BENLYSTA

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.

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 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. 4). 4). In patients with SLE or active lupus nephritis, 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. In patients with SLE, discontinuation of treatment with Benlysta should be considered if there is no improvement in disease control after 6 months of treatment. In patients with active lupus nephritis, Benlysta should be used in combination with corticosteroids and mycophenolate or cyclophosphamide for induction, or mycophenolate or azathioprine for maintenance.

2). Lupus nephritis If a patient with lupus nephritis is being transitioned from Benlysta intravenous administration to subcutaneous administration, the first dose of 200 mg subcutaneous injection should be administered 1 to 2 weeks after the last intravenous dose.

2). 1). Benlysta should be used with caution in the elderly. 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.

2). Hepatic impairment No specific studies with Benlysta have been conducted in patients with hepatic impairment. 2). Paediatric population SLE 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.

Summary of the safety profile in adults The safety of belimumab in patients with SLE has been evaluated in three pre-registration placebo-controlled intravenous studies and one subsequent regional placebo-controlled intravenous study, one placebo-controlled subcutaneous study, and two post-marketing placebo-controlled intravenous studies; the safety in patients with active lupus nephritis has been evaluated in one placebo-controlled intravenous study.

The data presented in the table below reflect exposure in 674 patients from the three pre-registration clinical studies and 470 patients in the subsequent placebo-controlled study with SLE administered Benlysta intravenously (10 mg/kg over a 1-hour period on Days 0, 14, 28, and then every 28 days for up to 52 weeks), and 556 patients with SLE exposed to Benlysta subcutaneously (200 mg once weekly up to 52 weeks).

The safety data presented include data beyond Week 52 in some patients with SLE. The data reflect additional exposure in 224 patients with active lupus nephritis who received Benlysta intravenously (10 mg/kg for up to 104 weeks). 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 84 % of Benlysta-treated patients and 87 % of placebo-treated patients.

The most frequently reported adverse reaction (≥ 5 % of patients with SLE treated with Benlysta plus standard of care and at a rate ≥ 1 % greater than placebo) was nasopharyngitis. The proportion of patients who discontinued treatment due to adverse reactions was 7 % for Benlysta-treated patients and 8 % for placebo-treated patients.

The most frequently reported adverse reactions (> 5 % of patients with active lupus nephritis treated with Benlysta plus standard of care) were upper respiratory tract infection, urinary tract infection, and herpes zoster. 9 % for placebo-treated patients.

Traceability In order to improve traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded. 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.

1). Caution should be exercised if Benlysta is co- administered with other B cell targeted therapy. Infusion reactions and hypersensitivity Administration of Benlysta may result in hypersensitivity reactions and infusion reactions which can be severe, and fatal.

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.

9 % of adult patients, and included anaphylactic reaction, bradycardia, hypotension, angioedema, and dyspnoea. 8). Patients have been reported to develop symptoms of acute hypersensitivity several hours after the infusion has been administered.

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 should be instructed to seek immediate medical attention if they experience any of these symptoms.

1.