BENLYSTA

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.

4). A patient may self-inject, or the patient caregiver may administer Benlysta after the healthcare professional determines that it is appropriate. Posology SLE The recommended dose is 200 mg once weekly, administered subcutaneously.

2). 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. Lupus nephritis In patients initiating therapy with Benlysta for active lupus nephritis, the recommended dosage regimen is a 400 mg dose (two 200 mg injections) once weekly for 4 doses, then 200 mg once weekly thereafter.

In patients continuing therapy with Benlysta for active lupus nephritis, the recommended dosage is 200 mg once weekly. Benlysta should be used in combination with corticosteroids and mycophenolate or cyclophosphamide for induction, or mycophenolate or azathioprine for maintenance.

The patient’s condition should be evaluated continuously. Missed doses 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.

Changing the weekly dosing 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.

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.

Summary of the safety profile 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 with SLE from the three pre-registration clinical studies and 470 patients in the subsequent placebo- controlled study 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. Benlysta has not been studied in the following patient groups and is not recommended in: • severe active central nervous system lupus • 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. Hypersensitivity Administration of subcutaneous or intravenous Benlysta may result in hypersensitivity reactions which can be severe, and fatal.

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.

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.

4). Infections The mechanism of action of belimumab could increase the risk for the development of infections, including opportunistic infections. g. 8). Pneumococcal vaccination should be considered before initiating Benlysta treatment.

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