Benlysta
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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of new 
safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 
4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Benlysta 200 mg solution for injection in pre-filled pen. 
Benlysta 200 mg solution for injection in pre-filled syringe. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Pre-filled pen 
Each 1-ml pre-filled pen contains 200 mg of belimumab. 
 
Pre-filled syringe 
Each 1-ml pre-filled syringe contains 200 mg of belimumab. 
 
Belimumab is a human, IgG1λ monoclonal antibody, produced in a mammalian cell line (NS0) by 
recombinant DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in pre-filled pen (injection) 
Solution for injection in pre-filled syringe (injection) 
 
A clear to opalescent, colourless to pale yellow solution, with a pH of 6. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Benlysta is indicated as add-on therapy in adult patients with active, autoantibody-positive systemic lupus 
erythematosus (SLE) with a high degree of disease activity (e.g., positive anti-dsDNA and low complement) 
despite standard therapy (see section 5.1). 
 
4.2 Posology and method of administration 
 
Benlysta treatment should be initiated and supervised by a qualified physician experienced in the diagnosis 
and treatment of SLE. It is recommended that the first subcutaneous injection of Benlysta should be under 
the supervision of a healthcare professional in a setting that is sufficiently qualified to manage 
hypersensitivity reactions, if necessary. The healthcare professional must provide proper training in 
subcutaneous technique and education about signs and symptoms of hypersensitivity reactions (see section 
4.4). A patient may self-inject or the patient caregiver may administer Benlysta after the healthcare 
professional determines that it is appropriate. 
 
Posology 
 
The recommended dose is 200 mg once weekly, administered subcutaneously. Dosing is not based on weight 
(see section 5.2). 
 



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The patient’s condition should be evaluated continuously. Discontinuation of treatment with Benlysta should 
be considered if there is no improvement in disease control after 6 months of treatment. 
 
If a dose is missed, it should be administered as soon as possible. Thereafter, patients 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 necessary to administer two doses on the same day. 
 
If patients wish to change their weekly dosing day, a new dose can be given on the newly preferred day of 
the week.  Thereafter the patient should continue with the new weekly schedule from that day, even if the 
dosing interval may be temporarily less than a week.  
 
Transition from intravenous to subcutaneous administration 
 
If a patient is being transitioned from Benlysta intravenous administration to subcutaneous administration, 
the first subcutaneous injection should be administered 1 to 4 weeks after the last intravenous dose (see 
section 5.2). 
 
Special populations 
 
Elderly 
Data on patients ≥65 years are limited (see section 5.1). Benlysta should be used with caution in the elderly. 
Dose adjustment is not required (see section 5.2). 
 
Renal impairment 
Belimumab has been studied in a limited number of SLE patients with renal impairment. On the basis of the 
available information, dose adjustment is not required in patients with mild, moderate or severe renal 
impairment. Caution is however recommended in patients with severe renal impairment due to the lack of 
data (see section 5.2). 
 
Hepatic impairment 
No specific studies with Benlysta have been conducted in patients with hepatic impairment. Patients with 
hepatic impairment are unlikely to require dose adjustment (see section 5.2). 
 
Paediatric population 
The safety and efficacy of Benlysta subcutaneous administration in children and adolescents (< 18 years of 
age) has not been established. No data are available. 
 
Method of administration 
 
The pre-filled pen or pre-filled syringe should be used for subcutaneous injection only. The recommended 
injection sites are the abdomen or thigh. When injecting in the same region, patients should be advised to use 
a different injection site each week; injections should never be given into areas where the skin is tender, 
bruised, red, or hard. 
 
Comprehensive instructions for subcutaneous administration of Benlysta in a pre-filled pen or pre-filled 
syringe are provided at the end of the package leaflet (see Step-by-step instructions). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve traceability of biological medicinal products, the tradename and the batch number of the 
administered product should be clearly recorded. 



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Benlysta has not been studied in the following patient groups and is not recommended in: 
 

• severe active central nervous system lupus 
 

• severe active lupus nephritis (see section 5.1) 
 

• HIV 
 

• a history of, or current, hepatitis B or C 
 

• hypogammaglobulinaemia (IgG <400 mg/dl) or IgA deficiency (IgA <10 mg/dl) 
 
•  a history of major organ transplant or hematopoietic stem cell/marrow transplant or renal 

transplant. 
 
Concomitant use with B cell targeted therapy or cyclophosphamide 
 
Benlysta has not been studied in combination with other B cell targeted therapy or intravenous 
cyclophosphamide. Caution should be exercised if Benlysta is co-administered with other B cell targeted 
therapy or cyclophosphamide. 
 
Hypersensitivity  
 
Administration of subcutaneous or intravenous Benlysta may result in hypersensitivity reactions which can 
be severe, and fatal. In the event of a severe reaction, Benlysta administration must be interrupted and 
appropriate medical therapy administered (see section 4.2). The risk of hypersensitivity reactions is greatest 
with the first two doses; however the risk should be considered for every administration. Patients with a 
history of multiple drug allergies or significant hypersensitivity may be at increased risk. Recurrence of 
clinically significant reactions after initial appropriate treatment of symptoms has also been observed (see 
sections 4.2 and 4.8). 
 
Patients should be advised that hypersensitivity reactions are possible, on the day of, or several days after 
administration, and be informed of potential signs and symptoms and the possibility of recurrence. Patients 
should be instructed to seek immediate medical attention if they experience any of these symptoms. The 
package leaflet should be available to the patient. Delayed-type, non-acute hypersensitivity reactions have 
also been observed and included symptoms such as rash, nausea, fatigue, myalgia, headache, and facial 
oedema. 
 
In intravenous clinical studies, serious infusion and hypersensitivity reactions included anaphylactic reaction, 
bradycardia, hypotension, angioedema, and dyspnoea. Please refer to the Summary of Product 
Characteristics for Benlysta powder for concentrate for solution for infusion (section 4.4). 
 
Infections 
 
The mechanism of action of belimumab could increase the risk for the development of infections, including 
opportunistic infections. In controlled clinical studies, the incidence of serious infections was similar across 
the Benlysta and placebo groups; however, fatal infections (e.g. pneumonia and sepsis) occurred more 
frequently in patients receiving Benlysta compared with placebo (see section 4.8). Pneumococcal vaccination 
should be considered before initiating Benlysta treatment. Benlysta should not be initiated in patients with 
active serious infections (including serious chronic infections). Physicians should exercise caution and 
carefully assess if the benefits are expected to outweigh the risks when considering the use of Benlysta in 
patients with a history of recurrent infection. Physicians should advise patients to contact their health care 
provider if they develop symptoms of an infection. Patients who develop an infection while undergoing 
treatment with Benlysta should be monitored closely and careful consideration given to interrupting 
immunosuppressant therapy including Benlysta until the infection is resolved. The risk of using Benlysta in 
patients with active or latent tuberculosis is unknown. 



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Depression and suicidality 
 
In controlled clinical intravenous and subcutaneous studies, psychiatric disorders (depression, suicidal 
ideation and behaviour including suicides) have been reported more frequently in patients receiving Benlysta 
(see section 4.8). Physicians should assess the risk of depression and suicide considering the patient’s 
medical history and current psychiatric status before treatment with Benlysta and continue to monitor 
patients during treatment. Physicians should advise patients (and caregivers where appropriate) to contact 
their health care provider about new or worsening psychiatric symptoms. In patients who experience such 
symptoms, treatment discontinuation should be considered. 
 
Progressive multifocal leukoencephalopathy 
 
Progressive multifocal leukoencephalopathy (PML) has been reported with Benlysta treatment for SLE. 
Physicians should be particularly alert to symptoms suggestive of PML that patients may not notice (e.g., 
cognitive, neurological or psychiatric symptoms or signs). Patients should be monitored for any of these new 
or worsening symptoms or signs, and if such symptoms/signs occur, referral to a neurologist and appropriate 
diagnostic measures for PML should be considered. If PML is suspected, further dosing must be suspended 
until PML has been excluded. 
 
Immunisation 
 
Live vaccines should not be given for 30 days before, or concurrently with Benlysta, as clinical safety has 
not been established. No data are available on the secondary transmission of infection from persons receiving 
live vaccines to patients receiving Benlysta. 
 
Because of its mechanism of action, belimumab may interfere with the response to immunisations. However, 
in a small study evaluating the response to a 23-valent pneumococcal vaccine, overall immune responses to 
the different serotypes were similar in SLE patients receiving Benlysta compared with those receiving 
standard immunosuppressive treatment at the time of vaccination. There are insufficient data to draw 
conclusions regarding response to other vaccines. 
 
Limited data suggest that Benlysta does not significantly affect the ability to maintain a protective immune 
response to immunisations received prior to administration of Benlysta. In a substudy, a small group of 
patients who had previously received either tetanus, pneumococcal or influenza vaccinations were found to 
maintain protective titres after treatment with Benlysta. 
 
Malignancies and lymphoproliferative disorders 
 
Immunomodulatory medicinal products, including Benlysta, may increase the risk of malignancy. Caution 
should be exercised when considering Benlysta therapy for patients with a history of malignancy or when 
considering continuing treatment in patients who develop malignancy. Patients with malignant neoplasm 
within the last 5 years have not been studied, with the exception of those with basal or squamous cell cancers 
of the skin, or cancer of the uterine cervix, that has been fully excised or adequately treated. 
 
Sodium content 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No in vivo interaction studies have been performed. The formation of some CYP450 enzymes is suppressed 
by increased levels of certain cytokines during chronic inflammation. It is not known if belimumab could be 
an indirect modulator of such cytokines. A risk for indirect reduction of CYP activity by belimumab cannot 
be excluded. On initiation or discontinuation of belimumab, therapeutic monitoring should be considered for 
patients being treated with CYP substrates with a narrow therapeutic index, where the dose is individually 
adjusted (e.g. warfarin). 



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4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/Contraception in males and females 
 
Women of childbearing potential must use effective contraception during Benlysta treatment and for at least 
4 months after the last treatment. 
 
Pregnancy 
 
There are a limited amount of data from the use of Benlysta in pregnant women. No formal studies have 
been conducted. Besides an expected pharmacological effect i.e. reduction of B cells, animal studies in 
monkeys do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 
5.3).  
Benlysta should not be used during pregnancy unless the potential benefit justifies the potential risk to the 
foetus.  
 
Breast-feeding 
 
It is unknown whether Benlysta is excreted in human milk or is absorbed systemically after ingestion. 
However, belimumab was detected in the milk from female monkeys administered 150 mg/kg every 2 
weeks. 
 
Because maternal antibodies (IgG) are excreted in breast milk, it is recommended that a decision should be 
made whether to discontinue breast-feeding or to discontinue Benlysta therapy, taking into account the 
benefit of breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
There are no data on the effects of belimumab on human fertility. Effects on male and female fertility have 
not been formally evaluated in animal studies (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. No detrimental 
effects on such activities are predicted from the pharmacology of belimumab. The clinical status of the 
subject and the adverse reaction profile of Benlysta should be borne in mind when considering the patient's 
ability to perform tasks that require judgement, motor or cognitive skills. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety of belimumab in patients with SLE has been evaluated in 3 pre-registration, placebo-controlled 
intravenous studies, 1 placebo-controlled subcutaneous study, and one post-marketing, placebo-controlled 
intravenous study. 
 
The data presented in the table below reflect exposure to Benlysta administered (10 mg/kg intravenously 
over a 1-hour period on Days 0, 14, 28, and then every 28 days for up to 52 weeks) in 674 patients with SLE, 
including 472 exposed for at least 52 weeks, and 556 patients exposed to 200 mg Benlysta subcutaneously 
once weekly for up to 52 weeks. The safety data presented include data beyond Week 52 in some patients. 
Data from post-marketing reports are also included. 
 
The majority of patients were also receiving one or more of the following concomitant treatments for SLE: 
corticosteroids, immunomodulatory medicinal products, anti-malarials, non-steroidal anti-inflammatory 
medicinal products. 
 



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Adverse reactions were reported in 87% of Benlysta-treated patients and 90% of placebo-treated patients. 
The most frequently reported adverse reactions (≥5% of patients with SLE treated with Benlysta plus 
standard of care and at a rate ≥1% greater than placebo) were viral upper respiratory tract infections, 
bronchitis, and diarrhoea. The proportion of patients who discontinued treatment due to adverse reactions 
was 7% for Benlysta-treated patients and 8% for placebo-treated patients. 
 
Tabulated list of adverse reactions 
 
Adverse reactions are listed below by MedDRA system organ class and by frequency. The frequency 
categories used are: 
 
Very common  ≥1/10 
Common  ≥1/100 to <1/10 
Uncommon  ≥1/1,000 to <1/100 
Rare    ≥1/10,000 to <1/1000 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The 
frequency given is the highest seen with either formulation. 
 

System organ class Frequency 
 

Adverse reaction(s) 

Infections and infestations1 Very common Bacterial infections, e.g. bronchitis, 
urinary tract infection 
 

Common Gastroenteritis viral, pharyngitis, 
nasopharyngitis, viral upper 
respiratory tract infection 
 

Blood and lymphatic system 
disorders 
 

Common Leucopenia 

Immune system disorders 
 

Common 
 

Hypersensitivity reactions2 

Uncommon Anaphylactic reaction 
 

Rare Delayed-type, non-acute 
hypersensitivity reactions 
 

Psychiatric disorders 
 

Common 
 

Depression 

Uncommon 
 

Suicidal behaviour, suicidal ideation 
 

Nervous system disorders 
 

Common Migraine 

Gastrointestinal disorders Very common Diarrhoea, nausea 
 

Skin and subcutaneous tissue 
disorders 

Common Injection site reactions3 
 

Uncommon Angioedema, urticaria, rash 
 

Musculoskeletal and 
connective tissue disorders 
 

Common Pain in extremity 

General disorders and 
administration site conditions 
 

Common Infusion or injection-related systemic 
reactions2, pyrexia 
 



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1 See ‘Description of selected adverse reactions’ and section 4.4 ‘Infections’ for further information. 
2 ‘Hypersensitivity reactions’ covers a group of terms, including anaphylaxis, and can manifest as a range of 
symptoms including hypotension, angioedema, urticaria or other rash, pruritus, and dyspnoea. ‘Infusion or 
injection-related systemic reactions’ covers a group of terms and can manifest as a range of symptoms 
including bradycardia, myalgia, headache, rash, urticaria, pyrexia, hypotension, hypertension, dizziness, and 
arthralgia. Due to overlap in signs and symptoms, it is not possible to distinguish between hypersensitivity 
reactions and infusion reactions in all cases. 
3 Applies to subcutaneous formulation only. 
 
Description of selected adverse reactions 
 
Data presented below are pooled from the intravenous clinical studies (10 mg/kg intravenous dose only) and 
the subcutaneous clinical study. ‘Infections’ and ‘Psychiatric disorders’ also include data from a 
post-marketing study. 
 
Infusion or injection-related systemic reactions and hypersensitivity: Infusion or injection-related systemic 
reactions and hypersensitivity were generally observed on the day of administration, but acute 
hypersensitivity reactions may also occur several days after dosing. Patients with a history of multiple drug 
allergies or significant hypersensitivity reactions may be at increased risk. 
 
The incidence of infusion reactions and hypersensitivity reactions after intravenous administration occurring 
within 3 days of an infusion was 12% in the group receiving Benlysta and 10% in the group receiving 
placebo, with 1.2% and 0.3%, respectively, requiring permanent treatment discontinuation. 
 
The incidence of post-injection systemic reactions and hypersensitivity reactions occurring within 3 days of 
subcutaneous administration was 7% in the group receiving Benlysta and 9% in the group receiving placebo. 
Clinically significant hypersensitivity reactions associated with Benlysta administered subcutaneously and 
requiring permanent treatment discontinuation were reported in 0.2% of patients receiving Benlysta and in 
no patients receiving placebo. 
 
Infections: The overall incidence of infections in intravenous and subcutaneous pre-registration studies was 
63% in both groups receiving Benlysta or placebo. Infections occurring in at least 3% of patients receiving 
Benlysta and at least 1% more frequently than patients receiving placebo were viral upper respiratory tract 
infection, bronchitis, and urinary tract infection bacterial. Serious infections occurred in 5% of patients in 
both groups receiving Benlysta or placebo; serious opportunistic infections accounted for 0.4% and 0% of 
these, respectively. Infections leading to discontinuation of treatment occurred in 0.7% of patients receiving 
Benlysta and 1.5% of patients receiving placebo. Some infections were severe or fatal. 
 
In a randomised, double-blind, 52-week, post-marketing safety study (BEL115467) which assessed mortality 
and specific adverse events in adults, serious infections occurred in 3.7% of patients receiving Benlysta 
(10 mg/kg intravenously) vs 4.1% of patients receiving placebo. However, fatal infections (e.g. pneumonia 
and sepsis) occurred in 0.45% (9/2002) of Benlysta-treated patients vs 0.15% (3/2001) of patients receiving 
placebo, while the incidence of all-cause mortality was 0.50% (10/2002) vs 0.40% (8/2001), respectively. 
Most fatal infections were observed during the first 20 weeks of treatment with Benlysta. 
 
Psychiatric disorders: In the pre-registration intravenous clinical studies, serious psychiatric events were 
reported in 1.2% (8/674) of patients receiving Benlysta 10 mg/kg and 0.4% (3/675) of patients receiving 
placebo. Serious depression was reported in 0.6% (4/674) of patients receiving Benlysta 10 mg/kg and 0.3% 
(2/675) of patients receiving placebo. There were two suicides in Benlysta-treated patients (including one 
receiving 1 mg/kg Benlysta). 
 
In a post-marketing study, serious psychiatric events were reported in 1.0% (20/2002) of patients receiving 
Benlysta and 0.3% (6/2001) of patients receiving placebo. Serious depression was reported in 0.3% (7/2002) 
of patients receiving Benlysta and <0.1% (1/2001) of patients receiving placebo. The overall incidence of 
serious suicidal ideation or behaviour or self-injury without suicidal intent was 0.7% (15/2002) in patients 
receiving Benlysta and 0.2% (5/2001) in the placebo group. No suicide was reported in either group. 
 



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The intravenous studies did not exclude patients with a history of psychiatric disorders. 
 
In the subcutaneous clinical study, which excluded patients with a history of psychiatric disorders, 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. 
 
Leucopenia: The incidence of leucopenia reported as an adverse event was 3% in the group receiving 
Benlysta and 2% in the group receiving placebo. 
 
Injection site reactions: In the subcutaneous study, the frequency of injection site reactions was 6.1% 
(34/556) and 2.5% (7/280) for patients receiving Benlysta and placebo, respectively. These injection site 
reactions (most commonly pain, erythema, hematoma, pruritus and induration) were mild to moderate in 
severity. The majority did not necessitate drug discontinuation. 
 
Reporting of suspected adverse reactions 
  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 
to report any suspected adverse reactions via the national reporting system listed in Appendix V. 
 
4.9 Overdose 
 
There is limited clinical experience with overdose of Benlysta. Adverse reactions reported in association with 
cases of overdose have been consistent with those expected for belimumab. 
 
Two doses up to 20 mg/kg administered 21 days apart by intravenous infusion have been given to humans 
with no increase in incidence or severity of adverse reactions compared with doses of 1, 4, or 10 mg/kg. 
 
In the case of inadvertent overdose, patients should be carefully observed and supportive care administered, 
as appropriate. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Selective immunosuppressants, ATC code: L04AA26 
 
Mechanism of action 
 
Belimumab is a human IgG1λ monoclonal antibody specific for soluble human B Lymphocyte Stimulator 
protein (BLyS, also referred to as BAFF and TNFSF13B). Belimumab blocks the binding of soluble BLyS, a 
B cell survival factor, to its receptors on B cells. Belimumab does not bind B cells directly, but by binding 
BLyS, belimumab inhibits the survival of B cells, including autoreactive B cells, and reduces the 
differentiation of B cells into immunoglobulin-producing plasma cells.  
 
BLyS levels are elevated in patients with SLE and other autoimmune diseases. There is an association 
between plasma BLyS levels and SLE disease activity. The relative contribution of BLyS levels to the 
pathophysiology of SLE is not fully understood. 
 
Pharmacodynamic effects 
 
Median IgG levels at Week 52 were reduced by 11% in patients receiving Benlysta compared with an 
increase of 0.7% in patients receiving placebo. 
 
In patients with anti-dsDNA antibodies at baseline, median anti-dsDNA antibodies levels at Week 52 were 
reduced by 56% in patients receiving Benlysta compared with 41% in patients receiving placebo. In patients 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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with anti-dsDNA antibodies at baseline, by Week 52, 18% of patients treated with Benlysta had converted to 
anti-dsDNA negative compared with 15% of the patients receiving placebo. 
 
In patients with low complement levels, normalization of C3 and C4 was observed by Week 52 in 42% and 
53% of patients receiving Benlysta and in 21% and 20% of patients receiving placebo, respectively.  
 
Benlysta significantly reduced circulating overall, transitional, naïve, and SLE B cells, as well as plasma 
cells at Week 52. Reductions in naïve and transitional B cells, as well as the SLE B cell subset were 
observed as early as Week 8. Memory cells increased initially and slowly declined toward baseline levels by 
Week 52. 
 
The B cell and IgG response to long term treatment with intravenous Benlysta was assessed in an 
uncontrolled extension study. After 7 and a half years of treatment (including the 72-week parent study), a 
substantial and sustained decrease in various B cell subsets was observed leading to 87% median reduction 
in naïve B cells, 67% in memory B cells, 99% in activated B cells, and 92% median reduction in plasma cells 
after more than 7 years of treatment. After about 7 years, a 28% median reduction in IgG levels was 
observed, with 1.6% of subjects experiencing a decrease in IgG levels to below 400 mg/dl. Over the course 
of the study, the reported incidence of AEs generally remained stable or declined.  
 
Immunogenicity 
 
In the subcutaneous study where serum samples from more than 550 patients with SLE were tested, no 
anti-belimumab antibodies were detected during or after treatment with belimumab 200 mg subcutaneously. 
 
Clinical efficacy and safety 
 
Subcutaneous injection 
The efficacy of Benlysta administered subcutaneously was evaluated in a randomised, double-blind, 
placebo-controlled 52-week Phase III study (HGS1006-C1115; BEL112341) in 836 adult patients with a 
clinical diagnosis of SLE according to the American College of Rheumatology classification criteria. 
Eligible patients had active SLE disease, defined as a SELENA-SLEDAI score ≥8 and positive anti-nuclear 
antibody (ANA or anti-dsDNA) test results (ANA titre ≥1:80 and/or a positive anti-dsDNA [≥30 units/ml]) 
at screening. Patients were on a stable SLE treatment regimen (standard of care) consisting of any of the 
following (alone or in combination): corticosteroids, anti-malarials, NSAIDs or other immunosuppressives. 
Patients were excluded from the study if they had severe active central nervous system lupus or severe active 
lupus nephritis. 
 
This study was conducted in the US, South America, Europe and Asia. Patient median age was 37 years 
(range: 18 to 77 years), and the majority (94%) were female. Background medicinal products included 
corticosteroids (86%; >7.5 mg/day prednisone equivalent 60%), immunosuppressives (46%), and 
anti-malarials (69%). Patients were randomised in a 2:1 ratio to receive belimumab 200 mg or placebo 
subcutaneously once weekly for 52 weeks. 
 
At baseline 62.2% of patients had high disease activity (SELENA SLEDAI score ≥10), 88% of patients had 
mucocutaneous, 78% had musculoskeletal, 8% had haematological, 12% had renal, and 8% had vascular 
organ involvement. 
 
The primary efficacy endpoint was a composite endpoint (SLE Responder Index) 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 score (PGA) 

 
The SLE Responder Index measures improvement in SLE disease activity, without worsening in any organ 
system, or in the patient’s overall condition. 



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Table 1: Response rate at week 52 

Response Placebo 
 

(n=279) 
 

Benlysta 
200 mg weekly 

(n=554)  

SLE responder index 
 
 
Observed difference vs 
placebo 
 
Odds ratio (95% CI) vs 
placebo 

48.4% 

 

 

61.4% 
(p=0.0006) 

 
12.98% 

 
 

1.68 
(1.25, 2.25) 

 
Components of SLE responder index 
 
Percent of patients with 
reduction in SELENA- 
SLEDAI ≥4 
 

49.1% 

 

62.3% 
(p=0.0005) 

Percent of patients with no 
worsening by BILAG index 

74.2% 80.9% 
(p=0.0305) 

 
Percent of patients with no 
worsening by PGA  

72.8% 81.2% 
(p=0.0061) 

 
All patients received standard therapy. 
 
The differences between the treatment groups were apparent by Week 16 and sustained through Week 52 
(Figure 1). 

 

Figure 1. Proportion of SRI responders by visit 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Flares in SLE were defined by the modified SELENA SLEDAI SLE Flare Index. The risk of first flare was 
reduced by 22% during the 52 weeks of observation in the group receiving Benlysta compared with the 
group receiving placebo (hazard ratio=0.78; p=0.0061). The median time to the first flare among patients 
having a flare was delayed in patients receiving Benlysta compared with placebo (190 days vs. 141 days).  

Belimumab + Standard Therapy (n = 554) 
Placebo + Standard Therapy (n = 279) 
* P<0.05 

R
es

po
nd

er
s (

%
) 

Time (weeks) 



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Severe flares were observed in 10.6% of patients in the group receiving Benlysta compared with 18.2% of 
patients in the group receiving placebo over the 52 weeks of observation (observed treatment difference 
= -7.6%). The risk of severe flares was reduced by 49% during the 52 weeks of observation in the group 
receiving Benlysta compared with the group receiving placebo (hazard ratio=0.51; p=0.0004). The median 
time to the first severe flare among patients having a severe flare was delayed in patients receiving Benlysta 
compared with placebo (171 days vs. 118 days). 
 
The percentage of patients receiving greater than 7.5 mg/day prednisone (or equivalent) at baseline whose 
average corticosteroid dose was reduced by at least 25% from baseline to a dose equivalent to prednisone 
≤7.5 mg/day during Weeks 40 through 52, was 18.2% in the group receiving Benlysta and 11.9% in the 
group receiving placebo (p=0.0732). 
 
Benlysta demonstrated improvement in fatigue compared with placebo measured by the FACIT-Fatigue 
Scale. The adjusted mean change of score at Week 52 from baseline is significantly greater with Benlysta 
compared to placebo (4.4 vs. 2.7, p=0.0130). 
 
Subgroup analysis of the primary endpoint demonstrated that the greatest benefit was observed in patients 
with higher disease activity at baseline including patients with SELENA SLEDAI scores ≥ 10 or patients 
requiring steroids to control their disease or patients with low complement levels. 
 
An additional, previously identified serologically active group, those patients with low complement and 
positive anti-dsDNA at baseline, also demonstrated a greater relative response, see Table 2 for results of this 
example of a higher disease activity group. 
 



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Table 2: Patients with low complement and positive anti-dsDNA at baseline 
 

Subgroup  Anti-dsDNA positive AND low complement 
 

 Placebo Benlysta 
200 mg weekly 

 
 
SRI response rate at week 52 (%) 
 
Observed treatment difference vs. placebo (%) 

(n=108) 
 

47.2 

(n=246) 
 

64.6 (p=0.0014) 
 

17.41 
 

Severe flares over 52 weeks: 
 
Patients experiencing a severe flare (%) 
 
Observed treatment difference vs. placebo (%) 
 
Time to severe flare [Hazard ratio (95% CI)] 

(n=108) 
 

31.5 
 

(n=248) 
  

14.1 
  

17.4 
 

0.38 (0.24, 0.61) 
(p<0.0001) 

 
 
Prednisone reduction by ≥25% from baseline to 
≤7.5 mg/day during weeks 24 through 52* (%) 
 
Observed treatment difference vs. placebo (%) 

(n=70) 
 

11.4 

(n=164) 
 

20.7 (p=0.0844) 
 

  
9.3 

 

FACIT-fatigue score improvement from baseline at 
week-52 (mean): 

Observed treatment difference vs. placebo (median 
difference) 

(n=108) 
 

2.4 

(n=248) 
 

4.6 (p=0.0324) 
 

2.1 

* Among patients with baseline prednisone dose >7.5 mg/day 
 
Age and race 
 
There were no observed differences in efficacy or safety in patients ≥65 years who received Benlysta 
intravenously or subcutaneously compared to the overall population in placebo-controlled studies; however, 
the number of patients aged ≥65 years (62 patients for efficacy and 219 for safety) is not sufficient to 
determine whether they respond differently to younger patients. 
 
There were too few black patients enrolled in the placebo-controlled studies with subcutaneous Benlysta to 
draw meaningful conclusions about the effects of race on clinical outcomes. 
 
The safety and efficacy of Benlysta administered intravenously have been studied in black patients. The 
currently available data are described in the Summary of Product Characteristics of Benlysta 120 mg and 
400 mg powder for concentrate for solution for infusion. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with Benlysta 
subcutaneous administration in one or more subsets of the paediatric population in SLE (see section 4.2 for 
information on paediatric use). 
 



14 

5.2 Pharmacokinetic properties 
 
The subcutaneous pharmacokinetic parameters below are based on population parameter estimates from 
661 subjects, comprised of 554 SLE patients and 107 healthy subjects, who received Benlysta 
subcutaneously. 
 
Absorption 
 
Benlysta in pre-filled pen or pre-filled syringe is administered by subcutaneous injection. 
 
Following subcutaneous administration the bioavailability of belimumab was approximately 74%. Steady-
state exposure was reached after approximately 11 weeks of subcutaneous administration. The maximum 
serum concentration (Cmax) of belimumab at steady state was 108 µg/ml.   
 
Distribution 
 
Belimumab was distributed to tissues with steady-state volume (Vss) of distribution of approximately 
5 litres. 
 
Biotransformation 
 
Belimumab is a protein for which the expected metabolic pathway is degradation to small peptides and 
individual amino acids by widely distributed proteolytic enzymes. Classical biotransformation studies have 
not been conducted. 
 
Elimination 
 
Following subcutaneous administration, belimumab had a terminal half-life of 18.3 days. The systemic 
clearance was 204 ml/day. 
 
Special Patient Populations 
 
Paediatric population: No pharmacokinetic data are available for subcutaneous administration of Benlysta in 
paediatric patients. 
 
Elderly: Benlysta has been studied in a limited number of elderly patients. Age did not affect belimumab 
exposure in the subcutaneous population pharmacokinetic analysis. However, given the small number of 
subjects ≥65, an effect of age cannot be ruled out conclusively. 
 
Renal impairment: No specific studies have been conducted to examine the effects of renal impairment on 
the pharmacokinetics of belimumab. During clinical development, Benlysta was studied in a limited number 
of SLE patients with mild (creatinine clearance [CrCl] ≥60 and <90 ml/min), moderate (CrCl ≥30 and 
<60 ml/min), or severe (CrCl ≥15 and <30 ml/min) renal impairment: 121 patients with mild renal 
impairment and 30 patients with moderate renal impairment received Benlysta subcutaneously; 770 patients 
with mild renal impairment, 261 patients with moderate renal impairment and 14 patients with severe renal 
impairment received Benlysta intravenously. 
 
No clinically significant reduction in systemic clearance as a result of renal impairment was observed. 
Therefore, no dose adjustment is recommended for patients with renal impairment. 
 
Hepatic impairment: No specific studies have been conducted to examine the effects of hepatic impairment 
on the pharmacokinetics of belimumab. IgG1 molecules such as belimumab are catabolised by widely 
distributed proteolytic enzymes, which are not restricted to hepatic tissue and changes in hepatic function are 
unlikely to have any effect on the elimination of belimumab. 
 



15 

Body weight/Body mass index (BMI) 
 
The effects of body weight and BMI on belimumab exposure after subcutaneous administration were not 
considered clinically meaningful. There was no significant impact on efficacy and safety based on weight. 
Therefore, no dose adjustment is recommended. 
 
Transitioning from intravenous to subcutaneous administration 
 
SLE patients transitioning from 10 mg/kg intravenously every 4 weeks to 200 mg subcutaneously weekly 
using a 1 to 4 week switching interval had pre-dose belimumab serum concentrations at their first 
subcutaneous dose close to their eventual subcutaneous steady-state trough concentration (see section 4.2).  
 
Based on simulations with population PK parameters the steady-state average belimumab concentrations for 
200 mg subcutaneous every week were similar to 10 mg/kg intravenous every 4 weeks. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on studies of repeated dose toxicity and toxicity 
to reproduction. 
 
Intravenous and subcutaneous administration to monkeys resulted in the expected reduction in the number of 
peripheral and lymphoid tissue B cell counts with no associated toxicological findings. 
 
Reproductive studies have been performed in pregnant cynomolgus monkeys receiving belimumab 
150 mg/kg by intravenous infusion (approximately 9 times the anticipated maximum human clinical 
exposure) every 2 weeks for up to 21 weeks, and belimumab treatment was not associated with direct or 
indirect harmful effects with respect to maternal toxicity, developmental toxicity, or teratogenicity.  
 
Treatment-related findings were limited to the expected reversible reduction of B cells in both dams and 
infants and reversible reduction of IgM in infant monkeys. B cell numbers recovered after the cessation of 
belimumab treatment by about 1 year post-partum in adult monkeys and by 3 months of life in infant 
monkeys; IgM levels in infants exposed to belimumab in utero recovered by 6 months of age. 
 
Effects on male and female fertility in monkeys were assessed in the 6-month repeat dose toxicology studies 
of belimumab at doses up to and including 50 mg/kg. No treatment-related changes were noted in the male 
and female reproductive organs of sexually mature animals. An informal assessment of menstrual cycling in 
females demonstrated no belimumab-related changes. 
 
As belimumab is a monoclonal antibody no genotoxicity studies have been conducted. No carcinogenicity 
studies or fertility studies (male or female) have been performed. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Arginine hydrochloride 
Histidine 
Histidine monohydrochloride 
Polysorbate 80 
Sodium chloride 
Water for injections 
 
6.2 Incompatibilities 
 
None known. 
 



16 

6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C to 8°C). 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
A single Benlysta pre-filled syringe or pre-filled pen can be stored at temperatures up to a maximum of 25°C 
for a period of up to 12 hours. The syringe or pen must be protected from light, and discarded if not used 
within the 12 hour period. 
 
6.5 Nature and contents of container 
 
 
Pre-filled pen 
 
1 ml solution in a type 1 glass syringe with a fixed needle (stainless steel) in a pre-filled pen. 
 
Available in packs of 1 or 4 pre-filled pens and multipack containing 12 single-dose pre-filled pens (3 packs 
of 4 pre-filled pens). 
 
Not all pack sizes may be marketed. 
 
Pre-filled syringe 
 
1 ml solution in a type 1 glass syringe with a fixed needle (stainless steel) and needle cap. 
 
Available in pack of 1 pre-filled syringe and pack of 4 pre-filled syringes. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Comprehensive instructions for subcutaneous administration of Benlysta in a pre-filled pen or pre-filled 
syringe are provided at the end of the package leaflet (see Step-by-step instructions). 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline (Ireland) Limited  
12 Riverwalk  
Citywest Business Campus 
Dublin 24 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/700/003 1 pre-filled pen 
EU/1/11/700/004 4 pre-filled pens 
EU/1/11/700/005 12 (3x4) pre-filled pens (multipack) 



17 

EU/1/11/700/006 1 pre-filled syringe 
EU/1/11/700/007 4 pre-filled syringes 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 13 July 2011 
Date of latest renewal: 18 February 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/


18 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 
safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 
4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Benlysta 120 mg powder for concentrate for solution for infusion. 
Benlysta 400 mg powder for concentrate for solution for infusion. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Benlysta 120 mg powder for concentrate for solution for infusion. 
Each vial contains 120 mg of belimumab. After reconstitution, the solution contains 80 mg belimumab per 
ml. 
 
Benlysta 400 mg powder for concentrate for solution for infusion. 
Each vial contains 400 mg of belimumab. After reconstitution, the solution contains 80 mg belimumab per 
ml. 
 
Belimumab is a human, IgG1λ monoclonal antibody, produced in a mammalian cell line (NS0) by 
recombinant DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for concentrate for solution for infusion. 
White to off-white powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Benlysta is indicated as add-on therapy in patients aged 5 years and older with active, autoantibody-positive 
systemic lupus erythematosus (SLE) with a high degree of disease activity (e.g., positive anti-dsDNA and 
low complement) despite standard therapy (see section 5.1). 
 
4.2 Posology and method of administration 
 
Benlysta treatment should be initiated and supervised by a qualified physician experienced in the diagnosis 
and treatment of SLE. Benlysta infusions should be administered by a qualified healthcare professional 
trained to give infusion therapy. 
 
Administration of Benlysta may result in severe or life-threatening hypersensitivity reactions and infusion 
reactions. Patients have been reported to develop symptoms of acute hypersensitivity several hours after the 
infusion has been administered. Recurrence of clinically significant reactions after initial appropriate 
treatment of symptoms has also been observed (see sections 4.4 and 4.8). Therefore, Benlysta should be 
administered in an environment where resources for managing such reactions are immediately available. 
Patients should remain under clinical supervision for a prolonged period of time (for several hours), 
following at least the first 2 infusions, taking into account the possibility of a late onset reaction. 
 



19 

Patients treated with Benlysta should be made aware of the potential risk of severe or life-threatening 
hypersensitivity and the potential for delayed onset or recurrence of symptoms. The package leaflet should 
be provided to the patient each time Benlysta is administered (see section 4.4). 
 
Posology 
 
Premedication including an antihistamine, with or without an antipyretic, may be administered before the 
infusion of Benlysta (see section 4.4). 
 
The recommended dose regimen is 10 mg/kg Benlysta on Days 0, 14 and 28, and at 4-week intervals 
thereafter. The patient’s condition should be evaluated continuously. Discontinuation of treatment with 
Benlysta should be considered if there is no improvement in disease control after 6 months of treatment. 
 
Transition from intravenous to subcutaneous administration 
 
If a patient is being transitioned from Benlysta intravenous administration to subcutaneous administration, 
the first subcutaneous injection should be administered 1 to 4 weeks after the last intravenous dose (see 
section 5.2). 
 
Special populations 
 
Elderly 
Data on patients ≥65 years are limited (see section 5.1). Benlysta should be used with caution in the elderly. 
Dose adjustment is not required (see section 5.2). 
 
Renal impairment 
Belimumab has been studied in a limited number of SLE patients with renal impairment. 
On the basis of the available information, dose adjustment is not required in patients with mild, moderate or 
severe renal impairment. Caution is however recommended in patients with severe renal impairment due to 
the lack of data (see section 5.2). 
 
Hepatic impairment 
No specific studies with Benlysta have been conducted in patients with hepatic impairment. Patients with 
hepatic impairment are unlikely to require dose adjustment (see section 5.2). 
 
Paediatric population 
The recommended dose regimen for children aged 5 years and older is 10 mg/kg Benlysta on Days 0, 14 and 
28, and at 4-week intervals thereafter. 
 
The safety and efficacy of Benlysta in children aged below 5 years has not been established. No data are 
available. 
 
Method of administration  
 
Benlysta is administered intravenously by infusion, and must be reconstituted and diluted before 
administration. For instructions on reconstitution, dilution, and storage of the medicinal product before 
administration, see section 6.6. 
 
Benlysta should be infused over a 1-hour period. 
 
Benlysta must not be administered as an intravenous bolus. 
 
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 potentially life-threatening adverse reaction 
(see sections 4.4 and 4.8). 
 



20 

4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve traceability of biological medicinal products, the tradename and the batch number of the 
administered product should be clearly recorded. 
 
Benlysta has not been studied in the following adult and paediatric patient groups, and is not recommended 
in: 
 

• severe active central nervous system lupus 
 

• severe active lupus nephritis (see section 5.1) 
 

• HIV 
 

• a history of, or current, hepatitis B or C 
 

• hypogammaglobulinaemia (IgG <400 mg/dl) or IgA deficiency (IgA <10 mg/dl) 
 

• a history of major organ transplant or hematopoietic stem cell /marrow transplant or renal 
transplant. 

 
Concomitant use with B cell targeted therapy or cyclophosphamide 
 
Benlysta has not been studied in combination with other B cell targeted therapy or intravenous 
cyclophosphamide. Caution should be exercised if Benlysta is co-administered with other B cell targeted 
therapy or cyclophosphamide. 
 
Infusion reactions and hypersensitivity 
 
Administration of Benlysta may result in hypersensitivity reactions and infusion reactions which can be 
severe, and fatal. In the event of a severe reaction, Benlysta administration must be interrupted and 
appropriate medical therapy administered (see section 4.2). The risk of hypersensitivity reactions is greatest 
with the first two infusions; however the risk should be considered for every infusion administered. Patients 
with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. 
 
Premedication including an antihistamine, with or without an antipyretic, may be administered before the 
infusion of Benlysta. There is insufficient knowledge to determine whether premedication could diminish the 
frequency or severity of infusion reactions. 
 
In clinical studies, serious infusion and hypersensitivity reactions affected approximately 0.9% of adult 
patients, and included anaphylactic reaction, bradycardia, hypotension, angioedema, and dyspnoea. Infusion 
reactions occurred more frequently during the first two infusions and tended to decrease with subsequent 
infusions (see section 4.8). Patients have been reported to develop symptoms of acute hypersensitivity 
several hours after the infusion has been administered. Recurrence of clinically significant reactions after 
initial appropriate treatment of symptoms has also been observed (see sections 4.2 and 4.8). Therefore, 
Benlysta should be administered in an environment where resources for managing such reactions are 
immediately available. Patients should remain under clinical supervision for a prolonged period of time (for 
several hours), following at least the first 2 infusions, taking into account the possibility of a late onset 
reaction. Patients should be advised that hypersensitivity reactions are possible, on the day of, or several days 
after infusion, and be informed of potential signs and symptoms and the possibility of recurrence. Patients 



21 

should be instructed to seek immediate medical attention if they experience any of these symptoms. The 
package leaflet should be provided to the patient each time Benlysta is administered (see section 4.2). 
 
Delayed-type, non-acute hypersensitivity reactions have also been observed and included symptoms such as 
rash, nausea, fatigue, myalgia, headache, and facial oedema. 
 
Infections 
 
The mechanism of action of belimumab could increase the risk for the development of infections in adults 
and children with lupus, including opportunistic infections, and younger children may be at increased risk. In 
controlled clinical studies, the incidence of serious infections was similar across the Benlysta and placebo 
groups; however, fatal infections (e.g. pneumonia and sepsis) occurred more frequently in patients receiving 
Benlysta compared with placebo (see section 4.8). Pneumococcal vaccination should be considered before 
initiating Benlysta treatment. Benlysta should not be initiated in patients with active serious infections 
(including serious chronic infections). Physicians should exercise caution and carefully assess if the benefits 
are expected to outweigh the risks when considering the use of Benlysta in patients with a history of 
recurrent infection. Physicians should advise patients to contact their health care provider if they develop 
symptoms of an infection. Patients who develop an infection while undergoing treatment with Benlysta 
should be monitored closely and careful consideration given to interrupting immunosuppressant therapy 
including Benlysta until the infection is resolved. The risk of using Benlysta in patients with active or latent 
tuberculosis is unknown. 
 
Depression and suicidality 
 
In controlled clinical intravenous and subcutaneous studies, psychiatric disorders (depression, suicidal 
ideation and behaviour including suicides) have been reported more frequently in patients receiving Benlysta 
(see section 4.8). Physicians should assess the risk of depression and suicide considering the patient’s 
medical history and current psychiatric status before treatment with Benlysta and continue to monitor 
patients during treatment. Physicians should advise patients (and caregivers where appropriate) to contact 
their health care provider about new or worsening psychiatric symptoms. In patients who experience such 
symptoms, treatment discontinuation should be considered. 
 
Progressive multifocal leukoencephalopathy  
 
Progressive multifocal leukoencephalopathy (PML) has been reported with Benlysta treatment for SLE. 
Physicians should be particularly alert to symptoms suggestive of PML that patients may not notice (e.g., 
cognitive, neurological or psychiatric symptoms or signs). Patients should be monitored for any of these new 
or worsening symptoms or signs, and if such symptoms/signs occur, referral to a neurologist and appropriate 
diagnostic measures for PML should be considered. If PML is suspected, further dosing must be suspended 
until PML has been excluded. 
 
Immunisation 
 
Live vaccines should not be given for 30 days before, or concurrently with Benlysta, as clinical safety has 
not been established. No data are available on the secondary transmission of infection from persons receiving 
live vaccines to patients receiving Benlysta. 
 
Because of its mechanism of action, belimumab may interfere with the response to immunisations. However, 
in a small study evaluating the response to a 23-valent pneumococcal vaccine, overall immune responses to 
the different serotypes were similar in SLE patients receiving Benlysta compared with those receiving 
standard immunosuppressive treatment at the time of vaccination. There are insufficient data to draw 
conclusions regarding response to other vaccines. 
 
Limited data suggest that Benlysta does not significantly affect the ability to maintain a protective immune 
response to immunisations received prior to administration of Benlysta. In a substudy, a small group of 
patients who had previously received either tetanus, pneumococcal or influenza vaccinations were found to 
maintain protective titres after treatment with Benlysta. 



22 

 
Malignancies and lymphoproliferative disorders 
 
Immunomodulatory medicinal products, including Benlysta, may increase the risk of malignancy. Caution 
should be exercised when considering Benlysta therapy for patients with a history of malignancy or when 
considering continuing treatment in patients who develop malignancy. Patients with malignant neoplasm 
within the last 5 years have not been studied, with the exception of those with basal or squamous cell cancers 
of the skin, or cancer of the uterine cervix, that has been fully excised or adequately treated. 
 
Sodium content 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No in vivo interaction studies have been performed. The formation of some CYP450 enzymes is suppressed 
by increased levels of certain cytokines during chronic inflammation. It is not known if belimumab could be 
an indirect modulator of such cytokines. A risk for indirect reduction of CYP activity by belimumab cannot 
be excluded. On initiation or discontinuation of belimumab, therapeutic monitoring should be considered for 
patients being treated with CYP substrates with a narrow therapeutic index, where the dose is individually 
adjusted (e.g. warfarin). 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/Contraception in males and females 
 
Women of childbearing potential must use effective contraception during Benlysta treatment and for at least 
4 months after the last treatment. 
 
Pregnancy 
 
There are a limited amount of data from the use of Benlysta in pregnant women. No formal studies have 
been conducted. Besides an expected pharmacological effect i.e. reduction of B cells, animal studies in 
monkeys do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 
5.3). 
Benlysta should not be used during pregnancy unless the potential benefit justifies the potential risk to the 
foetus. 
 
Breast-feeding 
 
It is unknown whether Benlysta is excreted in human milk or is absorbed systemically after ingestion. 
However, belimumab was detected in the milk from female monkeys administered 150 mg/kg every 2 
weeks. 
 
Because maternal antibodies (IgG) are excreted in breast milk, it is recommended that a decision should be 
made whether to discontinue breast-feeding or to discontinue Benlysta therapy, taking into account the 
benefit of breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
There are no data on the effects of belimumab on human fertility. Effects on male and female fertility have 
not been formally evaluated in animal studies (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. No detrimental 
effects on such activities are predicted from the pharmacology of belimumab. The clinical status of the 



23 

subject and the adverse reaction profile of Benlysta should be borne in mind when considering the patient's 
ability to perform tasks that require judgement, motor or cognitive skills. 
 
4.8 Undesirable effects 
 
Summary of the safety profile in adults 
 
The safety of belimumab in patients with SLE has been evaluated in 3 pre-registration, placebo-controlled 
intravenous studies, 1 placebo-controlled subcutaneous study, and one post-marketing, placebo-controlled 
intravenous study. 
 
The data presented in the table below reflect exposure to Benlysta administered (10 mg/kg intravenously 
over a 1-hour period on Days 0, 14, 28, and then every 28 days for up to 52 weeks) in 674 patients with SLE, 
including 472 exposed for at least 52 weeks, and 556 patients exposed to 200 mg Benlysta subcutaneously 
once weekly for up to 52 weeks. The safety data presented include data beyond Week 52 in some patients. 
Data from post-marketing reports are also included. 
 
The majority of patients were also receiving one or more of the following concomitant treatments for SLE: 
corticosteroids, immunomodulatory medicinal products, anti-malarials, non-steroidal anti-inflammatory 
medicinal products. 
 
Adverse reactions were reported in 87% of Benlysta-treated patients and 90% of placebo-treated patients. 
The most frequently reported adverse reactions (≥5% of patients with SLE treated with Benlysta plus 
standard of care and at a rate ≥1% greater than placebo) were viral upper respiratory tract infections, 
bronchitis, and diarrhoea. The proportion of patients who discontinued treatment due to adverse reactions 
was 7% for Benlysta-treated patients and 8% for placebo-treated patients. 
 
Tabulated list of adverse reactions 
 
Adverse reactions are listed below by MedDRA system organ class and by frequency. The frequency 
categories used are: 
 
Very common  ≥1/10 
Common  ≥1/100 to <1/10 
Uncommon  ≥1/1,000 to <1/100 
Rare    ≥1/10,000 to <1/1000 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The 
frequency given is the highest seen with either formulation. 
 

System organ class Frequency 
 

Adverse reaction(s) 

Infections and infestations1 Very common Bacterial infections, e.g. bronchitis, 
urinary tract infection 
 

Common Gastroenteritis viral, pharyngitis, 
nasopharyngitis, viral upper 
respiratory tract infection 
 

Blood and lymphatic system 
disorders 
 

Common Leucopenia 

Immune system disorders 
 

Common 
 

Hypersensitivity reactions2 

Uncommon Anaphylactic reaction 
 

 Rare Delayed-type, non-acute 



24 

hypersensitivity reactions 
 

Psychiatric disorders 
 

Common Depression 
Uncommon 
 

Suicidal behaviour, suicidal ideation 
 

Nervous system disorders 
 

Common Migraine 

Gastrointestinal disorders Very common Diarrhoea, nausea 
 

Skin and subcutaneous tissue 
disorders 
 

Common Injection site reactions3 
 

Uncommon Angioedema, urticaria, rash  
 

Musculoskeletal and 
connective tissue disorders 
 

Common Pain in extremity 

General disorders and 
administration site conditions 
 

Common Infusion or injection-related systemic 
reactions2, pyrexia 
 

1 See ‘Description of selected adverse reactions’ and section 4.4 ‘Infections’ for further information.  
2 ‘Hypersensitivity reactions’ covers a group of terms, including anaphylaxis, and can manifest as a range of 
symptoms including hypotension, angioedema, urticaria or other rash, pruritus, and dyspnoea. ‘Infusion or 
injection-related systemic reactions’ covers a group of terms and can manifest as a range of symptoms 
including bradycardia, myalgia, headache, rash, urticaria, pyrexia, hypotension, hypertension, dizziness, and 
arthralgia. Due to overlap in signs and symptoms, it is not possible to distinguish between hypersensitivity 
reactions and infusion reactions in all cases. 
3 Applies to subcutaneous formulation only. 
 
Description of selected adverse reactions 
 
Data presented below are pooled from the intravenous clinical studies (10 mg/kg intravenous dose only) and 
the subcutaneous clinical study. ‘Infections’ and ‘Psychiatric disorders’ also include data from a 
post-marketing study. 
 
Infusion or injection-related systemic reactions and hypersensitivity: Infusion or injection-related systemic 
reactions and hypersensitivity were generally observed on the day of administration, but acute 
hypersensitivity reactions may also occur several days after dosing. Patients with a history of multiple drug 
allergies or significant hypersensitivity reactions may be at increased risk. 
 
The incidence of infusion reactions and hypersensitivity reactions after intravenous administration occurring 
within 3 days of an infusion was 12% in the group receiving Benlysta and 10% in the group receiving 
placebo, with 1.2% and 0.3%, respectively, requiring permanent treatment discontinuation. 
 
Infections: The overall incidence of infections in intravenous and subcutaneous pre-registration studies was 
63% in both groups receiving Benlysta or placebo. Infections occurring in at least 3% of patients receiving 
Benlysta and at least 1% more frequently than patients receiving placebo were viral upper respiratory tract 
infection, bronchitis, and urinary tract infection bacterial. Serious infections occurred in 5% of patients in 
both groups receiving Benlysta or placebo; serious opportunistic infections accounted for 0.4% and 0% of 
these, respectively. Infections leading to discontinuation of treatment occurred in 0.7% of patients receiving 
Benlysta and 1.5% of patients receiving placebo. Some infections were severe or fatal. 
 
For information on infections observed in paediatric patients see Paediatric population section below. 
 
In a randomised, double-blind, 52-week, post-marketing safety study (BEL115467) which assessed mortality 
and specific adverse events in adults, serious infections occurred in 3.7% of patients receiving Benlysta 
(10 mg/kg intravenously) vs 4.1% of patients receiving placebo. However, fatal infections (e.g. pneumonia 



25 

and sepsis) occurred in 0.45% (9/2002) of Benlysta-treated patients vs 0.15% (3/2001) of patients receiving 
placebo, while the incidence of all-cause mortality was 0.50% (10/2002) vs 0.40% (8/2001), respectively. 
Most fatal infections were observed during the first 20 weeks of treatment with Benlysta. 
 
Psychiatric disorders: In the pre-registration intravenous clinical studies, serious psychiatric events were 
reported in 1.2% (8/674) of patients receiving Benlysta 10 mg/kg and 0.4% (3/675) of patients receiving 
placebo. Serious depression was reported in 0.6% (4/674) of patients receiving Benlysta 10 mg/kg and 0.3% 
(2/675) of patients receiving placebo. There were two suicides in Benlysta-treated patients (including one 
receiving 1 mg/kg Benlysta). 
 
In a post-marketing study, serious psychiatric events were reported in 1.0% (20/2002) of patients receiving 
Benlysta and 0.3% (6/2001) of patients receiving placebo. Serious depression was reported in 0.3% (7/2002) 
of patients receiving Benlysta and <0.1% (1/2001) of patients receiving placebo. The overall incidence of 
serious suicidal ideation or behaviour or self-injury without suicidal intent was 0.7% (15/2002) in patients 
receiving Benlysta and 0.2% (5/2001) in the placebo group. No suicide was reported in either group. 
 
The intravenous studies did not exclude patients with a history of psychiatric disorders. 
 
In the subcutaneous clinical study, which excluded patients with a history of psychiatric disorders, 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. 
 
Leucopenia: The incidence of leucopenia reported as an adverse event was 3% in the group receiving 
Benlysta and 2% in the group receiving placebo. 
 
Gastrointestinal disorders: Obese patients [Body mass index (BMI) >30 kg/m2] treated with intravenously 
administered. Benlysta reported higher rates of nausea, vomiting and diarrhoea relative to placebo, and 
compared with normal-weight patients (BMI ≥18.5 to ≤30 kg/m2). None of these gastrointestinal events in 
obese patients were serious. 
 
Paediatric population 
 
The adverse reaction profile in paediatric patients is based on 52-week safety data from a placebo-controlled 
study in which 53 patients (6 to 17 years of age) with SLE received Benlysta (10 mg/kg intravenously on 
Days 0, 14, 28, and then every 28 days, on a background of concomitant treatments). No new safety signals 
were observed in the paediatric population 12 years of age and above (n=43). Safety data in children younger 
than 12 years of age (n=10) are limited. 
 
Infections 
5- to 11-year-old group: infections were reported in 8/10 patients receiving Benlysta and 3/3 patients 
receiving placebo, and serious infections were reported in 1/10 patients receiving Benlysta and 2/3 patients 
receiving placebo (see section 4.4). 
12- to 17-year-old group: infections were reported in 22/43 patients receiving Benlysta and 25/37 patients 
receiving placebo, and serious infections were reported in 3/43 patients receiving Benlysta and 3/37 patients 
receiving placebo. In the open-label extension phase there was one fatal infection in a patient receiving 
Benlysta. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 
to report any suspected adverse reactions via the national reporting system listed in Appendix V. 
 
4.9 Overdose 
 
There is limited clinical experience with overdose of Benlysta.  Adverse reactions reported in association 
with cases of overdose have been consistent with those expected for belimumab. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


26 

 
Two doses up to 20 mg/kg administered 21 days apart by intravenous infusion have been given to humans 
with no increase in incidence or severity of adverse reactions compared with doses of 1, 4, or 10 mg/kg. 
 
In the case of inadvertent overdose, patients should be carefully observed and supportive care administered, 
as appropriate. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Selective immunosuppressants, ATC code: L04AA26 
 
Mechanism of action 
 
Belimumab is a human IgG1λ monoclonal antibody specific for soluble human B Lymphocyte Stimulator 
protein (BLyS, also referred to as BAFF and TNFSF13B). Belimumab blocks the binding of soluble BLyS, a 
B cell survival factor, to its receptors on B cells. Belimumab does not bind B cells directly, but by binding 
BLyS, belimumab inhibits the survival of B cells, including autoreactive B cells, and reduces the 
differentiation of B cells into immunoglobulin-producing plasma cells. 
 
BLyS levels are elevated in patients with SLE and other autoimmune diseases. There is an association 
between plasma BLyS levels and SLE disease activity. The relative contribution of BLyS levels to the 
pathophysiology of SLE is not fully understood. 
 
Pharmacodynamic effects 
 
Changes in biomarkers were seen in clinical trials with Benlysta administered intravenously. In adult patients 
with hypergammaglobulinemia, normalization of IgG levels was observed by Week 52 in 49% and 20% of 
patients receiving Benlysta and placebo, respectively. 
 
In patients with anti-dsDNA antibodies, 16% of patients treated with Benlysta converted to anti-dsDNA 
negative compared with 7% of the patients receiving placebo by Week 52. 
 
In patients with low complement levels, normalization of C3 and C4 was observed by Week 52 in 38% and 
44% of patients receiving Benlysta and in 17% and 18% of patients receiving placebo, respectively. 
 
Of the anti-phospholipid antibodies, only anti-cardiolipin antibody was measured. For anti-cardiolipin IgA 
antibody a 37% reduction at Week 52 was seen (p=0.0003), for anti-cardiolipin IgG antibody a 26% 
reduction at Week 52 was seen (p=0.0324) and for anti-cardiolipin IgM a 25% reduction was seen (p=NS, 
0.46). 
 
Changes in B cells (including naïve, memory and activated B cells, and plasma cells) and IgG levels 
occurring in patients during ongoing treatment with intravenous belimumab were followed in a long-term 
uncontrolled extension study. After 7 and a half years of treatment (including the 72-week parent study), a 
substantial and sustained decrease in various B cell subsets was observed leading to 87% median reduction 
in naïve B cells, 67% in memory B cells, 99% in activated B cells, and 92% median reduction in plasma cells 
after more than 7 years of treatment. After about 7 years, a 28% median reduction in IgG levels was 
observed, with 1.6% of subjects experiencing a decrease in IgG levels to below 400 mg/dl. Over the course 
of the study, the reported incidence of AEs generally remained stable or declined. 
 
In one study in paediatric patients (6 to 17 years of age) the pharmacodynamic response was consistent with 
the adult data. 
 



27 

Immunogenicity 
 
Assay sensitivity for neutralising antibodies and non-specific anti-drug antibody (ADA) is limited by the 
presence of active drug in the collected samples. The true occurrence of neutralising antibodies and 
non-specific anti-drug antibody in the study population is therefore not known. In the two Phase III studies in 
adults, 4 of the 563 (0.7%) patients in the 10 mg/kg group and 27 out of 559 (4.8%) patients in the 1 mg/kg 
group tested positive for persistent presence of anti-belimumab antibodies. Among persistent-positive 
subjects in the Phase III studies, 1/10 (10%), 2/27 (7%) and 1/4 (25%) subjects in the placebo, 1 mg/kg and 
10 mg/kg groups, respectively, experienced infusion reactions on a dosing day; these infusion reactions were 
all non-serious and mild to moderate in severity. Few patients with ADA reported serious/severe AEs. The 
rates of infusion reactions among persistent-positive subjects were comparable to the rates for ADA negative 
patients of 75/552 (14%), 78/523 (15%), and 83/559 (15%) in the placebo, 1 mg/kg and 10 mg/kg groups, 
respectively. 
 
In one study in 6 to 17-year-old paediatric patients (n=53), none of the patients developed anti-belimumab 
antibodies. 
 
Clinical efficacy and safety 
 
Intravenous infusion in adults 
The efficacy of Benlysta administered intravenously was evaluated in 2 randomized, double-blind, 
placebo-controlled studies in 1,684 patients with a clinical diagnosis of SLE according to the American 
College of Rheumatology (ACR) classification criteria. Patients had active SLE disease, defined as a 
SELENA-SLEDAI (SELENA=Safety of Estrogens in Systemic Lupus Erythematosus National Assessment; 
SLEDAI=Systemic Lupus Erythematosus Disease Activity Index) score ≥6 and positive anti-nuclear 
antibody (ANA) test results (ANA titre ≥1:80 and/or a positive anti-dsDNA [≥30 units/ml]) at screening. 
Patients were on a stable SLE treatment regimen consisting of (alone or in combination): corticosteroids, 
anti-malarials, NSAIDs or other immunosuppressives. The two studies were similar in design except that 
BLISS-76 was a 76-week study and BLISS-52 was a 52-week study. In both studies the primary efficacy 
endpoint was evaluated at 52 weeks. 
 
Patients who had severe active lupus nephritis and patients who had severe active central nervous system 
(CNS) lupus were excluded. 
 
BLISS-76 was conducted primarily in North America and Western Europe. Background medicinal products 
included corticosteroids (76%; >7.5 mg/day 46%), immunosuppressives (56%), and anti-malarials (63%). 
 
BLISS-52 was conducted in South America, Eastern Europe, Asia, and Australia. Background medicinal 
products included corticosteroids (96%; >7.5 mg/day 69%), immunosuppressives (42%), and anti-malarials 
(67%). 
 
At baseline 52% of patients had high disease activity (SELENA SLEDAI score ≥10), 59% of patients had 
mucocutaneous, 60% had musculoskeletal, 16% had haematological, 11% had renal and 9% had vascular 
organ domain involvement (BILAG A or B at baseline). 
 
The primary efficacy endpoint was a composite endpoint (SLE Responder Index) 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 score (PGA) 
 
The SLE Responder Index measures improvement in SLE disease activity, without worsening in any organ 
system, or in the patient’s overall condition. 
 



28 

Table 1: Response rate at week 52 

Response 
 

BLISS-76 BLISS-52 BLISS-76 and BLISS-52  
Pooled  

Placebo* 
 
(n=275) 
 

Benlysta 
10 mg/kg* 

(n=273) 
 

Placebo* 
 
(n=287) 
 

Benlysta 
10 mg/kg* 

(n=290) 

Placebo* 
 

(n=562) 

Benlysta 
10 mg/kg* 

(n=563) 
 

SLE responder 
index 
 
Observed 
difference vs 
placebo 
 
Odds ratio 
(95% CI) vs 
placebo 
 

33.8% 43.2% 
(p=0.021) 

 
 

9.4% 
 
 

 
1.52 

(1.07, 2.15) 

43.6% 57.6% 
(p=0.0006) 

 
 

14.0% 
 
 
 

1.83 
(1.30,2.59) 

38.8% 50.6% 
(p<0.0001) 

 
 

11.8% 
 
 
 

1.68 
(1.32,2.15) 

Components of SLE responder index 
 
Percent of 
patients with 
reduction in 
SELENA- 
SLEDAI ≥4 

35.6% 46.9% 
(p=0.006) 

46.0% 58.3% 
(p= 0.0024) 

40.9% 52.8% 
(p<0.0001) 

Percent of 
patients with 
no worsening 
by BILAG 
index 

65.1% 69.2% 
(p=0.32) 

73.2% 81.4% 
(p=0.018) 

69.2% 75.5% 
(p=0.019) 

Percent of 
patients with 
no worsening 
by PGA  

62.9% 69.2% 
(p=0.13) 

69.3% 79.7% 
(p=0.0048) 

66.2% 74.6% 
(p=0.0017) 

* All patients received standard therapy 
 
In a pooled analysis of the two studies, the percentage of patients receiving >7.5 mg/day prednisone (or 
equivalent) at baseline, whose average corticosteroid dose was reduced by at least 25% to a dose equivalent 
to prednisone ≤7.5 mg/day during Weeks 40 through 52, was 17.9% in the group receiving Benlysta and 
12.3% in the group receiving placebo (p=0.0451). 
 
Flares in SLE were defined by the modified SELENA SLEDAI SLE Flare Index. The median time to the 
first flare was delayed in the pooled group receiving Benlysta compared to the group receiving placebo (110 
vs 84 days, hazard ratio=0.84, p=0.012). Severe flares were observed in 15.6% of the Benlysta group 
compared to 23.7% of the placebo group over the 52 weeks of observation (observed treatment difference = -
8.1%; hazard ratio=0.64, p=0.0011). 
 
Benlysta demonstrated improvement in fatigue compared with placebo measured by the FACIT-Fatigue 
scale in the pooled analysis. The mean change of score at Week 52 from baseline is significantly greater with 
Benlysta compared to placebo (4.70 vs 2.46, p=0.0006). 
 
Univariate and multivariate analysis of the primary endpoint in pre-specified subgroups demonstrated that 
the greatest benefit was observed in patients with higher disease activity including patients with SELENA 
SLEDAI scores ≥ 10, or patients requiring steroids to control their disease, or patients with low complement 
levels. 
 



29 

Post-hoc analysis has identified high responding subgroups such as those patients with low complement and 
positive anti-dsDNA at baseline, see Table 2 for results of this example of a higher disease activity group. 
Of these patients, 64.5% had SELENA SLEDAI scores ≥ 10 at baseline. 
 
Table 2: Patients with low complement and positive anti-dsDNA at baseline 
 

Subgroup  Anti-dsDNA positive AND low complement 
 

BLISS-76 and BLISS-52 pooled data 
 

Placebo 
 

(n=287) 

Benlysta 
10 mg/kg 
(n=305) 

SRI response rate at week 52 (%) 
 
Observed treatment difference vs placebo (%) 

31.7 51.5 (p<0.0001) 
 

19.8 
SRI response rate (excluding complement and 
anti-dsDNA changes) at week 52 (%) 
 
Observed treatment difference vs placebo (%) 

28.9 46.2 (p<0.0001) 
 

 
17.3 

 
Severe flares over 52 weeks 
 
Patients experiencing a severe flare (%) 
 
Observed treatment difference vs. placebo (%) 
Time to severe flare [Hazard ratio (95% CI)] 

 
 

29.6 

 
 

19.0 
 

10.6 
0.61 (0.44, 0.85) 

(p=0.0038) 
 

Prednisone reduction by ≥25% from baseline 
to ≤7.5 mg/day during weeks 40 through 52* 
(%)  
 
Observed treatment difference vs placebo (%) 

(n=173) 
12.1 

(n=195) 
18.5 (p=0.0964) 

 
 

6.3 
 

FACIT-fatigue score improvement from 
baseline at week-52 (mean) 
 
Observed treatment difference vs placebo 
(mean difference) 

1.99 4.21 (p=0.0048) 
 
 

2.21 

 
 
BLISS-76 Study only 

 
 

Placebo 
(n=131) 

 
 

Benlysta 
10 mg/kg 
(n=134) 

SRI response rate at week-76 (%) 
 
Observed treatment difference vs placebo (%) 

27.5 39.6 (p=0.0160) 
 

12.1 
 

* Among patients with baseline prednisone dose >7.5 mg/day 
 

Age and race 
 
Age 
 There were no observed differences in efficacy or safety in patients ≥65 years who received Benlysta 
intravenously or subcutaneously compared to the overall population in placebo-controlled studies; however, 
the number of patients aged ≥65 years (62 patients for efficacy and 219 for safety) is not sufficient to 



30 

determine whether they respond differently to younger patients. 
 
Black patients 
Benlysta was administered intravenously to black patients in a randomised (2:1), double-blind, 
placebo-controlled, 52-week Phase III/IV study (EMBRACE). Efficacy was evaluated in 448 patients. The 
proportion of black patients achieving an SRI-S2K response was higher in patients receiving Benlysta but the 
difference was not statistically significant compared with placebo. However, consistent with results from 
other studies, in black patients with high disease activity (low complement and positive anti-dsDNA at 
baseline, n=141) the SRI-S2K response was 45.1% for Benlysta 10 mg/kg compared with 24.0% for placebo 
(odds ratio 3.00; 95% CI: 1.35, 6.68). 
 
Paediatric population 
 
The safety and efficacy of Benlysta was evaluated in a randomised, double-blind, placebo-controlled, 
52-week study (PLUTO) in 93 paediatric patients with a clinical diagnosis of SLE according to the ACR 
classification criteria. Patients had active SLE disease, defined as a SELENA-SLEDAI score ≥6 and positive 
autoantibodies at screening as described in the adult trials. Patients were on a stable SLE treatment regimen 
(standard of care) and had similar inclusion criteria as the adult studies. Patients who had severe active lupus 
nephritis, severe active CNS lupus, primary immunodeficiency, IgA deficiency or acute or chronic infections 
requiring management were excluded from the study. The study was conducted in the US, South America, 
Europe, and Asia. Patient median age was 15 years (range 6 to 17 years). In the 5- to 11-year-old-group 
(n=13) the SELENA-SLEDAI score ranged from 4 to 13, and in 12- to 17-year-old-group (n=79) the 
SELENA-SLEDAI score ranged from 4 to 20. The majority (94.6%) of patients were female. The study was 
not powered for any statistical comparisons and all data are descriptive. 
 
The primary efficacy endpoint was the SLE Responder Index (SRI) at Week 52 as described in the adult 
intravenous trials. There was a higher proportion of paediatric patients achieving an SRI response in patients 
receiving Benlysta compared with placebo. The response for the individual components of the endpoint were 
consistent with that of the SRI (Table 3). 
 
Table 3 – Paediatric response rate at Week 52 
 
Response Placebo 

 
(n=40) 

Benlysta 
10 mg/kg 

(n=53) 

SLE Responder Index (%) 
 
 
Odds ratio (95% CI) vs placebo 
 

43.6 
(17/39) 

52.8 
(28/53) 

 
1.49 (0.64, 3.46) 

Components of SLE Responder Index 
 
Percent of patients with reduction in SELENA-SLEDAI ≥4 (%) 
 
Odds ratio (95% CI) vs placebo 

43.6 
(17/39) 

54.7 
(29/53) 

 
1.62 (0.69, 3.78) 

Percent of patients with no worsening by BILAG index (%) 
 
Odds ratio (95% CI) vs placebo 

61.5 
(24/39) 

73.6 
(39/53) 

 
1.96 (0.77, 4.97) 

Percent of patients with no worsening by PGA (%) 
 
Odds ratio (95% CI) vs placebo 

66.7 
(26/39) 

75.5 
(40/53) 

 
1.70 (0.66, 4.39) 

 



31 

Among patients experiencing a severe flare, the median study day of the first severe flare was Day 150 in the 
Benlysta group and Day 113 in the placebo group. Severe flares were observed in 17.0% of the Benlysta 
group compared to 35.0% of the placebo group over the 52 weeks of observation (observed treatment 
difference = 18.0%; hazard ratio = 0.36, 95% CI: 0.15, 0.86). This was consistent with the findings from the 
adult intravenous clinical trials. 
 
Using the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology 
(PRINTO/ACR) Juvenile SLE Response Evaluation Criteria, a higher proportion of paediatric patients 
receiving Benlysta demonstrated improvement compared with placebo (Table 4). 
 
Table 4 – PRINTO/ACR response rate at Week 52 
 

 Proportion of patients with at 
least 50% improvement in any 

2 of 5 components* and no 
more than one of the remaining 
worsening by more than 30% 

 

Proportion of patients with at 
least 30% improvement in 3 of 

5 components* and no more 
than one of the remaining 
worsening more than 30% 

 
 Placebo 

 
n=40 

Benlysta 
10 mg/kg 

n=53 

Placebo 
 

n=40 

Benlysta 
10 mg/kg 

n=53 
Response, n (%) 
 

14/40  
(35.0) 

 

32/53 
(60.4) 

11/40 
(27.5) 

28/53 
(52.8) 

Observed difference vs Placebo 
 

 25.38  25.33 

Odds ratio (95% CI) vs Placebo 
 

 2.74 
(1.15, 6.54) 

 2.92 
(1.19, 7.17) 

*The five PRINTO/ACR components were percent change at Week 52 in: Parent’s Global Assessment (Parent 
GA), PGA, SELENA SLEDAI score, 24-hour proteinuria, and, Paediatric Quality of Life Inventory – Generic 
Core Scale (PedsQL GC) physical functioning domain score. 
 
5.2 Pharmacokinetic properties 
 
The intravenous pharmacokinetic parameters quoted below are based on population parameter estimates for 
the 563 patients who received Benlysta 10 mg/kg in the two Phase III studies. 
 
Absorption 
 
Benlysta is administered by intravenous infusion. Maximum serum concentrations of belimumab were 
generally observed at, or shortly after, the end of the infusion. The maximum serum concentration was 
313 µg/ml (range: 173-573 µg/ml) based on simulating the concentration time profile using the typical 
parameter values of the population pharmacokinetic model. 
 
Distribution 
 
Belimumab was distributed to tissues with steady-state volume (Vss) of distribution of approximately 
5 litres. 
 
Biotransformation 
 
Belimumab is a protein for which the expected metabolic pathway is degradation to small peptides and 
individual amino acids by widely distributed proteolytic enzymes. Classical biotransformation studies have 
not been conducted. 
 



32 

Elimination 
 
Serum belimumab concentrations declined in a bi-exponential manner, with a distribution half-life of 
1.75 days and terminal half-life 19.4 days. The systemic clearance was 215 ml/day (range: 69-622 ml/day). 
 
Special patient populations 
 
Paediatric population: The pharmacokinetic parameters are based on individual parameter estimates from a 
population pharmacokinetic analysis of 53 patients from a study in paediatric patients. Following intravenous 
administration of 10 mg/kg on Days 0, 14 and 28, and at 4-week intervals thereafter, belimumab exposures 
were similar between paediatric and adult SLE subjects. Steady-state geometric mean Cmax, Cmin, and 
AUC values were 305 µg/mL, 42 µg/mL, and 2569 day•µg/mL in the 5- to 11-year-old-group, and 
317 µg/mL, 52 µg/mL, and 3126 day•µg/mL in the 12- to 17-year-old-group (n=43). 
 
Elderly: Benlysta has been studied in a limited number of elderly patients. Within the overall SLE 
intravenous study population, age did not affect belimumab exposure in the population pharmacokinetic 
analysis. However, given the small number of subjects ≥65 years, an effect of age cannot be ruled out 
conclusively. 
 
Renal impairment: No specific studies have been conducted to examine the effects of renal impairment on 
the pharmacokinetics of belimumab. During clinical development Benlysta was studied in patients with SLE 
and renal impairment (261 subjects with moderate renal impairment, creatinine clearance ≥30 and 
<60 ml/min; 14 subjects with severe renal impairment, creatinine clearance ≥15 and <30 ml/min). The 
reduction in systemic clearance estimated by population PK modelling for patients at the midpoints of the 
renal impairment categories relative to patients with median creatinine clearance in the PK population 
(79.9 ml/min) were 1.4% for mild (75 ml/min), 11.7% for moderate (45 ml/min) and 24.0% for severe 
(22.5 ml/min) renal impairment. Although proteinuria (≥2 g/day) increased belimumab clearance and 
decreases in creatinine clearance decreased belimumab clearance, these effects were within the expected 
range of variability. Therefore, no dose adjustment is recommended for patients with renal impairment. 
 
Hepatic impairment: No specific studies have been conducted to examine the effects of hepatic impairment 
on the pharmacokinetics of belimumab. IgG1 molecules such as belimumab are catabolised by widely 
distributed proteolytic enzymes, which are not restricted to hepatic tissue and changes in hepatic function are 
unlikely to have any effect on the elimination of belimumab. 
 
Body weight/Body Mass Index (BMI)  
 
Weight-normalised belimumab dosing leads to decreased exposure for underweight subjects (BMI <18.5) 
and to increased exposure for obese subjects (BMI ≥30). BMI-dependent changes in exposure did not lead to 
corresponding changes in efficacy. Increased exposure for obese subjects receiving 10 mg/kg belimumab did 
not lead to an overall increase in AE rates or serious AEs compared to obese subjects receiving placebo. 
However, higher rates of nausea, vomiting and diarrhoea were observed in obese patients. None of these 
gastrointestinal events in obese patients were serious. No dose adjustment is recommended for underweight 
or obese subjects. 
 
Transitioning from intravenous to subcutaneous administration 
 
SLE patients transitioning from 10 mg/kg intravenously every 4 weeks to 200 mg subcutaneously weekly 
using a 1 to 4 week switching interval had pre-dose belimumab serum concentrations at their first 
subcutaneous dose close to their eventual subcutaneous steady-state trough concentration (see section 4.2). 
Based on simulations with population PK parameters the steady-state average belimumab concentrations for 
200 mg subcutaneous every week were similar to 10 mg/kg intravenous every 4 weeks. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on studies of repeated dose toxicity and toxicity 
to reproduction. 



33 

 
Intravenous and subcutaneous administration to monkeys resulted in the expected reduction in the number of 
peripheral and lymphoid tissue B cell counts with no associated toxicological findings. 
 
Reproductive studies have been performed in pregnant cynomolgus monkeys receiving belimumab 
150 mg/kg by intravenous infusion (approximately 9 times the anticipated maximum human clinical 
exposure) every 2 weeks for up to 21 weeks, and belimumab treatment was not associated with direct or 
indirect harmful effects with respect to maternal toxicity, developmental toxicity, or teratogenicity. 
 
Treatment-related findings were limited to the expected reversible reduction of B cells in both dams and 
infants and reversible reduction of IgM in infant monkeys. B cell numbers recovered after the cessation of 
belimumab treatment by about 1 year post-partum in adult monkeys and by 3 months of life in infant 
monkeys; IgM levels in infants exposed to belimumab in utero recovered by 6 months of age. 
 
Effects on male and female fertility in monkeys were assessed in the 6-month repeat dose toxicology studies 
of belimumab at doses up to and including 50 mg/kg. No treatment-related changes were noted in the male 
and female reproductive organs of sexually mature animals. An informal assessment of menstrual cycling in 
females demonstrated no belimumab-related changes. 
 
As belimumab is a monoclonal antibody no genotoxicity studies have been conducted. No carcinogenicity 
studies or fertility studies (male or female) have been performed. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Citric acid monohydrate (E330) 
Sodium citrate (E331) 
Sucrose 
Polysorbate 80 
 
6.2 Incompatibilities 
 
Benlysta is not compatible with 5% glucose. 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in section 
6.6. 
 
6.3 Shelf life 
 
Unopened vials 
5 years. 
 
Reconstituted solution 
After reconstitution with water for injections, the reconstituted solution, if not used immediately, should be 
protected from direct sunlight, and stored refrigerated at 2°C to 8°C. 
 
Reconstituted and diluted solution for infusion 
Solution of Benlysta diluted in sodium chloride 9 mg/ml (0.9%), sodium chloride 4.5 mg/ml (0.45%), or 
Lactated Ringer’s solution for injection may be stored at 2°C to 8°C or room temperature (15°C to 25°C). 
 
The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C to 8°C). 



34 

Do not freeze. 
Store in the original carton in order to protect from light. 
 
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Benlysta 120 mg powder for concentrate for solution for infusion 
 
Type 1 glass vials (5 ml), sealed with a siliconised chlorobutyl rubber stopper and a flip-off aluminum seal 
containing 120 mg of powder. 
 
Pack size: 1 vial 
 
Benlysta 400 mg powder for concentrate for solution for infusion 
 
Type 1 glass vials (20 ml), sealed with a siliconised chlorobutyl rubber stopper and a flip-off aluminum seal 
 
containing 400 mg of powder. 
 
Pack size: 1 vial 
 
6.6 Special precautions for disposal and other handling 
 
Preparation of 120 mg solution for infusion 
 
Reconstitution 
 
Reconstitution and dilution must be carried out under aseptic conditions. 
 
Allow 10 to 15 minutes for the vial to warm to room temperature (15°C to 25°C). 
 
It is recommended that a 21-25 gauge needle be used when piercing the vial stopper for reconstitution and 
dilution. 
 
The 120 mg single-use vial of belimumab is reconstituted with 1.5 ml of water for injections to yield a final 
concentration of 80 mg/ml belimumab. 
 
The stream of water for injections 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 (15°C to 25°C) 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 water has been added, but it may take 
up to 30 minutes.  
 
Protect the reconstituted solution from sunlight. 
 
If a mechanical reconstitution device is used to reconstitute Benlysta it should not exceed 500 rpm and the 
vial should be 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. 
 
After reconstitution, a volume of 1.5 ml (corresponding to 120 mg belimumab) can be withdrawn from each 
vial. 
 



35 

Dilution 
 
The reconstituted medicinal product is diluted to 250 ml with sodium chloride 9 mg/ml (0.9%), sodium 
chloride 4.5 mg/ml (0.45%), or Lactated Ringer’s solution for injection. For patients whose body weight is 
less than or equal to 40 kg, infusion bags with 100 ml of these diluents may be considered providing that the 
resulting belimumab concentration in the infusion bag does not exceed 4 mg/ml. 
 
5% glucose intravenous solutions are incompatible with Benlysta and must not be used. 
 
From a 250 ml (or 100 ml) infusion bag or bottle of sodium chloride 9 mg/ml (0.9%), sodium chloride 4.5 
mg/ml (0.45%), or Lactated Ringer’s solution for injection, withdraw and discard a volume equal to the 
volume of the reconstituted Benlysta solution required for the patient’s dose. Then add the required volume 
of the reconstituted Benlysta solution 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. 
 
Inspect the Benlysta solution visually for particulate matter and discoloration prior to administration. Discard 
the solution if any particulate matter or discoloration is observed. 
 
The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours. 
 
Preparation of 400 mg solution for infusion 
 
Reconstitution 
 
Reconstitution and dilution must be carried out under aseptic conditions. 
 
Allow 10 to 15 minutes for the vial to warm to room temperature (15°C to 25°C). 
 
It is recommended that a 21-25 gauge needle be used when piercing the vial stopper for reconstitution and 
dilution. 
 
The 400 mg single-use vial of belimumab is reconstituted with 4.8 ml of water for injections to yield a final 
concentration of 80 mg/ml belimumab. 
 
The stream of water for injections 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 (15°C to 25°C) 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 water has been added, but it may take 
up to 30 minutes. 
 
Protect the reconstituted solution from sunlight. 
 
If a mechanical reconstitution device is used to reconstitute Benlysta it should not exceed 500 rpm and the 
vial should be swirled for no longer than 30 minutes. 
 
Once reconstitution is complete, the solution should be opalescent and colourless to pale yellow and without 
particles. Small air bubbles, however, are expected and acceptable. 
 
After reconstitution, a volume of 5 ml (corresponding to 400 mg belimumab) can be withdrawn from each 
vial. 
 
Dilution 
 
The reconstituted medicinal product is diluted to 250 ml with sodium chloride 9 mg/ml (0.9%), sodium 
chloride 4.5 mg/ml (0.45%), or Lactated Ringer’s solution for injection. 
 



36 

5% glucose intravenous solutions are incompatible with Benlysta and must not be used. 
 
From a 250 ml infusion bag or bottle of sodium chloride 9 mg/ml (0.9%), sodium chloride 4.5 mg/ml 
(0.45%), or Lactated Ringer’s solution for injection, withdraw and discard a volume equal to the volume of 
the reconstituted Benlysta solution required for the patient’s dose. Then add the required volume of the 
reconstituted Benlysta solution 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. 
 
Inspect the Benlysta solution visually for particulate matter and discoloration prior to administration. Discard 
the solution if any particulate matter or discoloration is observed. 
 
The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours. 
 
Method of administration 
 
Benlysta is infused over a 1 hour period. 
 
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 co-administration of Benlysta with 
other agents. 
 
No incompatibilities between Benlysta and polyvinylchloride or polyolefin bags have been observed. 
 
Disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline (Ireland) Limited 
12 Riverwalk 
Citywest Business Campus 
Dublin 24 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/700/001 1 vial – 120 mg 
EU/1/11/700/002 1 vial – 400 mg 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 13 July 2011 
Date of latest renewal: 18 February 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  

http://www.ema.europa.eu/


37 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURERS RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND 

USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS 
OF THE MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 

SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

 
 



38 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Human Genome Sciences, Inc. 
Belward Large Scale Manufacturing (LSM) Facility 
9911 Belward Campus Drive 
Rockville, MD 20850 
USA 
 
Name and address of the manufacturers responsible for batch release 
 
GlaxoSmithKline Manufacturing S.P.A 
Strada Provinciale Asolana No. 90 
I-43056 San Polo di Torrile, Parma 
Italy 
 
OR 
 
Glaxo Operations UK Ltd 
Harmire Road 
Barnard Castle 
County Durham, DL12 8DT 
United Kingdom 
 
The printed package leaflet of the medicinal product must state the name and address of the manufacturer 
responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2) 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE 

OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities and 
interventions detailed in the agreed RMP presented in Module 1.8.2. of the marketing authorisation and any 
agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
 

• At the request of the European Medicines Agency;  



39 

 
• Whenever the risk management system is modified, especially as the result of new information being 

received that may lead to a significant change to the benefit/risk profile or as the result of an important 
(pharmacovigilance or risk minimisation) milestone being reached. 

 
• Obligation to complete post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 

Description Due date 

The MAH shall also provide a data report on a long-term controlled safety registry 
where all patients are followed for a minimum of 5 years, based on a protocol agreed 
with CHMP. The safety registry will evaluate the incidence of all-cause mortality and 
adverse events of special interest in patients with systemic lupus erythematosus. 
These adverse events of special interest include serious infections (including 
opportunistic infections and PML), selected serious psychiatric events, and 
malignancies (including non-melanoma skin cancer). 
 

28 February 
2026 

 
  



40 

 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

 
  



41 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 
 



42 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON – PRE-FILLED PEN(S) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Benlysta 200 mg solution for injection in pre-filled pen 
 
belimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml pre-filled pen contains 200 mg belimumab 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: arginine hydrochloride, histidine, histidine monohydrochloride, polysorbate 80, sodium 
chloride, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled pen. 
 
1 pre-filled pen. 
4 pre-filled pens. 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use. 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
PRESS HERE TO OPEN 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



43 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/700/003 1 pre-filled pen 
EU/1/11/700/004 4 pre-filled pens 
 
 
13. BATCH NUMBER, DONATION AND PRODUCT CODES 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
benlysta pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN  



44 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER CARTON – Multipack containing 12 pre-filled pens (3 packs of 4 pre-filled pens)-with blue box  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Benlysta 200 mg solution for injection in pre-filled pen 
 
belimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml pre-filled pen contains 200 mg belimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: arginine hydrochloride, histidine, histidine monohydrochloride, polysorbate 80, sodium 
chloride, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled pen. 
 
Multipack:12 pre-filled pens (3 cartons of 4 pre-filled pens). 
Do not sell separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use. 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
 



45 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline (Ireland) Limited  
12 Riverwalk  
Citywest Business Campus  
Dublin 24 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/700/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
benlysta pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN  



46 

 
PARTICULARS TO APPEAR ON INTERMEDIATE PACKAGING 
 
CARTON –- PRE-FILLED PEN- Multipack containing 12 pre-filled pens (3 packs of 4 pre-filled pens)-
with out blue box 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Benlysta 200 mg solution for injection in pre-filled pen  
 
belimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml pre-filled pen contains 200 mg belimumab 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: arginine hydrochloride, histidine, histidine monohydrochloride, polysorbate 80, sodium 
chloride, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled pen. 
 
4 pre-filled pens. Component of a multipack. 
Do not sell separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use. 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



47 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline (Ireland) Limited  
12 Riverwalk 
Citywest Business Campus  
Dublin 24  
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
benlysta pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 



48 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

PRE-FILLED PEN LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Benlysta 200 mg injection  
 
belimumab 
SC 
Subcutaneous 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 
 
 
6. OTHER 
 



49 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON - PRE-FILLED SYRINGE(S) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Benlysta 200 mg solution for injection in pre-filled syringe 
 
belimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml pre-filled syringe contains 200 mg belimumab 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: arginine hydrochloride, histidine, histidine monohydrochloride, polysorbate 80, sodium 
chloride, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe. 
 
1 pre-filled syringe. 
4 pre-filled syringes. 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use. 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
PRESS HERE TO OPEN 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



50 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/700/006 1 pre-filled syringe 
EU/1/11/700/007 4 pre-filled syringes 
 
 
13. BATCH NUMBER, DONATION AND PRODUCT CODES 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
benlysta syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



51 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Benlysta 200 mg  
 
belimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 
 
 
6. OTHER 
 



52 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON-VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Benlysta 120 mg powder for concentrate for solution for infusion 
 
belimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 120 mg belimumab (80 mg/ml after reconstitution) 
 
 
3. LIST OF EXCIPIENTS 
 
Citric acid monohydrate (E330), sodium citrate (E331), sucrose, polysorbate 80 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
1 vial 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
For intravenous infusion after reconstitution and dilution. 
Read the package leaflet before use. 
Intravenous use. 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
 
 



53 

Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/700/001 
 
 
13. BATCH NUMBER, DONATION AND PRODUCT CODES 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
  



54 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Benlysta 120 mg powder for concentrate for solution for infusion 
 
belimumab 
IV 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
120 mg 
 
 
6. OTHER 
 
 



55 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON-VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Benlysta 400 mg powder for concentrate for solution for infusion 
 
belimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 400 mg belimumab (80 mg/ml after reconstitution) 
 
 
3. LIST OF EXCIPIENTS 
 
Citric acid monohydrate (E330), sodium citrate (E331), sucrose, polysorbate 80 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
1 vial 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
For intravenous infusion after reconstitution and dilution. 
Read the package leaflet before use. 
Intravenous use. 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
 
 



56 

Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/700/002 
 
 
13. BATCH NUMBER, DONATION AND PRODUCT CODES 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
  



57 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Benlysta 400 mg powder for concentrate for solution for infusion 
 
belimumab 
IV 
 
 
2. METHOD AND ROUTE OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
400 mg 
 
6. OTHER 
 
 
  



58 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
B. PACKAGE LEAFLET 

 
  



59 

 
Package leaflet: Information for the user 

 
Benlysta 200 mg solution for injection in pre-filled pen 

 
belimumab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how to 
report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor. 
-  This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if 

their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 

leaflet. See section 4. 
 
What is in this leaflet: 
1. What Benlysta is and what it is used for 
2. What you need to know before you use Benlysta 
3. How Benlysta is used 
4. Possible side effects 
5. How to store Benlysta 
6. Contents of the pack and other information 

Step-by-step instructions for using the pre-filled pen 
 
 
1. What Benlysta is and what it is used for 
 
Benlysta as a subcutaneous injection is a medicine used to treat lupus (systemic lupus erythematosus, SLE) 
in adults (18 years of age and older) whose disease is still highly active despite standard treatment. 
 
Lupus is a disease in which the immune system (the system that fights infection) attacks your own cells and 
tissues, causing inflammation and organ damage. It can affect almost any organ in the body, and is thought to 
involve a type of white blood cells called B cells. 
 
Benlysta contains belimumab (a monoclonal antibody). It reduces the number of B cells in your blood by 
blocking the action of BLyS, a protein that helps B cells to live longer and is found in high levels in people 
with lupus. 
 
You will be given Benlysta as well as your usual treatment for lupus. 
 
 
2.  What you need to know before you use Benlysta  
 
Do not use Benlysta 
 
• if you are allergic to belimumab or any of the other ingredients of this medicine (listed in section 6). 

 
 Check with your doctor if this may apply to you. 

 



60 

Warnings and precautions 
Talk to your doctor before you use Benlysta: 
 
• if you have a current or long-term infection or if you often get infections. Your doctor will decide if you 

can be given Benlysta 
• if you are planning to have a vaccination or have had a vaccination within the last 30 days. Some 

vaccines should not be given just before or during treatment with Benlysta 
• if your lupus affects your kidneys or nervous system 
• if you are HIV positive or have low immunoglobulin levels 
• if you have, or have had, hepatitis B or C 
• if you have had an organ transplant, or a bone marrow or stem cell transplant 
• if you have had cancer. 
 

 Tell your doctor if any of these may apply to you. 
 
Depression and suicide 
There have been reports of depression, suicidal thoughts, and suicide attempts including suicide during 
treatment with Benlysta. Tell your doctor if you have a history of these conditions. If you experience new or 
worsening symptoms at any time: 
 

 Contact your doctor or go to a hospital straight away. 
 
If you feel depressed or have thoughts of harming yourself or committing suicide, you may find it helpful to 
tell a relative or close friend and ask them to read this leaflet. You might ask them to tell you if they are 
worried about changes in your mood or behaviour. 
 
Look out for important symptoms 

People taking medicines that affect their immune system may be more at risk of infections, including a rare 
but serious brain infection called progressive multifocal leukoencephalopathy (PML). 

 Read the information ‘Increased risk of brain infection’ in section 4 of this leaflet. 
 
To improve the traceability of this medicine, you and your healthcare provider should record the Benlysta lot 
number. It is recommended that you make a note of this information in case you are asked for it in the future. 
 
Children and adolescents 
Do not give Benlysta as a subcutaneous injection to children or adolescents younger than 18 years of age. 
 
Other medicines and Benlysta 
 
Tell your doctor if you are taking any other medicines, if you have recently taken or might take any other 
medicines. 
 
In particular tell your doctor if you are being treated with medicines that affect your immune system:  
• cyclophosphamide (a medicine to treat some cancers and autoimmune disorders)  
• any medicine that affects your B cells (to treat cancer or inflammatory diseases). 

 
 Tell your doctor. Using such medicines in combination with Benlysta may make your immune 

system less effective. This could increase your risk of a serious infection. 
 
Pregnancy and breast-feeding 
 
Contraception in women of childbearing potential 
 
• Use an effective method of contraception while you are being treated with Benlysta and for at least 4 

months after the last dose. 



61 

 
Pregnancy 
 
Benlysta is not usually recommended if you are pregnant. 
 
• Tell your doctor if you are pregnant, think you may be pregnant, or are planning to have a baby. Your 

doctor will decide if you can use Benlysta. 
• If you become pregnant while being treated with Benlysta, tell your doctor. 
 
Breast-feeding 
 
Tell your doctor if you are breast-feeding. It is likely that Benlysta can pass into breast milk. Your doctor 
will discuss with you whether you should stop treatment with Benlysta while you are breast-feeding, or if 
you should stop breast-feeding. 
 
Driving and using machines 
Benlysta can have side effects which may make you less able to drive or use machines.   
 
Important information about the contents of Benlysta  
This medicine contains less than 1 mmol sodium (23 mg) per dose, so it is essentially ‘sodium-free’. 
 
 
3. How Benlysta is used  
 
How much to use 
 
Adults (18 years of age and older) 
The recommended dose is 200 mg (complete contents of one pen) once a week, injected under your skin on 
the same day each week.  
 
If you wish to change your dosing day: 
Take a dose on the new day (even if it is less than a week since your last dose).  Continue with the new 
weekly schedule from that day. 
 
Injecting Benlysta 
Your doctor or nurse will show you or your caregiver how to inject Benlysta. Your first injection with the 
Benlysta pre-filled pen will be supervised by your doctor or nurse. After you have been trained on how to 
use the pen, your doctor or nurse may decide that you can give yourself the injection, or your caregiver can 
give it to you. Your doctor or nurse will also tell you what signs and symptoms to look out for when using 
Benlysta, because serious allergic reactions can occur (see ‘Allergic reactions’ in section 4). 
 
You inject Benlysta under your skin in your stomach area (abdomen) or upper leg (thigh).  
 
Benlysta subcutaneous injection must not be injected into a vein (intravenously). 
 
Instructions for using the pre-filled pen are given at the end of this leaflet. 
 
If you use more Benlysta than you should 
If this happens, immediately contact your doctor or nurse, who will monitor you for any signs or symptoms 
of side effects, and treat these symptoms if necessary. If possible show them the pack, or this leaflet.  
 
If you forget to use Benlysta 
Inject the missed dose as soon as you remember. Then continue with your normal weekly schedule as usual 
or start a new weekly schedule starting from the day you inject the missed dose.  
If you do not notice that you have missed a dose until it is already time for your next dose, then just inject 
this next dose as planned. It is not necessary to inject two doses on the same day. 



62 

 
Stopping treatment with Benlysta 
Your doctor will decide if you need to stop using Benlysta. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Allergic reactions — get medical help immediately 
Benlysta can cause a reaction to the injection, or an allergic (hypersensitivity) reaction.  
These are common side effects (may affect up to 1 in 10 people).  They can occasionally be severe 
(uncommon, affecting up to 1 in 100 people), and could be life-threatening. These severe reactions are more 
likely to happen on the day of your first or second treatment with Benlysta, but can be delayed and occur 
several days afterwards.  
 
Tell your doctor or nurse immediately, or go to the Emergency department of your nearest hospital, if 
you get any of the following symptoms of an allergic or injection-related reaction:  
• swelling of the face, lips, mouth or tongue 
• wheezing, difficulty in breathing or shortness of breath 
• rash 
• itchy raised bumps or hives. 
 
Rarely, less severe delayed reactions to Benlysta can also occur, usually 5 to 10 days after an injection. 
They include symptoms such as rash, feeling sick, tiredness, muscle aches, headache, or facial swelling.  
If you experience these symptoms, particularly if you get two or more of them together: 

 Tell your doctor or nurse. 
 
Infections 
Benlysta can make you more likely to get infections, including infection of the urinary tract and airways. 
These are very common and may affect more than 1 in 10 people. Some infections can be severe and can 
uncommonly cause death. 
 
If you get any of the following symptoms of an infection: 
• fever and/or chills 
• cough, breathing problems 
• diarrhoea, vomiting 
• burning sensation while passing urine; urinating often 
• warm, red or painful skin or sores on your body. 

 Tell your doctor or nurse immediately. 
 
Depression and suicide 
There have been reports of depression, suicidal thoughts, and suicide attempts during treatment with 
Benlysta. Depression can affect up to 1 in 10 people, suicidal thoughts and suicide attempts can affect up to 
1 in 100 people. If you feel depressed, have thoughts about harming yourself or other distressing thoughts, or 
if you are depressed and notice that you feel worse or develop new symptoms: 
 
 Contact your doctor or go to a hospital straight away. 

 
Increased risk of brain infection 
Medicines that weaken your immune system, such as Benlysta, may put you at higher risk of getting a rare 
but serious and life-threatening brain infection called progressive multifocal leukoencephalopathy (PML). 
 
Symptoms of PML include: 
• memory loss 
• trouble in thinking 



63 

• difficulty with talking or walking 
• loss of vision. 

 Tell your doctor immediately if you have any of these symptoms, or similar problems that have 
lasted over several days. 

 
If you already had these symptoms before you started treatment with Benlysta: 

 Tell your doctor immediately if you notice any changes in these symptoms. 
 
 
Other possible side effects: 
 
Very common side effects 
These may affect more than 1 in 10 people: 
• bacterial infections (see ‘Infections’ above)  
• feeling sick, diarrhoea. 
 
Common side effects 
These may affect up to 1 in 10 people: 
• high temperature or fever  
• low white blood cell count (can be seen in blood tests) 
• nose, throat or stomach infection 
• pain in hands or feet 
• migraine 
• injection site reactions, for example: rash, redness, itching or swelling of the skin where you have 

injected Benlysta. 
 
Uncommon side effects 
These may affect up to 1 in 100 people: 
• itchy, bumpy rash (hives), skin rash. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in 
this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 
By reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store Benlysta 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry 
date refers to the last day of that month. 
 
Store in a refrigerator (2°C to 8°C). 
 
Do not freeze. 
 
Store in the original package in order to protect from light. 
 
A single Benlysta pre-filled pen can be stored at room temperature (up to 25°C) for a maximum of 12 hours 
– as long as it is protected from light. Once removed from the refrigerator, the pen must be used within 12 
hours or discarded. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw 
away medicines you no longer use. These measures will help protect the environment. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


64 

 
 
6. Contents of the pack and other information 
 
What Benlysta contains 
 
The active ingredient is belimumab.  
 
Each 1 ml pre-filled pen contains 200 mg belimumab. 
 
The other ingredients are arginine hydrochloride, histidine, histidine monohydrochloride, polysorbate 80, 
sodium chloride, water for injections.  See ‘Important information about the contents of Benlysta’ in section 
2 for further information. 
 
What Benlysta looks like and contents of the pack 
 
Benlysta is supplied as a 1 ml colourless to slightly yellow solution in a single use pre-filled pen. 
 
Available in packs of 1 or 4 pre-filled pens in each pack and multipacks comprising 12 pre-filled pens 
(3 packs of 4 pre-filled pens). 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
 
GlaxoSmithKline (Ireland) Limited  
12 Riverwalk  
Citywest Business Campus 
Dublin 24 
Ireland 
 
Manufacturer  
 
Glaxo Operations UK Ltd 
Harmire Road 
Barnard Castle 
County Durham, DL12 8DT 
United Kingdom 
 
OR 
 
GlaxoSmithKline Manufacturing S.P.A 
Strada Provinciale Asolana, 90 
43056 San Polo di Torrile 
Parma 
Italy 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 (0) 10 85 52 00 

Luxembourg/Luxemburg 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 52 00 
 

България Magyarország 



65 

ГлаксоСмитКлайн ЕООД 
Teл.: + 359 2 953 10 34 
 

GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 
 
 

Malta 
GlaxoSmithKline (Malta) Limited 
Tel: + 356 21 238131 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)33 2081100 
 

Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel.: + 49 (0)89 36044 8701 
produkt.info@gsk.com 
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

Ελλάδα 
GlaxoSmithKline Μονοπρόσωπη A.E.B.E. 
Τηλ: + 30 210 68 82 100 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 900 202 700 
es-ci@gsk.com 
 

Portugal 
GlaxoSmithKline – Produtos Farmacêuticos, Lda. 
Tel: + 351 21 412 95 00 
FI.PT@gsk.com  
 

France 
Laboratoire GlaxoSmithKline 
Tél.: + 33 (0)1 39 17 84 44 
diam@gsk.com 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 
 

 
Hrvatska 
GlaxoSmithKline d.o.o. 
Tel:+ 385 1 6051 999 
 

 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com 
 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

Italia 
GlaxoSmithKline S.p.A. 

Sverige 
GlaxoSmithKline AB 

tel:++385


66 

Tel: + 39 (0)45 9218 111 Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 

United Kingdom 
GlaxoSmithKline UK Ltd 
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com  
  

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 
 

 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

 

  
  
  
  
  
  
  

 
 
 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
<----------------------------------------------------------------------------------------------------------------------------- 

  

mailto:gskcyprus@gsk.com
mailto:lv-epasts@gsk.com
http://www.ema.europa.eu/


67 

 

Step-by-step instructions for using the pre-filled pen 
 
Once-Weekly 
 
Follow these instructions on how to use the pre-filled pen correctly. Failure to follow these instructions may 
affect proper function of the pre-filled pen. You should also receive training on how to use the pre-filled pen.  
 
Benlysta is for use under the skin only (subcutaneous). 
 
To improve the traceability of this medicine, you and your healthcare provider should record the Benlysta lot 
number. It is recommended that you make a note of this information in case you are asked for it in the future. 
 
Storage 
 
• Keep refrigerated until 30 minutes before use. 
 
• Keep in the carton in order to protect from light. 
 
• Keep out of the sight and reach of children. 
 
• Do not freeze. 
 
• Do not use if left out at room temperature for more than 12 hours. 

 
 

Warnings 
 
• The pre-filled pen should be used only once and then discarded. 

 
• Do not share your Benlysta pre-filled pen with another person. 
 
• Do not shake. 

 
• Do not use if dropped onto a hard surface.  

 
• Do not remove the ring cap until just before the injection. 

 
Benlysta pre-filled pen parts 
 

 

 

Inspection window 

Grey stopper 
Ring cap 

Gold needle guard Expiry date 

Exp: Month – Year 



68 

Supplies you need for the injection 
 

 

 
1. Gather and check supplies 

 
Gather supplies 
 
• Remove one sealed tray containing a pre-filled pen from the refrigerator. 

 
• Find a comfortable, well-lit and clean surface and place the following supplies within reach: 

 
• Benlysta pre-filled pen 

 
• alcohol swab (not included in the pack) 

 
• gauze pad or cotton wool ball (not included in the pack) 

 
• container with a tight-fitting lid for pen disposal (not included in the pack). 

 
 

• Do not perform the injection if you do not have all the supplies listed. 
 

Check the expiry date 
 

• Peel back the film of the tray and remove the pre-filled pen. 
 

• Check the expiry date on the pre-filled pen. (Figure 1) 
 
 
 
 
 
 
 
 
 
 
 

 Benlysta pre-filled pen 

Alcohol swab 
(not included) Gauze pad or cotton wool ball 

(not included) 



69 

Figure 1 

 
 

 
 

Do not use if the expiry date has passed 
 
2. Prepare and inspect the pre-filled pen 
 
Allow to come to room temperature 

 
• Leave the pen at room temperature for 30 minutes. (Figure 2) Injecting cold Benlysta may take longer 

and may be uncomfortable. 
 

Figure 2 

 
 

 
• Do not warm the pen in any other way. For example, do not warm it in a microwave oven, hot water 

or direct sunlight. 
 
• Do not remove the ring cap during this step. 

 
Inspect the Benlysta solution 
 

• Look in the inspection window to check that the Benlysta solution is colourless to slightly yellow in 
colour. (Figure 3) 

 

Figure 3 

 

 

It is normal to see one or more air bubbles in the solution. 

Exp: Month – Year 

Exp: Month – Year 

Wait 30 minutes min 

Benlysta solution 



70 

 
 

• Do not use if the solution looks cloudy, discoloured or has particles. 
 
 
3. Choose and clean the injection site 
 
Choose the injection site 
 

• Choose an injection site (abdomen or thigh) as seen in Figure 4. 
 

Figure 4 

 

 
 

• Do not inject into the exact same site each time. This is to avoid the skin becoming hardened. 
• Do not inject in areas where the skin is tender, bruised, red or hard. 
• Do not inject within 5 cm (2 inches) of the navel (belly button). 

 
Clean the injection site 
 

• Wash your hands. 
 
Clean the injection site by wiping it with an alcohol swab (Figure 5). Allow the skin to air dry.  
 

Figure 5 

 

 
Do not touch this area again before giving the injection. 
 
4. Prepare for the injection 
 
 



71 

 
 Remove the ring cap. 

 
• Do not remove the ring cap until immediately before the injection. 

 
• Remove the ring cap by pulling or twisting it off. The ring cap may be twisted off either clockwise or 

anti-clockwise. (Figure 6) 
 

Figure 6 

 

 
• Do not put the ring cap back onto the pen. 

 
Position the pen 
 

• Hold the pen comfortably so that you can view the inspection window. This is important so that you 
can confirm a complete dose. (Figure 7) 

Figure 7 

 

 
 

• If needed, firm the injection site by pulling or stretching the skin. 
• Position the pen straight over the injection site (at a 90o angle). Make sure the gold needle guard is flat 

on the skin. 
 
 

5. Inject Benlysta 
 
Start the injection 
 

This will insert the needle and start the injection. 
 

• Firmly press the pen all the way down onto the injection site and hold in place. (Figure 8) 
 
 



72 

 

Figure 8 

 
 
You may hear a first “click” at the start of the injection.  You will see the purple indicator start to move 
through the inspection window. (Figure 9) 

Figure 9 

 
 
 
Complete the injection 
 
Continue to hold the pen down until the purple indicator has stopped moving. You may hear a second “click" 
a few seconds before the purple indicator stops moving. (Figure 10) 

 
 
 
 
 
 
 
 
 
 

first “click” 

Purple indicator 



73 

Figure 10 

 
 

• When the injection is complete, lift the pen from the injection site. 
 
6. Dispose and inspect 
 
Dispose of the used pen 
 

• Do not put the ring cap back onto the pen. 
 

• Dispose of the used pen and ring cap in a container with a tight-fitting lid. 
 

• Ask your doctor or pharmacist for instructions on how to properly dispose of a used pen or 
container of used pens. 

 
• Do not recycle or throw the used pen, or container of used pens, in household waste. 

 
Inspect the injection site 
 
There may be a small amount of blood at the injection site.  
 

• If needed, press a cotton ball or gauze pad on the injection site. 
• Do not rub the injection site. 

 
  

The injection may take up to 15 seconds to complete.  
 

second “click” 
Then wait until… 

 

… purple indicator 
stops moving 



74 

 
Package leaflet: Information for the user 

 
Benlysta 200 mg solution for injection in pre-filled syringe 

 
belimumab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how to 
report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you.  
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor. 
-  This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if 

their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 

leaflet. See section 4. 
 
What is in this leaflet: 
1. What Benlysta is and what it is used for 
2. What you need to know before you use Benlysta 
3. How Benlysta is used 
4. Possible side effects 
5. How to store Benlysta 
6. Contents of the pack and other information 

Step-by-step instructions for using the pre-filled syringe 
 
 
1. What Benlysta is and what it is used for 
 
Benlysta as a subcutaneous injection is a medicine used to treat lupus (systemic lupus erythematosus, SLE) 
in adults (18 years of age and older) whose disease is still highly active despite standard treatment. 
 
Lupus is a disease in which the immune system (the system that fights infection) attacks your own cells and 
tissues, causing inflammation and organ damage. It can affect almost any organ in the body, and is thought to 
involve a type of white blood cells called B cells.  
 
Benlysta contains belimumab (a monoclonal antibody). It reduces the number of B cells in your blood by 
blocking the action of BLyS, a protein that helps B cells to live longer and is found in high levels in people 
with lupus. 
 
You will be given Benlysta as well as your usual treatment for lupus. 
 
 
2.  What you need to know before you use Benlysta  
 
Do not use Benlysta 
 
• if you are allergic to belimumab or any of the other ingredients of this medicine (listed in section 6). 

 
 Check with your doctor if this may apply to you. 

 



75 

Warnings and precautions 
Talk to your doctor before you use Benlysta: 
 
• if you have a current or long-term infection or if you often get infections. Your doctor will decide if you 

can be given Benlysta 
• if you are planning to have a vaccination or have had a vaccination within the last 30 days. Some 

vaccines should not be given just before or during treatment with Benlysta 
• if your lupus affects your kidneys or nervous system 
• if you are HIV positive or have low immunoglobulin levels 
• if you have, or have had, hepatitis B or C 
• if you have had an organ transplant, or a bone marrow or stem cell transplant 
• if you have had cancer. 
 

 Tell your doctor if any of these may apply to you 
 
Depression and suicide 
There have been reports of depression, suicidal thoughts, and suicide attempts including suicide during 
treatment with Benlysta. Tell your doctor if you have a history of these conditions. If you experience new or 
worsening symptoms at any time: 
 

 Contact your doctor or go to a hospital straight away. 
 
If you feel depressed or have thoughts of harming yourself or committing suicide, you may find it helpful to 
tell a relative or close friend and ask them to read this leaflet. You might ask them to tell you if they are 
worried about changes in your mood or behaviour. 
 
Look out for important symptoms 

People taking medicines that affect their immune system may be more at risk of infections, including a rare 
but serious brain infection called progressive multifocal leukoencephalopathy (PML). 

 Read the information ‘Increased risk of brain infection’ in section 4 of this leaflet. 
 
To improve the traceability of this medicine, you and your healthcare provider should record the Benlysta lot 
number. It is recommended that you make a note of this information in case you are asked for it in the future. 
 
Children and adolescents 
Do not give Benlysta as a subcutaneous injection to children or adolescents younger than 18 years of age. 
 
Other medicines and Benlysta 
 
Tell your doctor if you are taking any other medicines, if you have recently taken or might take any other 
medicines. 
 
In particular tell your doctor if you are being treated with medicines that affect your immune system:  
• cyclophosphamide (a medicine to treat some cancers and autoimmune disorders)  
• any medicine that affects your B cells (to treat cancer or inflammatory diseases). 

 

 Tell your doctor. Using such medicines in combination with Benlysta may make your immune 
system less effective. This could increase your risk of a serious infection. 

 
Pregnancy and breast-feeding 
 
Contraception in women of childbearing potential 
 
• Use an effective method of contraception while you are being treated with Benlysta and for at least 4 

months after the last dose. 



76 

 
Pregnancy 
 
Benlysta is not usually recommended if you are pregnant. 
 
• Tell your doctor if you are pregnant, think you may be pregnant, or are planning to have a baby. Your 

doctor will decide if you can use Benlysta. 
• If you become pregnant while being treated with Benlysta, tell your doctor. 
 
Breast-feeding 
 
Tell your doctor if you are breast-feeding. It is likely that Benlysta can pass into breast milk. Your doctor 
will discuss with you whether you should stop treatment with Benlysta while you are breast-feeding, or if 
you should stop breast-feeding. 
 
Driving and using machines 
Benlysta can have side effects which may make you less able to drive or use machines.   
 
Important information about the contents of Benlysta  
This medicine contains less than 1 mmol sodium (23 mg) per dose, so it is essentially ‘sodium-free’. 
 
 
3. How Benlysta is used  
 
How much to use 
 
Adults (18 years of age and older) 
The recommended dose is 200 mg (complete contents of one syringe) once a week, injected under your 
skin on the same day each week. 
 
If you wish to change your dosing day: 
Take a dose on the new day (even if it is less than a week since your last dose).  Continue with the new 
weekly schedule from that day. 
 
Injecting Benlysta 
Your doctor or nurse will show you or your caregiver how to inject Benlysta. Your first injection with the 
Benlysta pre-filled syringe will be supervised by your doctor or nurse. After you have been trained on how to 
use the syringe, your doctor or nurse may decide that you can give yourself the injection, or your caregiver 
can give it to you. Your doctor or nurse will also tell you what signs and symptoms to look out for when 
using Benlysta, because serious allergic reactions can occur (see ‘Allergic reactions’ in section 4). 
 
You inject Benlysta under your skin in your stomach area (abdomen) or upper leg (thigh).  
 
Benlysta subcutaneous injection must not be injected into a vein (intravenously). 
 
Instructions for using the pre-filled syringe are given at the end of this leaflet. 
 
If you use more Benlysta than you should 
If this happens, immediately contact your doctor or nurse, who will monitor you for any signs or symptoms 
of side effects, and treat these symptoms if necessary. If possible show them the pack, or this leaflet.  
 
If you forget to use Benlysta 
Inject the missed dose as soon as you remember. Then continue with your normal weekly schedule as usual 
or start a new weekly schedule starting from the day you inject the missed dose.  
If you do not notice that you have missed a dose until it is already time for your next dose, then just inject 
this next dose as planned. It is not necessary to inject two doses on the same day. 



77 

 
Stopping treatment with Benlysta 
Your doctor will decide if you need to stop using Benlysta. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Allergic reactions — get medical help immediately 
Benlysta can cause a reaction to the injection, or an allergic (hypersensitivity) reaction. 
These are common side effects (may affect up to 1 in 10 people).  They can occasionally be severe 
(uncommon, affecting up to 1 in 100 people), and could be life-threatening. These severe reactions are more 
likely to happen on the day of your first or second treatment with Benlysta, but can be delayed and occur 
several days afterwards.  
 
Tell your doctor or nurse immediately, or go to the Emergency department of your nearest hospital, if 
you get any of the following symptoms of an allergic or injection-related reaction:  
• swelling of the face, lips, mouth or tongue 
• wheezing, difficulty in breathing or shortness of breath 
• rash 
• itchy raised bumps or hives. 
 
Rarely, less severe delayed reactions to Benlysta can also occur, usually 5 to 10 days after an injection. 
They include symptoms such as rash, feeling sick, tiredness, muscle aches, headache, or facial swelling.  
If you experience these symptoms, particularly if you get two or more of them together: 
 Tell your doctor or nurse. 

 
Infections 
Benlysta can make you more likely to get infections, including infection of the urinary tract and airways. 
These are very common and may affect more than 1 in 10 people. Some infections can be severe and can 
uncommonly cause death. 
 
If you get any of the following symptoms of an infection: 
• Fever and/or chills 
• cough, breathing problems 
• diarrhoea, vomiting 
• burning sensation while passing urine; urinating often 
• Warm, red or painful skin or sores on your body. 

 Tell your doctor or nurse immediately. 
 
Depression and suicide 
There have been reports of depression, suicidal thoughts, and suicide attempts during treatment with 
Benlysta. Depression can affect up to 1 in 10 people, suicidal thoughts and suicide attempts can affect up to 
1 in 100 people. If you feel depressed, have thoughts about harming yourself or other distressing thoughts, or 
if you are depressed and notice that you feel worse or develop new symptoms: 
 
 Contact your doctor or go to a hospital straight away. 

 
Increased risk of brain infection 
Medicines that weaken your immune system, such as Benlysta, can put you at higher risk of getting a rare 
but serious and life-threatening brain infection called progressive multifocal leukoencephalopathy (PML). 
 
Symptoms of PML include: 
• memory loss 
• trouble in thinking 



78 

• difficulty with talking or walking 
• loss of vision. 

 Tell your doctor immediately if you have any of these symptoms, or similar problems that have 
lasted over several days. 

 
If you already had these symptoms before you started treatment with Benlysta: 

 Tell your doctor immediately if you notice any changes in these symptoms. 
 
 

Other possible side effects: 
 
Very common side effects 
These may affect more than 1 in 10 people: 
• bacterial infections (see ‘Infections’ above)  
• feeling sick, diarrhoea. 
 
Common side effects 
These may affect up to 1 in 10 people: 
• high temperature or fever  
• low white blood cell count (can be seen in blood tests) 
• nose, throat or stomach infection 
• pain in hands or feet 
• migraine 
• injection site reactions, for example: rash, redness, itching or swelling of the skin where you have 

injected Benlysta. 
 
Uncommon side effects 
These may affect up to 1 in 100 people: 
• itchy, bumpy rash (hives), skin rash. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in 
this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 
By reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store Benlysta 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry 
date refers to the last day of that month. 
 
Store in a refrigerator (2°C to 8°C). 
 
Do not freeze. 
 
Store in the original package in order to protect from light. 
 
A single Benlysta pre-filled syringe can be stored at room temperature (up to 25°C) for a maximum of 12 
hours – as long as it is protected from light. Once removed from the refrigerator, the syringe must be used 
within 12 hours or discarded. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw 
away medicines you no longer use. These measures will help protect the environment. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


79 

 
 
6. Contents of the pack and other information 
 
What Benlysta contains 
 
The active ingredient is belimumab.  
 
Each 1 ml pre-filled syringe contains 200 mg belimumab. 
 
The other ingredients are arginine hydrochloride, histidine, histidine monohydrochloride, polysorbate 80, 
sodium chloride, water for injections. See ‘Important information about the contents of Benlysta’ in section 2 
for further information. 
 
What Benlysta looks like and contents of the pack 
 
Benlysta is supplied as a 1 ml colourless to slightly yellow solution in a single use pre-filled syringe with a 
needle cap.  
 
Available in packs of 1 or 4 pre-filled syringes in each pack. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
 
GlaxoSmithKline (Ireland) Limited  
12 Riverwalk  
Citywest Business Campus 
Dublin 24 
Ireland 
 
Manufacturer  
 
Glaxo Operations UK Ltd 
Harmire Road 
Barnard Castle 
County Durham, DL12 8DT 
United Kingdom 
 
OR 
 
GlaxoSmithKline Manufacturing S.P.A 
Strada Provinciale Asolana, 90 
43056 San Polo di Torrile 
Parma 
Italy 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 (0) 10 85 52 00 

Luxembourg/Luxemburg 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 52 00 
 



80 

България 
ГлаксоСмитКлайн ЕООД 
Teл.: + 359 2 953 10 34 
 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 
 

Malta 
GlaxoSmithKline (Malta) Limited 
Tel: + 356 21 238131 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)33 2081100 
 

Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel.: + 49 (0)89 36044 8701 
produkt.info@gsk.com 
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

Ελλάδα 
GlaxoSmithKline Μονοπρόσωπη A.E.B.E. 
Τηλ: + 30 210 68 82 100 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 900 202 700 
es-ci@gsk.com 
 

Portugal 
GlaxoSmithKline – Produtos Farmacêuticos, Lda. 
Tel: + 351 21 412 95 00 
FI.PT@gsk.com  
 

France 
Laboratoire GlaxoSmithKline 
Tél.: + 33 (0)1 39 17 84 44 
diam@gsk.com 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 
 

 
Hrvatska 
GlaxoSmithKline d.o.o. 
Tel:+ 385 1 6051 999 
 

 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com 
 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

Italia 
GlaxoSmithKline S.p.A. 

Sverige 
GlaxoSmithKline AB 

tel:++385


81 

Tel: + 39 (0)45 9218 111 Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 

United Kingdom 
GlaxoSmithKline UK Ltd 
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com  
  

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 
 

 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

 

  
  
  
  
  
  
  

 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
<----------------------------------------------------------------------------------------------------------------------------- 
  

mailto:gskcyprus@gsk.com
mailto:lv-epasts@gsk.com
http://www.ema.europa.eu/


82 

 

Step-by-step instructions for using the pre-filled syringe 
 
Once-Weekly 
 
Follow these instructions on how to use the pre-filled syringe correctly. Failure to follow these instructions 
may affect proper function of the pre-filled syringe. You should also receive training on how to use the pre-
filled syringe.  
 
Benlysta is for use under the skin only (subcutaneous). 
 
To improve the traceability of this medicine, you and your healthcare provider should record the Benlysta lot 
number. It is recommended that you make a note of this information in case you are asked for it in the future. 
 
Storage 
 
• Keep refrigerated until 30 minutes before use. 
 
• Keep in the carton in order to protect from light. 
 
• Keep out of the sight and reach of children. 
 
• Do not freeze. 

 
• Do not use if left out at room temperature for more than 12 hours. 
 
Warnings 
 
• The pre-filled syringe should be used only once and then discarded. 

 
• Do not share your Benlysta pre-filled syringe with another person. 
 
• Do not shake. 

 
• Do not use if dropped onto a hard surface.  

 
• Do not remove the needle cap until just before the injection. 

 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



83 

 
 
Benlysta pre-filled syringe parts 
 
 
 

 

 
 

Supplies you need for the injection 
 

 

Before use 

Needle cap 

Needle 
Body Plunger 

Inspection 
window 

Finger grips 

After use — needle is covered by needle guard 

Needle guard 
activated 

Benlysta pre-filled syringe 

Alcohol swab 
(not included) Gauze pad or cotton 

wool ball 
(not included) 



84 

 
 

1. Gather and check supplies 
 
Gather supplies 
 

• Remove one sealed tray containing a pre-filled syringe from the refrigerator. 
 

• Find a comfortable, well-lit and clean surface and place the following supplies within reach: 
 

• Benlysta pre-filled syringe 
 

• alcohol swab (not included in the pack) 
 

• gauze pad or cotton wool ball (not included in the pack) 
 

• container with a tight-fitting lid for syringe disposal (not included in the pack). 
 
 

• Do not perform the injection if you do not have all the supplies listed. 
 

Check the expiry date 
 

• Peel back the film of the tray and remove the pre-filled syringe by grasping the middle of the body. 
 

• Check the expiry date on the pre-filled syringe. (Figure 1) 
 

Figure 1 

•  
 

• Do not use if the expiry date has passed. 
 
 

2. Prepare and inspect the pre-filled syringe 
 
Allow to come to room temperature 

 
• Leave the syringe at room temperature for 30 minutes. (Figure 2) Injecting cold Benlysta may take 

longer and may be uncomfortable. 
 

Exp: Month – Year 

Exp: Month – Year 



85 

Figure 2 

 
 
 
 

• Do not warm the syringe in any other way. For example, do not warm it in a microwave oven, hot 
water or direct sunlight. 

 
• Do not remove the needle cap during this step. 

 
Inspect the Benlysta solution 
 

• Look in the inspection window to check that the Benlysta solution is colourless to slightly yellow in 
colour. (Figure 3) 

 

Figure 3 
 

 
• Do not use if the solution looks cloudy, discoloured or has particles. 

 
 
3. Choose and clean the injection site 
 
Choose the injection site 
 

• Choose an injection site (abdomen or thigh) as seen in Figure 4. 
 
 

It is normal to see one or more air bubbles in the solution. 
 

 

Wait 30 minutes 
min 

Benlysta solution 



86 

 

Figure 4 

 

 
 
• Do not inject into the exact same site each time. This is to avoid the skin becoming hardened. 
• Do not inject in areas where the skin is tender, bruised, red or hard. 
• Do not inject within 5 cm (2 inches) of the navel (belly button). 
 
Clean the injection site 
 

• Wash your hands. 
• Clean the injection site by wiping it with an alcohol swab (Figure 5). Allow the skin to air dry.  

 
 

Figure 5 

 
• Do not touch this area again before giving the injection. 

 
4. Prepare for the injection 
 

• Do not remove the needle cap until immediately before the injection. 
 
• Hold the prefilled syringe by the body, and with the needle facing away from you. (Figure 6a)  

 
 
 



87 

• Remove the needle cap by pulling it straight off. (Figure 6b) 
 
 

Figure 6 

 
 
 

You may see a drop of liquid at the end of the needle. This is normal. 
 

• Do not let the needle touch any surface. 
 

• Do not expel any air bubbles from the syringe. 
 

• Do not put the needle cap back onto the syringe. 
 

5. Inject Benlysta 
 
Insert the needle 
 

• Hold the syringe in one hand.  
• Use your free hand to gently pinch the skin around the injection site. (Figure 7) 
• Insert the entire needle into the pinched area of the skin at a slight angle (45°), using a dart-like 

motion. 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

a 

b 



88 

Figure 7 

 
 

• After the needle is completely inserted, release the pinched skin. 
 
 
Complete the injection 
 

• Push the plunger all the way down until all of the solution is injected. (Figure 8) 
 

 
 

Figure 8 

 
 
Keeping hold of the syringe, slowly move your thumb back, allowing the plunger to rise up (Figure 9).  
The needle will automatically rise up into the needle guard.  
 
 

Figure 9 
 

 

Push the plunger all 
the way down 

Slowly move your 
thumb back 



89 

 
 
 
 
6. Dispose and inspect 
 
Dispose of the used syringe 
 

• Dispose of the used syringe and needle cap in a container with a tight-fitting lid.    
 

• Ask your doctor or pharmacist for instructions on how to properly dispose of a used syringe or 
container of used syringes. 

• Do not recycle or throw the used syringe, or container of used syringes in household waste. 
 
Inspect the injection site 
 
There may be a small amount of blood at the injection site.  
 

• If needed, press a cotton ball or gauze pad on the injection site. 
• Do not rub the injection site. 

 
 

 

  



90 

Package leaflet: Information for the user 
 

Benlysta 120 mg powder for concentrate for solution for infusion 
Benlysta 400 mg powder for concentrate for solution for infusion 

 
belimumab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how to 
report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains important 

information for you.  
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor. 
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 

leaflet. See section 4. 
 
What is in this leaflet 
1. What Benlysta is and what it is used for 
2. What you need to know before you are given Benlysta 
3. How Benlysta is used 
4. Possible side effects 
5 How to store Benlysta 
6. Contents of the pack and other information 
 
1. What Benlysta is and what it is used for 
 
Benlysta as an infusion is a medicine used to treat lupus (systemic lupus erythematosus, SLE) in adults and 
children (5 years of age and older) whose disease is still highly active despite standard treatment. 
 
Lupus is a disease in which the immune system (the system that fights infection) attacks your own cells and 
tissues, causing inflammation and organ damage. It can affect almost any organ in the body, and is thought to 
involve a type of white blood cells called B cells.  
 
Benlysta contains belimumab (a monoclonal antibody). It reduces the number of B cells in your blood by 
blocking the action of BLyS, a protein that helps B cells to live longer and is found in high levels in people 
with lupus. 
 
You will be given Benlysta as well as your usual treatment for lupus. 
 
2.  What you need to know before you are given Benlysta  
 
Do not receive Benlysta 
 
• if you are allergic to belimumab or any of the other ingredients of this medicine (listed in section 6). 

 

 Check with your doctor if this may apply to you. 
 
Warnings and precautions 
 
Talk to your doctor before you are given Benlysta 
 
• if you have a current or long-term infection or if you often get infections (see section 4). Your doctor 

will decide if you can be given Benlysta 



91 

• if you are planning to have a vaccination or have had a vaccination within the last 30 days. Some 
vaccines should not be given just before or during treatment with Benlysta 

• if your lupus affects your kidneys or nervous system 
• if you are HIV positive or have low immunoglobulin levels 
• if you have, or have had, hepatitis B or C 
• if you have had an organ transplant or a bone marrow or stem cell transplant 
• if you have had cancer. 
 

 Tell your doctor if any of these may apply to you. 
 
Depression and suicide 
There have been reports of depression, suicidal thoughts, and suicide attempts including suicide during 
treatment with Benlysta. Tell your doctor if you have a history of these conditions. If you experience new or 
worsening symptoms at any time: 
 

 Contact your doctor or go to a hospital straight away. 
 
If you feel depressed or have thoughts of harming yourself or committing suicide, you may find it helpful to 
tell a relative or close friend and ask them to read this leaflet. You might ask them to tell you if they are 
worried about changes in your mood or behaviour. 
 
Look out for important symptoms 

People taking medicines that affect their immune system may be more at risk of infections, including a rare 
but serious brain infection called progressive multifocal leukoencephalopathy (PML). 

 Read the information ‘Increased risk of brain infection’ in section 4 of this leaflet. 
 
To improve the traceability of this medicine, your healthcare provider should record the Benlysta lot number 
in your patient file. You may also wish to make a note of this information in case you are asked for it in the 
future. 
 
Children 
 
This medicine is not intended for use in children younger than 5 years of age. 
 
Other medicines and Benlysta 
 
Tell your doctor if you are taking any other medicines, if you have recently taken or might take any other 
medicines. 
 
In particular tell your doctor if you are being treated with medicines that affect your immune system:  
• cyclophosphamide (a medicine to treat some cancers and autoimmune disorders)  
• any medicine that affects your B cells (to treat cancer or inflammatory diseases). 

 

 Tell your doctor. Using such medicines in combination with Benlysta may make your immune 
system less effective. This could increase your risk of a serious infection. 

 
Pregnancy and breast-feeding 
 
Contraception in women of childbearing potential 
 
• Use an effective method of contraception while you are being treated with Benlysta and for at least 4 

months after the last dose. 
 
Pregnancy 



92 

 
Benlysta is not usually recommended if you are pregnant. 
 
• Tell your doctor if you are pregnant, think you may be pregnant, or are planning to have a baby. Your 

doctor will decide if you can be given Benlysta. 
• If you become pregnant while being treated with Benlysta, tell your doctor. 
 
Breast-feeding 
 
Tell your doctor if you are breast-feeding. It is likely that Benlysta can pass into breast milk. Your doctor 
will discuss with you whether you should stop treatment with Benlysta while you are breast-feeding, or if 
you should stop breast-feeding. 
 
Driving and using machines 
Benlysta can have side effects which may make you less able to drive or use machines.   
 
Important information about the contents of Benlysta 
This medicine contains less than 1 mmol sodium (23 mg) per dose, so it is essentially sodium-free. 
 
3. How Benlysta is used  
 
A nurse or doctor will give you Benlysta through a drip in your vein (intravenous infusion) over one hour.   
 
Adults and children (5 years of age and older) 
Your doctor will decide on the correct dose depending on your body weight. The recommended dose is 
10 mg for each kilogram (kg) of your body weight. 
 
You are usually given Benlysta on the first day of treatment then again 14 and 28 days later. After this, 
Benlysta is usually given once every 4 weeks. 
 
Medicine given before an infusion 
Your doctor may decide to give you medicines which help to reduce any infusion reactions before you are 
given Benlysta. These may include a type of medicine called an anti-histamine and a medicine to prevent a 
high temperature. You will be checked closely and if you do have any reactions these will be treated. 
 
Stopping treatment with Benlysta 
Your doctor will decide if you need to stop being given Benlysta. 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Allergic reactions — get medical help immediately 
Benlysta can cause a reaction to the infusion, or an allergic (hypersensitivity) reaction. 
These are common side effects (may affect up to 1 in 10 people).  They can occasionally be severe 
(uncommon, affecting up to 1 in 100 people), and could be life-threatening. These severe reactions are more 
likely to happen on the day of your first or second treatment with Benlysta, but can be delayed and occur 
several days afterwards.  
 
Tell your doctor or nurse immediately, or go to the Emergency department of your nearest hospital, if 
you get any of the following symptoms of an allergic or infusion reaction:  
• swelling of the face, lips, mouth or tongue 
• wheezing, difficulty in breathing or shortness of breath 
• rash 
• itchy raised bumps or hives. 
 



93 

Rarely, less severe delayed reactions to Benlysta can also occur, usually 5 to 10 days after an infusion. 
They include symptoms such as rash, feeling sick, tiredness, muscle aches, headache, or facial swelling.  
If you experience these symptoms, particularly if you get two or more of them together: 

 Tell your doctor or nurse. 
 
Infections 
Benlysta can make you more likely to get infections, including infection of the urinary tract and airways, 
younger children may be at increased risk. These are very common and may affect more than 1 in 10 people. 
Some infections can be severe and can uncommonly cause death. 
 
If you get any of the following symptoms of an infection: 
• Fever and/or chills 
• cough, breathing problems 
• diarrhoea, vomiting 
• burning sensation while passing urine; urinating often 
• warm, red or painful skin or sores on your body. 

 Tell your doctor or nurse immediately. 
 
Depression and suicide 
There have been reports of depression, suicidal thoughts, and suicide attempts during treatment with 
Benlysta. Depression can affect up to 1 in 10 people, suicidal thoughts and suicide attempts can affect up to 
1 in 100 people. If you feel depressed, have thoughts about harming yourself or other distressing thoughts, or 
if you are depressed and notice that you feel worse or develop new symptoms: 
 
 Contact your doctor or go to a hospital straight away. 

 
Increased risk of brain infection 
Medicines that weaken your immune system, such as Benlysta, may put you at higher risk of getting a rare 
but serious and life-threatening brain infection called progressive multifocal leukoencephalopathy (PML). 
 
Symptoms of PML include: 
• memory loss 
• trouble in thinking 
• difficulty with talking or walking 
• loss of vision. 

 Tell your doctor immediately if you have any of these symptoms, or similar problems that have 
lasted over several days. 

 
If you already had these symptoms before you started treatment with Benlysta: 

 Tell your doctor immediately if you notice any changes in these symptoms. 
 
 
Other possible side effects: 
 
Very common side effects 
These may affect more than 1 in 10 people: 
• bacterial infections (see ‘Infections’ above)  
• feeling sick, diarrhoea. 
 
Common side effects 
These may affect up to 1 in 10 people:  
• high temperature or fever 
• low white blood cell count (can be seen in blood tests) 
• nose, throat or stomach infection 
• pain in hands or feet 



94 

• migraine. 
 

Uncommon side effects 
These may affect up to 1 in 100 people: 
• itchy, bumpy rash (hives), skin rash. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in 
this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 
By reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store Benlysta 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry 
date refers to the last day of that month. 
 
Store in a refrigerator (2°C to 8°C). 
 
Do not freeze. 
 
Store in the original package in order to protect from light. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
6. Contents of the pack and other information 
 
What Benlysta contains 
• The active ingredient is belimumab.  

Each 5 ml vial contains 120 mg belimumab. 
  Each 20 ml vial contains 400 mg belimumab. 

After reconstitution, the solution contains 80 mg belimumab per ml. 

• The other ingredients are citric acid monohydrate (E330), sodium citrate (E331), sucrose and 
polysorbate 80. See ‘Important information about the contents of Benlysta’ in section 2 for further 
information. 

 
What Benlysta looks like and contents of the pack 
Benlysta is supplied as a white to off-white powder for solution for infusion, in a glass vial with a siliconised 
rubber stopper and a flip-off aluminium seal. 
 
There is 1 vial in each pack. 
 
Marketing Authorisation Holder  
 
GlaxoSmithKline (Ireland) Limited  
12 Riverwalk  
Citywest Business Campus 
Dublin 24 
Ireland 
 
Manufacturer  
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


95 

GlaxoSmithKline Manufacturing S.P.A. 
Strada Provinciale Asolana No. 90 
I-43056 San Polo di Torrile 
Parma 
Italy 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 (0) 10 85 52 00 

Luxembourg/Luxemburg 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 52 00 
 

България 
ГлаксоСмитКлайн ЕООД 
Teл.: + 359 2 953 10 34 
 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 
 

Malta 
GlaxoSmithKline (Malta) Limited 
Tel: + 356 21 238131 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)33 2081100 
 

Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel.: + 49 (0)89 36044 8701 
produkt.info@gsk.com 
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

Ελλάδα 
GlaxoSmithKline Μονοπρόσωπη A.E.B.E. 
Τηλ: + 30 210 68 82 100 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 900 202 700 
es-ci@gsk.com 
 

Portugal 
GlaxoSmithKline – Produtos Farmacêuticos, Lda. 
Tel: + 351 21 412 95 00 
FI.PT@gsk.com  
 

France 
Laboratoire GlaxoSmithKline 
Tél.: + 33 (0)1 39 17 84 44 
diam@gsk.com 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 
 



96 

 
Hrvatska 
GlaxoSmithKline d.o.o. 
Tel:+ 385 1 6051 999 
 

 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com 
 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

Italia 
GlaxoSmithKline S.p.A. 
Tel: + 39 (0)45 9218 111 

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 

United Kingdom 
GlaxoSmithKline UK Ltd 
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com  
  

 
Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 
 

 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

 

  
  
  
  
  
  
  

 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
<----------------------------------------------------------------------------------------------------------------------------- 
 

tel:++385
mailto:gskcyprus@gsk.com
mailto:lv-epasts@gsk.com
http://www.ema.europa.eu/


97 

The following information is intended for healthcare professionals only: 

 
 
Instructions for use and handling – reconstitution, dilution and administration 

 
In order to improve traceability of biological medicinal products, the tradename and the batch number of the 
administered product should be clearly recorded. 
 
1) How to reconstitute Benlysta 

Reconstitution and dilution needs to be carried out under aseptic conditions. 
 
Allow 10 to 15 minutes for the vial to warm to room temperature (15°C to 25°C). 
 
It is recommended that a 21-25 gauge needle be used when piercing the vial stopper for reconstitution and 
dilution. 
 
WARNING: The 5 ml and 20 ml vials are reconstituted with different volumes of diluent, see below: 
 
120 mg vial 
 
The 120 mg single-use vial of Benlysta is reconstituted with 1.5 ml of water for injections to yield a final 
concentration of 80 mg/ml belimumab.  
 
400 mg vial  
 
The 400 mg single-use vial of Benlysta is reconstituted with 4.8 ml of water for injections to yield a final 
concentration of 80 mg/ml belimumab.  
 
 

Amount of Benlysta Vial size Volume of diluent Final concentration 
 

120 mg 5 ml 1.5 ml 80 mg/ml 
 

400 mg 20 ml 4.8 ml 80 mg/ml 
 

 
The stream of water for injections 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 (15°C to 25°C) 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 water has been added, but it may take 
up to 30 minutes. Protect the reconstituted solution from sunlight.   
 
If a mechanical reconstitution device is used to reconstitute Benlysta it should not exceed 500 rpm and the 
vial should be swirled for no longer than 30 minutes. 
 
2) Before diluting Benlysta 

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. 
 
120 mg vial 

After reconstitution, a volume of 1.5 ml (corresponding to 120 mg belimumab) can be withdrawn from each 
5 ml vial. 

 



98 

400 mg vial 

After reconstitution, a volume of 5 ml (corresponding to 400 mg belimumab) can be withdrawn from each 
20 ml vial. 

 

3) How to dilute the solution for infusion 
The reconstituted medicinal product is diluted to 250 ml with sodium chloride 9 mg/ml (0.9%), sodium 
chloride 4.5 mg/ml (0.45%), or Lactated Ringer’s solution for injection. For patients whose body weight is 
less than or equal to 40 kg, infusion bags with 100 ml of these diluents may be considered providing that the 
resulting belimumab concentration in the infusion bag does not exceed 4 mg/ml. 
 
5% glucose intravenous solutions are incompatible with Benlysta and must not be used.   
 
From a 250 ml (or 100 ml) infusion bag or bottle of sodium chloride 9 mg/ml (0.9%), sodium chloride 4.5 
mg/ml (0.45%), or Lactated Ringer’s solution for injection, withdraw and discard a volume equal to the 
volume of the reconstituted Benlysta solution required for the patient’s dose. Then add the required volume 
of the reconstituted Benlysta solution 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. 

 
Inspect the Benlysta solution visually for particulate matter and discoloration prior to administration. Discard 
the solution if any particulate matter or discoloration is observed. 
 
The reconstituted solution, if not used immediately, should be protected from direct sunlight and stored 
refrigerated at 2°C to 8°C. Solutions diluted in sodium chloride 9 mg/ml (0.9%), sodium chloride 4.5 mg/ml 
(0.45%), or Lactated Ringer’s solution for injection may be stored at 2°C to 8°C or room temperature (15°C 
to 25°C). 
 
The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours. 
 
4) How to administer the diluted solution 

Benlysta is infused over a 1 hour period. 
 
Benlysta should not be infused concomitantly in the same intravenous line with other agents. 
No incompatibilities between Benlysta and polyvinylchloride or polyolefin bags have been observed. 
 
 
 
----------------------------------------------------------------------------------------------------------------------------- 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
{'Title': '1. what benlysta is and what it is used for', 'Section_Content': 'benlysta as a subcutaneous injection is a medicine used to treat lupus (systemic lupus erythematosus, sle) in adults (18 years of age and older) whose disease is still highly active despite standard treatment. lupus is a disease in which the immune system (the system that fights infection) attacks your own cells and tissues, causing inflammation and organ damage. it can affect almost any organ in the body, and is thought to involve a type of white blood cells called b cells. benlysta contains belimumab (a monoclonal antibody). it reduces the number of b cells in your blood by blocking the action of blys, a protein that helps b cells to live longer and is found in high levels in people with lupus. you will be given benlysta as well as your usual treatment for lupus.', 'Entity_Recognition': [{'Text': 'benlysta', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 2, 'BeginOffset': 0, 'EndOffset': 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{'Title': '2. what you need to know before you use benlysta', 'Section_Content': "do not use benlysta if you are allergic to belimumab or any of the other ingredients of this medicine (listed in section 6). check with your doctor if this may apply to you. warnings and precautions talk to your doctor before you use benlysta: if you have a current or long-term infection or if you often get infections. your doctor will decide if you can be given benlysta if you are planning to have a vaccination or have had a vaccination within the last 30 days. some vaccines should not be given just before or during treatment with benlysta if your lupus affects your kidneys or nervous system if you are hiv positive or have low immunoglobulin levels if you have, or have had, hepatitis b or c if you have had an organ transplant, or a bone marrow or stem cell transplant if you have had cancer. tell your doctor if any of these may apply to you. depression and suicide there have been reports of depression, suicidal thoughts, and suicide attempts including suicide during treatment with benlysta. tell your doctor if you have a history of these conditions. if you experience new or worsening symptoms at any time: contact your doctor or go to a hospital straight away. if you feel depressed or have thoughts of harming yourself or committing suicide, you may find it helpful to tell a relative or close friend and ask them to read this leaflet. you might ask them to tell you if they are worried about changes in your mood or behaviour. look out for important symptoms people taking medicines that affect their immune system may be more at risk of infections, including a rare but serious brain infection called progressive multifocal leukoencephalopathy (pml). read the information 'increased risk of brain infection' in section 4 of this leaflet. to improve the traceability of this medicine, you and your healthcare provider should record the benlysta lot number. it is recommended that you make a note of this information in case you are asked for it in the future. children and adolescents do not give benlysta as a subcutaneous injection to children or adolescents younger than 18 years of age. other medicines and benlysta tell your doctor if you are taking any other medicines, if you have recently taken or might take any other medicines. in particular tell your doctor if you are being treated with medicines that affect your immune system: cyclophosphamide (a medicine to treat some cancers and autoimmune disorders) any medicine that affects your b cells (to treat cancer or inflammatory diseases). tell your doctor. using such medicines in combination with benlysta may make your immune system less effective. this could increase your risk of a serious infection. pregnancy and breast-feeding contraception in women of childbearing potential use an effective method of contraception while you are being treated with benlysta and for at least 4 months after the last dose. pregnancy benlysta is not usually recommended if you are pregnant. tell your doctor if you are pregnant, think you may be pregnant, or are planning to have a baby. your doctor will decide if you can use benlysta. if you become pregnant while being treated with benlysta, tell your doctor. breast-feeding tell your doctor if you are breast-feeding. it is likely that benlysta can pass into breast milk. your doctor will discuss with you whether you should stop treatment with benlysta while you are breast-feeding, or if you should stop breast-feeding. driving and using machines benlysta can have side effects which may make you less able to drive or use machines. important information about the contents of benlysta this medicine contains less than 1 mmol sodium (23 mg) per dose, so it is essentially 'sodium-free'.", 'Entity_Recognition': [{'Text': 'benlysta', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 4, 'BeginOffset': 11, 'EndOffset': 19, 'Score': 0.6644383072853088, 'Text': 'benlysta', 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{'Title': '3. how benlysta is used', 'Section_Content': "how much to use adults (18 years of age and older) the recommended dose is 200 mg (complete contents of one pen) once a week, injected under your skin on the same day each week. if you wish to change your dosing day: take a dose on the new day (even if it is less than a week since your last dose). continue with the new weekly schedule from that day. injecting benlysta your doctor or nurse will show you or your caregiver how to inject benlysta. your first injection with the benlysta pre-filled pen will be supervised by your doctor or nurse. after you have been trained on how to use the pen, your doctor or nurse may decide that you can give yourself the injection, or your caregiver can give it to you. your doctor or nurse will also tell you what signs and symptoms to look out for when using benlysta, because serious allergic reactions can occur (see 'allergic reactions' in section 4). you inject benlysta under your skin in your stomach area (abdomen) or upper leg (thigh). benlysta subcutaneous injection must not be injected into a vein (intravenously). instructions for using the pre-filled pen are given at the end of this leaflet. if you use more benlysta than you should if this happens, immediately contact your doctor or nurse, who will monitor you for any signs or symptoms of side effects, and treat these symptoms if necessary. if possible show them the pack, or this leaflet. if you forget to use benlysta inject the missed dose as soon as you remember. then continue with your normal weekly schedule as usual or start a new weekly schedule starting from the day you inject the missed dose. if you do not notice that you have missed a dose until it is already time for your next dose, then just inject this next dose as planned. it is not necessary to inject two doses on the same day. stopping treatment with benlysta your doctor will decide if you need to stop using benlysta.", 'Entity_Recognition': [{'Text': 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{'Title': '4. possible side effects', 'Section_Content': "like all medicines, this medicine can cause side effects, although not everybody gets them. allergic reactions — get medical help immediately benlysta can cause a reaction to the injection, or an allergic (hypersensitivity) reaction. these are common side effects (may affect up to 1 in 10 people). they can occasionally be severe (uncommon, affecting up to 1 in 100 people), and could be life-threatening. these severe reactions are more likely to happen on the day of your first or second treatment with benlysta, but can be delayed and occur several days afterwards. tell your doctor or nurse immediately, or go to the emergency department of your nearest hospital, if you get any of the following symptoms of an allergic or injection-related reaction: swelling of the face, lips, mouth or tongue wheezing, difficulty in breathing or shortness of breath rash itchy raised bumps or hives. rarely, less severe delayed reactions to benlysta can also occur, usually 5 to 10 days after an injection. they include symptoms such as rash, feeling sick, tiredness, muscle aches, headache, or facial swelling. if you experience these symptoms, particularly if you get two or more of them together: tell your doctor or nurse. infections benlysta can make you more likely to get infections, including infection of the urinary tract and airways. these are very common and may affect more than 1 in 10 people. some infections can be severe and can uncommonly cause death. if you get any of the following symptoms of an infection: fever and/or chills cough, breathing problems diarrhoea, vomiting burning sensation while passing urine; urinating often warm, red or painful skin or sores on your body. tell your doctor or nurse immediately. depression and suicide there have been reports of depression, suicidal thoughts, and suicide attempts during treatment with benlysta. depression can affect up to 1 in 10 people, suicidal thoughts and suicide attempts can affect up to 1 in 100 people. if you feel depressed, have thoughts about harming yourself or other distressing thoughts, or if you are depressed and notice that you feel worse or develop new symptoms: contact your doctor or go to a hospital straight away. increased risk of brain infection medicines that weaken your immune system, such as benlysta, may put you at higher risk of getting a rare but serious and life-threatening brain infection called progressive multifocal leukoencephalopathy (pml). symptoms of pml include: memory loss trouble in thinking 63 difficulty with talking or walking loss of vision. tell your doctor immediately if you have any of these symptoms, or similar problems that have lasted over several days. if you already had these symptoms before you started treatment with benlysta: tell your doctor immediately if you notice any changes in these symptoms. other possible side effects: very common side effects these may affect more than 1 in 10 people: bacterial infections (see 'infections' above) feeling sick, diarrhoea. common side effects these may affect up to 1 in 10 people: high temperature or fever low white blood cell count (can be seen in blood tests) nose, throat or stomach infection pain in hands or feet migraine injection site reactions, for example: rash, redness, itching or swelling of the skin where you have injected benlysta. uncommon side effects these may affect up to 1 in 100 people: itchy, bumpy rash (hives), skin rash. reporting of side effects if you get any side effects, talk to your doctor or nurse. this includes any possible side effects not listed in this leaflet. you can also report side effects directly via the national reporting system listed in appendix v. by reporting side effects you can help provide more information on the safety of this medicine.", 'Entity_Recognition': [{'Text': 'benlysta', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'all medicines', 'Type': 'TREATMENT', 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{'Title': '5. how to store benlysta', 'Section_Content': 'keep this medicine out of the sight and reach of children. do not use this medicine after the expiry date which is stated on the label and carton after exp. the expiry date refers to the last day of that month. store in a refrigerator (2 to 8). do not freeze. store in the original package in order to protect from light. a single benlysta pre-filled pen can be stored at room temperature (up to 25) for a maximum of 12 hours as long as it is protected from light. once removed from the refrigerator, the pen must be used within 12 hours or discarded. do not throw away any medicines via wastewater or household waste. ask your pharmacist how to throw away medicines you no longer use. these measures will help protect the environment.', 'Entity_Recognition': [{'Text': 'benlysta', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 70, 'EndOffset': 83}, {'Text': 'a single benlysta pre-filled pen', 'Type': 'TREATMENT', 'BeginOffset': 322, 'EndOffset': 354}, {'Text': '25', 'Type': 'NUMBER', 'BeginOffset': 396, 'EndOffset': 398}, {'Text': '12', 'Type': 'NUMBER', 'BeginOffset': 417, 'EndOffset': 419}, {'Text': 'the pen', 'Type': 'TREATMENT', 'BeginOffset': 501, 'EndOffset': 508}, {'Text': '12', 'Type': 'NUMBER', 'BeginOffset': 529, 'EndOffset': 531}]}
{'Title': '6. contents of the pack and other information step-by-step instructions for using the pre-filled pen', 'Section_Content': "what benlysta contains the active ingredient is belimumab. each 1 ml pre-filled pen contains 200 mg belimumab. the other ingredients are arginine hydrochloride, histidine, histidine monohydrochloride, polysorbate 80, sodium chloride, water for injections. see 'important information about the contents of benlysta' in section 2 for further information. what benlysta looks like and contents of the pack benlysta is supplied as a 1 ml colourless to slightly yellow solution in a single use pre-filled pen. available in packs of 1 or 4 pre-filled pens in each pack and multipacks comprising 12 pre-filled pens (3 packs of 4 pre-filled pens). not all pack sizes may be marketed.", 'Entity_Recognition': [{'Text': 'benlysta', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 5, 'EndOffset': 13, 'Score': 0.25582078099250793, 'Text': 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