Benlysta 120 mg, 400 mg

/ GSK

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. 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 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.
Posology: Premedication including an antihistamine, with or without an antipyretic, may be administered before the infusion of Benlysta.
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.
Elderly: The efficacy and safety of Benlysta in the elderly has not been established. Data on patients ≥ 65 years are limited to <1. 8% of the studied population. Therefore, the use of Benlysta in elderly patients is not recommended unless the benefits are expected to outweigh the risks. In case administration of Benlysta to elderly patients is deemed necessary, dose adjustment is not required.
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.
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.
Paediatric population: The safety and efficacy of Benlysta in children and adolescents (<18 years of age) 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 at the attached doctor’s leaflet.
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.

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.

Hypersensitivity to the active substance or to any of the excipients.

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
– 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. 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 patients, and included anaphylactic reaction, bradycardia, hypotension, angioedema, and dyspnea. Infusion reactions occurred more frequently during the first two infusions and tended to decrease with subsequent infusions. 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. 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 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.
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, including opportunistic infections. Severe infections, including fatal cases, have been reported in SLE patients receiving immunosuppressant therapy, including belimumab. Physicians should exercise
caution when considering the use of Benlysta in patients with severe or chronic infections or a history of recurrent infection. Patients who develop an infection while undergoing treatment with Benlysta should be monitored closely and careful consideration given to interrupting immunosuppressant therapy including belimumab until the infection is resolved. The risk of using Benlysta in patients with active or latent tuberculosis is unknown.
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’.

Very common: Bacterial infections, e.g. bronchitis, urinary tract infection,
diarrhoea, nausea.
Common: Gastroenteritis viral, pharyngitis, nasopharyngitis, viral upper respiratory tract infection, leucopenia, hypersensitivity reactions,
depression, migraine, pain in extremity, infusion-related systemic reactions, pyrexia.
See prescribing information for full details.

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).

Pregnancy: There are a limited amount of data from the use of Benlysta in pregnant women. No formal studies have been conducted. Benlysta should not be used during pregnancy unless the potential benefit justifies the potential risk to the foetus.
Lactation: 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.
See prescribing information for full details.

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.

Storage: Store in a refrigerator (2°C to 8°C). Do not freeze. Store in the original carton in order to protect from light.