benlysta plus standard therapy (11%) compared with those receiving placebo plus standard therapy (18%). Patients treated with Benlysta plus standard therapy had a 49% lower risk of experiencing at least 1 severe flare during the 52 weeks of observation, relative to the patients receiving placebo plus standard therapy (HR = 0.51 [95% CI: 0.35, 0.74]). Of the patients experiencing a severe flare, the median time to the first severe flare was delayed in patients receiving Benlysta plus standard therapy compared with placebo plus standard therapy (171 days vs. 118 days).

How Supplied/Storage and Handling

Intravenous Infusion

Benlysta (belimumab) for injection is a sterile, preservative-free, lyophilized powder for reconstitution and dilution prior to intravenous infusion provided in single-dose glass vials with a rubber stopper (not made with natural rubber latex) and a flip-off seal. Each 5-mL vial contains 120 mg of belimumab. Each 20-mL vial contains 400 mg of belimumab.

Benlysta vials are supplied as follows:

120 mg belimumab in a 5-mL single-dose vial (NDC 49401-101-01)

400 mg belimumab in a 20-mL single-dose vial (NDC 49401-102-01)

Refrigerate vials at 2° to 8°C (36° to 46°F). Store vials in the original carton until use to protect from light. Do not freeze. Avoid exposure to heat.

For Subcutaneous Injection

Benlysta (belimumab) injection is a clear to opalescent, and colorless to pale yellow solution for subcutaneous use. Each single-dose prefilled autoinjector or single-dose prefilled syringe is designed to deliver 200 mg of belimumab in 1 mL of solution and is supplied as follows:

200 mg/mL single-dose prefilled autoinjector with 27-gauge, half-inch needle attached (NDC 49401-088-01) in a carton of 4 (NDC 49401-088-35).

200 mg/mL single-dose prefilled glass syringe with 27-gauge, half-inch needle attached (NDC 49401-088-42) in a carton of 4 (NDC 49401-088-47).

Refrigerate prefilled autoinjectors and prefilled syringes at 2°C to 8°C (36°F to 46°F). Keep the product in the original carton to protect from light until the time of use. Do not freeze. Do not shake. Avoid exposure to heat.

Benlysta may be stored outside of the refrigerator up to 86°F (30°C) for up to 12 hours in the original container. Do not use and do not place back in refrigerator if left out for more than 12 hours.

What is Benlysta?

Benlysta (belimumab) is a monoclonal antibody that affects the actions of the body's immune system. Monoclonal antibodies are made to target and destroy only certain cells in the body. This may help to protect healthy cells from damage.

Benlysta is used to treat active systemic lupus erythematosus (SLE) in adults.

Benlysta is not for use in people who have severe kidney problems caused by SLE, or have active SLE that affects the central nervous system (brain, nerves, and spinal cord).

What should I avoid while receiving Benlysta?

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

Do not receive a "live" vaccine while using Benlysta. 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.

For Healthcare Professionals

Applies to belimumab: intravenous powder for injection

General

The most common adverse events were infections, headache, infusion reactions, arthralgia, nausea, hypersensitivity reactions, diarrhea, urinary tract infection, and pyrexia.[Ref]

Immunologic

Very common (10% or more): Infections (non-opportunistic) (70%)
Common (1% to 10%): Serious infections, pharyngitis, cystitis, gastroenteritis viral, anti-belimumab (the active ingredient contained in Benlysta) antibodies
Uncommon (0.1% to 1%): Infections resulting in death
Frequency not reported: Progressive multifocal leukoencephalopathy[Ref]

Hypersensitivity

Very common (10% or more): Infusion-related reactions (17%), hypersensitivity reactions (13%)
Uncommon (0.1% to 1%): Serious infusion reaction, anaphylaxis, angioedema
Rare (less than 0.1%): Delayed-type non-acute hypersensitivity reactions
Postmarketing reports: Fatal anaphylaxis[Ref]

-Hypersensitivity reaction covers a group of terms, including anaphylaxis, and symptoms including hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea.
-Infusion-related reaction covers a group of terms including bradycardia, myalgia, headache, rash, urticaria, pyrexia, hypotension, hypertension, dizziness, and arthralgia.
-Delayed-type, non- acute hypersensitivity reactions included rash, nausea, fatigue, myalgia, headache, and facial edema.[Ref]

Nervous system

Very common (10% or more): Headache (21.1%)
Common (1% to 10%): Migraine, fatigue[Ref]

Respiratory

Very common (10% or more): Upper respiratory tract infection (17.5%)
Common (1% to 10%): Nasopharyngitis, bronchitis[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia (16.2%)
Common (1% to 10%): Pain in extremity[Ref]

Gastrointestinal

Very common (10% or more): Nausea (15%), diarrhea (12%)[Ref]

Genitourinary

Very common (10% or more): Urinary tract infection
Common (1% to 10%): Cystitis[Ref]

Other

Very common (10% or more): Pyrexia (10%)
Common (1% to 10%): Fatigue
Uncommon (0.1% to 1%): Death[Ref]

Psychiatric

Common (1% to 10%): Insomnia, depression, anxiety
Uncommon (0.1% to 1%): Serious depression, suicide[Ref]

Hematologic

Common (1% to 10%): Leukopenia[Ref]

Oncologic

Uncommon (0.1% to 1%): Malignancies[Ref]

Dermatologic

Uncommon (0.1% to 1%): Rash, urticaria[Ref]

Some side effects of Benlysta may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

(web3)