Benlysta Side Effects Center

Last updated on RxList: 8/8/2022
Benlysta Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Benlysta?

Benlysta (belimumab) is a monoclonal antibody indicated for the treatment of adult patients with active systemic lupus erythematosus (SLE). Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.

What Are Side Effects of Benlysta?

Common side effects of Benlysta include:

Tell your doctor if you have any serious side effects, including:

  • mental/mood/behavior changes (such as new or worsening depression, anxiety, thoughts of suicide, or thoughts about hurting yourself or others),
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling,
  • wheezing, chest tightness, trouble breathing, or
  • signs of cancer (such as fever, night sweats, unusual tiredness, unexplained weight loss, swollen glands, and unusual lumps or growths).

Benlysta can cause serious and sometimes fatal side effects such as infections, and heart problems.

Benlysta may cause serious side effects including:

  • hives,
  • difficulty breathing,
  • swelling of your face, lips, tongue, or throat,
  • anxiety,
  • lightheadedness,
  • nausea,
  • itching,
  • severe headache,
  • skin redness and swelling,
  • fever,
  • chills,
  • cough with mucus,
  • pain or burning when you urinate,
  • urinating more than usual,
  • bloody diarrhea,
  • new or worsening depression,
  • mood or behavior changes,
  • trouble sleeping,
  • risk-taking behavior,
  • thoughts about hurting yourself or others,
  • wheezing,
  • chest tightness,
  • trouble breathing,
  • chest pain or pressure,
  • pain spreading to your jaw or shoulder, and
  • sweating

Get medical help right away if you have any of the symptoms listed above.

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Benlysta

The recommended dosage regimen for Benlysta is 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter.

What Drugs, Substances, or Supplements Interact with Benlysta?

Formal drug interaction studies have not been performed with Benlysta.

Benlysta During Pregnancy and Breastfeeding

Before you receive Benlysta, tell your healthcare provider if you are pregnant or plan to become pregnant. It is not known if Benlysta will harm your unborn baby. Tell your healthcare provider if you become pregnant during your treatment with Benlysta. Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Benlysta passes into your breast milk. You and your healthcare provider should decide if you will receive Benlysta or breastfeed. You should not do both.

Additional Information

Our Benlysta (belimumab) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Lupus Symptoms, Rash, and Treatment See Slideshow
Benlysta Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives, itching; feeling anxious or light-headed; difficult breathing; swelling of your face, lips, tongue, or throat.

Some people have had serious or fatal allergic reactions to this medicine within hours or days after an injection. Tell your doctor right away if you have symptoms such as muscle pain, headache, tiredness, slow heartbeats, rash, itching, swelling in your face or throat, anxiety, nausea, trouble breathing, and feeling dizzy or light-headed.

You may get infections more easily, even serious or fatal infections. Stop using belimumab and call your doctor right away if you have signs of infection such as:

  • fever, chills;
  • skin sores, warmth, or redness;
  • cough with mucus, chest pain, shortness of breath;
  • pain or burning when you urinate;
  • urinating more than usual; or
  • bloody diarrhea.

Belimumab may cause a serious brain infection that can lead to disability or death. Call your doctor right away if you have problems with speech, thought, vision, or muscle movement. These symptoms may start gradually and get worse quickly.

Also call your doctor at once if you have new or worsening depression, anxiety, mood or behavior changes, trouble sleeping, risk-taking behavior, or thoughts about hurting yourself or others.

Common side effects may include:

  • nausea, diarrhea;
  • fever, sore throat, runny or stuffy nose, cough, chest tightness;
  • pain, itching, redness, or swelling where an injection was given under the skin;
  • pain in your arms or legs;
  • headache, depressed mood; or
  • sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

Lupus is an infection. See Answer
Benlysta Professional Information

SIDE EFFECTS

The following serious adverse reactions are described below and in the Warnings and Precautions section:

  • Serious Infections [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions, including Anaphylaxis [see WARNINGS AND PRECAUTIONS]
  • Depression and Suicidality [see WARNINGS AND PRECAUTIONS]
  • Malignancy [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials With Intravenous Administration In Adult And Pediatric Patients

Adult Patients With SLE

The data described in Table 1 reflect exposure to BENLYSTA administered intravenously plus standard therapy compared with placebo plus standard therapy in 2,133 adult patients with SLE in 3 controlled trials (Trials 1, 2, and 3). Patients received BENLYSTA plus standard therapy at doses of 1 mg/kg (n = 673), 4 mg/kg (n = 111; Trial 1 only), or 10 mg/kg (n = 674), or placebo plus standard therapy (n = 675) intravenously over a 1-hour period on Days 0, 14, 28, and then every 28 days. In 2 of the trials (Trial 1 and Trial 3), treatment was given for 48 weeks, while in the other trial (Trial 2) treatment was given for 72 weeks [see Clinical Studies]. Because there was no apparent dose-related increase in the majority of adverse events observed with BENLYSTA, the safety data summarized below are presented for the 3 intravenous doses pooled, unless otherwise indicated; the adverse reaction table displays the results for the recommended intravenous dose of 10 mg/kg compared with placebo.

In these trials, 93% of patients treated with BENLYSTA plus standard therapy reported an adverse event compared with 92% treated with placebo plus standard therapy.

The most common serious adverse events were serious infections (6.0% and 5.2% in the groups receiving BENLYSTA and placebo plus standard therapy, respectively), some of which were fatal.

The most commonly reported adverse events, occurring in ≥5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis.

The proportion of patients who discontinued treatment due to any adverse reaction during the controlled clinical trials was 6.2% for patients receiving BENLYSTA plus standard therapy and 7.1% for patients receiving placebo plus standard therapy. The most common adverse reactions resulting in discontinuation of treatment (≥1% of patients receiving BENLYSTA or placebo) were infusion reactions (1.6% BENLYSTA and 0.9% placebo), lupus nephritis (0.7% BENLYSTA and 1.2% placebo), and infections (0.7% BENLYSTA and 1.0% placebo).

Table 1 lists adverse reactions, regardless of causality, occurring in at least 3% of patients with SLE who received BENLYSTA 10 mg/kg plus standard therapy and at an incidence at least 1% greater than that observed with placebo plus standard therapy in 3 controlled trials (Trials 1, 2, and 3).

Table 1: Incidence of Adverse Reactions Occurring in at Least 3% of Adult Patients with SLE Treated with BENLYSTA 10 mg/kg plus Standard Therapy and at Least 1% More Frequently than in Patients Receiving Placebo plus Standard Therapy

Adverse Reactions BENLYSTA 10 mg/kg + Standard Therapy
(n = 674) %
Placebo + Standard Therapy
(n = 675) %
Nausea 15 12
Diarrhea 12 9
Pyrexia 10 8
Nasopharyngitis 9 7
Bronchitis 9 5
Insomnia 7 5
Pain in extremity 6 4
Depression 5 4
Migraine 5 4
Pharyngitis 5 3
Cystitis 4 3
Leukopenia 4 2
Gastroenteritis viral 3 1

Infections

In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, the overall incidence of infections was 71% in patients receiving BENLYSTA compared with 67% in patients receiving placebo. The most frequent infections (>5% of patients receiving BENLYSTA) were upper respiratory tract infection, urinary tract infection, nasopharyngitis, sinusitis, bronchitis, and influenza. Infections leading to discontinuation of treatment occurred in 0.7% of patients receiving BENLYSTA and 1.0% of patients receiving placebo.

In a randomized, double-blind, placebo-controlled, 104-week trial of active lupus nephritis in adults receiving BENLYSTA administered intravenously (N = 448), the overall incidence of infections was 82% in patients receiving BENLYSTA compared with 76% in patients receiving placebo.

Serious Infections

In controlled trials of BENLYSTA administered intravenously in adults with SLE, the incidence of serious infections was 6.0% in patients receiving BENLYSTA and 5.2% in patients receiving placebo. The most frequent serious infections included pneumonia, urinary tract infections, cellulitis, and bronchitis. Fatal infections occurred in 0.3% (4/1,458) of patients receiving BENLYSTA and in 0.1% (1/675) of patients receiving placebo.

In a randomized, double-blind, placebo-controlled, 104-week trial of active lupus nephritis in adults receiving BENLYSTA administered intravenously, serious infections occurred in 14% of patients receiving BENLYSTA and in 17% of patients receiving placebo. Fatal infections occurred in 0.9% (2/224) of patients receiving BENLYSTA and in 0.9% (2/224) of patients receiving placebo.

In a randomized, double-blind, placebo-controlled, 52-week, postmarketing safety trial of BENLYSTA administered intravenously in adults with SLE (N = 4,003), the incidence of serious infections was 3.7% in patients receiving BENLYSTA compared with 4.1% in patients receiving placebo. Serious infections leading to discontinuation of treatment occurred in 1.0% of patients receiving BENLYSTA and in 0.9% of patients receiving placebo. Fatal infections occurred in 0.45% (9/2,002) of patients receiving BENLYSTA and in 0.15% (3/2,001) of patients receiving placebo, where the incidence of all-cause mortality was 0.50% (10/2,002) in patients receiving BENLYSTA and 0.40% (8/2,001) in patients receiving placebo.

Hypersensitivity Reactions, Including Anaphylaxis

In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, hypersensitivity reactions (occurring on the same day of infusion) were reported in 13% (191/1,458) of patients receiving BENLYSTA and 11% (76/675) of patients receiving placebo. Anaphylaxis was observed in 0.6% (9/1,458) of patients receiving BENLYSTA and 0.4% (3/675) of patients receiving placebo. Manifestations included hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea.

Infusion-Related Reactions

In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, adverse events associated with the infusion (occurring on the same day of the infusion) were reported in 17% (251/1,458) of patients receiving BENLYSTA and 15% (99/675) of patients receiving placebo. Serious infusion reactions (excluding hypersensitivity reactions) were reported in 0.5% of patients receiving BENLYSTA and 0.4% of patients receiving placebo and included bradycardia, myalgia, headache, rash, urticaria, and hypotension. The most common infusion reactions (≥3% of patients receiving BENLYSTA) were headache, nausea, and skin reactions.

Depression And Suicidality

In controlled clinical trials of BENLYSTA administered intravenously in adults with SLE (N = 2,133), psychiatric events were reported more frequently with BENLYSTA (16%) than with placebo (12%), primarily related to depression-related events (6.3% BENLYSTA; 4.7% placebo), insomnia (6.0% BENLYSTA; 5.3% placebo), and anxiety (3.9% BENLYSTA; 2.8% placebo). Serious psychiatric events were reported in 0.8% (12/1,458) of patients receiving BENLYSTA and 0.4% (3/675) of patients receiving placebo. Serious depression was reported in 0.4% (6/1,458) of patients receiving BENLYSTA and 0.1% (1/675) of patients receiving placebo. Two suicides (0.1%) were reported in patients receiving BENLYSTA (one with 10 mg/kg and one with 1 mg/kg).

In a randomized, double-blind, placebo-controlled, 52-week, postmarketing safety trial of BENLYSTA administered intravenously in adults with SLE (N = 4,003), serious psychiatric events were reported in 1.0% (20/2,002) of patients receiving BENLYSTA and 0.3% (6/2,001) of patients receiving placebo. Serious depression was reported in 0.3% (7/2,002) of patients receiving BENLYSTA and in <0.1% (1/2,001) receiving placebo. The overall incidence of serious suicidal ideation or behavior or self-injury without suicidal intent was 0.7% (15/2,002) of patients receiving BENLYSTA and 0.2% (5/2,001) of patients receiving placebo. On the Columbia-Suicide Severity Rating Scale (C-SSRS), 2.4% (48/1,974) of patients receiving BENLYSTA reported suicidal ideation or behavior compared with 2.0% (39/1,988) of patients receiving placebo. No suicide was reported in either group.

The intravenous trials above did not exclude patients with a history of psychiatric disorders.

Malignancy

In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, malignancies (including non-melanoma skin cancers) were reported in 0.4% of patients receiving BENLYSTA and 0.4% of patients receiving placebo. In the intravenous controlled clinical trials, malignancies, excluding non-melanoma skin cancers, were observed in 0.2% (3/1,458) and 0.3% (2/675) of patients receiving BENLYSTA and placebo, respectively.

Black/African-American Patients

The safety of BENLYSTA 10 mg/kg administered intravenously plus standard therapy (n = 331) compared with placebo plus standard therapy (n = 165) in Black patients with SLE (Trial 4) was consistent with the known safety profile of BENLYSTA administered intravenously plus standard therapy in the overall population [see Clinical Studies].

Adult Patients With Lupus Nephritis

The safety of BENLYSTA 10 mg/kg administered intravenously plus standard therapy (n = 224) compared with placebo plus standard therapy (n = 224) was evaluated in adults with active lupus nephritis for up to 104 weeks (Trial 5) [see Clinical Studies]. The adverse reactions observed were consistent with the known safety profile of BENLYSTA administered intravenously plus standard therapy in patients with SLE. Cases of myelosuppression, including febrile neutropenia, leukopenia, and pancytopenia, were observed in subjects who received induction therapy with cyclophosphamide followed by maintenance therapy with azathioprine, or mycophenolate.

Pediatric Patients

The safety of BENLYSTA administered intravenously plus standard therapy (n = 53) compared with placebo plus standard therapy (n = 40) was evaluated in 93 pediatric patients with SLE (Trial 6). The adverse reactions observed were consistent with those observed in adults with SLE [see Clinical Studies].

Clinical Trials With Subcutaneous Administration In Adults

The data described below reflect exposure to BENLYSTA administered subcutaneously plus standard therapy compared with placebo plus standard therapy in 836 patients with SLE in a controlled trial (Trial 7). In addition to standard therapy, patients received BENLYSTA 200 mg (n = 556) or placebo (n = 280) (2:1 randomization) once weekly for up to 52 weeks [see Clinical Studies].

In the trial, 81% of patients treated with BENLYSTA plus standard therapy reported an adverse event compared with 84% treated with placebo plus standard therapy. The proportion of patients who discontinued treatment due to any adverse reaction during the controlled clinical trial was 7.2% of patients receiving BENLYSTA plus standard therapy and 8.9% of patients receiving placebo plus standard therapy.

The safety profile observed for BENLYSTA administered subcutaneously plus standard therapy was consistent with the known safety profile of BENLYSTA administered intravenously plus standard therapy, with the exception of local injection site reactions.

Infections

In a controlled trial of BENLYSTA administered subcutaneously in adults with SLE (N = 836), the overall incidence of infections was 55% in patients receiving BENLYSTA compared with 57% in patients receiving placebo. The most commonly reported infections with BENLYSTA administered subcutaneously were similar to those reported with BENLYSTA administered intravenously.

Serious Infections

In a controlled trial of BENLYSTA administered subcutaneously in adults with SLE (N = 836), the incidence of serious infections was 4.1% in patients receiving BENLYSTA and 5.4% in patients receiving placebo. Fatal infections occurred in 0.5% (3/556) of patients receiving BENLYSTA and in none of the patients receiving placebo (0/280).

Depression And Suicidality

In a controlled trial of BENLYSTA administered subcutaneously in adults with SLE (N = 836), which excluded patients with a history of psychiatric disorders, psychiatric events were reported in 6% of patients receiving BENLYSTA and 11% of patients receiving placebo. Depression-related events were reported in 2.7% (15/556) of patients receiving BENLYSTA and 3.6% (10/280) of patients receiving placebo. Serious psychiatric events were reported in 0.2% (1/556) of patients receiving BENLYSTA and in no patients receiving placebo. There were no serious depression-related events or suicides reported in either group. On the C-SSRS, 1.3% (7/554) of patients receiving BENLYSTA reported suicidal ideation or behavior compared with 0.7% (2/277) of patients receiving placebo.

Malignancy

In a controlled clinical trial of BENLYSTA administered subcutaneously in adults with SLE (N = 836), the reports of malignancies were similar to those reported with BENLYSTA administered intravenously.

Injection Site Reactions

In a controlled clinical trial of BENLYSTA administered subcutaneously in adults with SLE (N = 836), the frequency of injection site reactions was 6.1% (34/556) for patients receiving BENLYSTA plus standard therapy and 2.5% (7/280) for patients receiving placebo plus standard therapy. These injection site reactions (most commonly pain, erythema, hematoma, pruritus, and induration) were mild to moderate in severity. The majority (94%) did not necessitate discontinuation of treatment.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to belimumab with the incidence of antibodies in other studies or to other products may be misleading.

In Trials 2 and 3 (intravenous dosing in adults with SLE), anti-belimumab antibodies were detected in 4 of 563 (0.7%) patients receiving BENLYSTA 10 mg/kg and in 27 of 559 (4.8%) patients receiving BENLYSTA 1 mg/kg. The reported frequency for the group receiving 10 mg/kg may underestimate the actual frequency due to lower assay sensitivity in the presence of high drug concentrations. Neutralizing antibodies were detected in 3 patients receiving BENLYSTA 1 mg/kg. Three patients with anti-belimumab antibodies experienced mild infusion reactions of nausea, erythematous rash, pruritus, eyelid edema, headache, and dyspnea; none of the reactions was life-threatening. In Trial 4 (intravenous dosing in adult Black patients), anti­belimumab antibodies were detected in 2 of 321 (0.6%) patients receiving BENLYSTA 10 mg/kg during the 52-week, placebo-controlled period. In Trial 5 (intravenous dosing in adults with lupus nephritis), there was no formation of anti-belimumab antibodies in 224 patients receiving BENLYSTA 10 mg/kg plus standard therapy during the 104-week, placebo-controlled period. In Trial 6 (intravenous dosing in pediatric patients with SLE), there was no formation of anti-belimumab antibodies in 53 patients receiving BENLYSTA 10 mg/kg plus standard therapy during the 52-week, placebo-controlled period. In Trial 7 (subcutaneous dosing in adults with SLE), there was no formation of anti-belimumab antibodies in 556 patients receiving BENLYSTA 200 mg during the 52-week, placebo-controlled period.

The clinical relevance of the presence of anti-belimumab antibodies is not known.

The data reflect the percentage of patients whose test results were positive for antibodies to belimumab in specific assays.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of BENLYSTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Fatal anaphylaxis [see WARNINGS AND PRECAUTIONS].

DRUG INTERACTIONS

Formal drug interaction studies have not been performed with BENLYSTA. In clinical trials, BENLYSTA was administered concomitantly with other drugs, including corticosteroids, antimalarials, immunomodulatory and immunosuppressive agents (including azathioprine, cyclophosphamide, methotrexate, and mycophenolate), angiotensin pathway antihypertensives, HMG-CoA reductase inhibitors (statins), and/or non-steroidal anti-inflammatory drugs (NSAIDs) without evidence of a clinically meaningful effect of these concomitant medications on belimumab pharmacokinetics. The effect of belimumab on the pharmacokinetics of other drugs has not been evaluated [see CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Benlysta (Belimumab)

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© Benlysta Patient Information is supplied by Cerner Multum, Inc. and Benlysta Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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