Benlysta斑麗達

Benlysta Adverse Reactions

belimumab

Manufacturer:

GlaxoSmithKline

Distributor:

Zuellig
/
Agencia Lei Va Hong
Full Prescribing Info
Adverse Reactions
Summary of the safety profile in adults: Powder for concentrate for solution for infusion 120 mg: The safety of belimumab in patients with SLE has been evaluated in 3 placebo-controlled studies. The data described as follows reflect exposure to Benlysta 10 mg/kg in 674 patients with SLE, including 472 exposed for at least 52 weeks. The safety data presented include data beyond Week 52 in some patients. Data from postmarketing reports are also included.
Patients received Benlysta 10 mg/kg intravenously over a 1-hour period on Days 0, 14, 28, and then every 28 days for 52 weeks.
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 93% of Benlysta-treated patients and 92% of placebo-treated patients. The most frequently reported adverse reactions (≥10% of patient with SLE treated with Benlysta plus standard of care and at a rate ≥1% greater than placebo) were nausea, diarrhoea, and pyrexia. The proportion of patients who discontinued treatment due to adverse reactions was 7% for both Benlysta-treated and placebo-treated patients.
Powder for concentrate for solution for infusion 400 mg & Solution for injection: 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 following table 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: Powder for concentrate for solution for infusion 120 mg: Adverse reactions are listed as follows 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. (See Table 7.)

Click on icon to see table/diagram/image

Powder for concentrate for solution for infusion 400 mg & Solution for injection: Adverse reactions are listed as follows 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. (See Table 8.)

Click on icon to see table/diagram/image

Description of selected adverse reactions: Powder for concentrate for solution for infusion 120 mg: Infusion reactions and hypersensitivity: The incidence of infusion reactions and hypersensitivity reactions occurring during or on the same day as an infusion was 17% in the group receiving Benlysta and 15% in the group receiving placebo, with 1% and 0.3%, respectively, requiring permanent treatment discontinuation. These reactions were generally observed on the day of infusion, but acute hypersensitivity reactions may also occur on the day after dosing. Patients with a history of multiple drug allergies or significant hypersensitivity reactions may be at increased risk.
Infections: The overall incidence of infections was 70% in the group receiving Benlysta and 67% in the group receiving placebo. Infections occurring in at least 3% of Benlysta patients and at least 1% more frequently than patients receiving placebo were nasopharyngitis, bronchitis, pharyngitis, cystitis, and gastroenteritis viral. Serious infections occurred in 5% of patients receiving Benlysta or placebo. Infections leading to discontinuation of treatment occurred in 0.6% of patients receiving Benlysta and 1% of patients receiving placebo. Opportunistic infections have been reported in patients treated with Benlysta. Some infections were severe or fatal.
Leucopenia: The incidence of leucopenia reported as an adverse event was 4% in the group receiving Benlysta and 2% in the group receiving placebo.
Psychiatric disorders: Insomnia occurred in 7% of the group receiving Benlysta and 5% of the group receiving placebo. Depression was reported in 5% and 4% of the groups receiving Benlysta and placebo, respectively.
Gastrointestinal disorders: Obese patients [Body mass index (BMI) >30 kg/m2] treated with 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.
Powder for concentrate for solution for infusion 400 mg: Data presented as follows are pooled from the intravenous clinical studies (10 mg/kg intravenous dose only) and the subcutaneous clinical study. Psychiatric disorders also includes 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 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 as follows.
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 randomised, double-blind, placebo-controlled, post-marketing study with Benlysta 10 mg/kg administered intravenously, 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.
Solution for injection: Data presented as follows are pooled from the intravenous clinical studies (10 mg/kg intravenous dose only) and the subcutaneous clinical study. Psychiatric disorders also includes 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 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.
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 1mg/kg Benlysta).
In a randomised, double-blind, placebo-controlled, post-marketing study with Benlysta 10 mg/kg administered intravenously, 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.
Injection site reactions: In the subcutaneous trial, 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.
Paediatric population: Powder for concentrate for solution for infusion 400 mg: 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 Precautions).
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: Powder for concentrate for solution for infusion: 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.
Exclusive offer for doctors
Register for a MIMS account and receive free medical publications worth $768 a year.
Sign up for free
Already a member? Sign in