Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
Infections (including upper respiratory tract infections), pruritus, rash, arthralgia, and diarrhoea were the most common adverse reactions , occurring in > 20% of siltuximab-treated patients in Castleman’s disease (CD) clinical studies. The most serious adverse reaction associated with the use of siltuximab was anaphylactic reaction.

Data from all patients treated with siltuximab monotherapy (n = 370) form the overall basis of the safety evaluation.
Table 2 reflects the frequencies of identified adverse reactions in the 87 MCD patients (Study 1, Study 2 and Study 3) treated at the recommended dosage of 11 mg/kg every 3 weeks (details provided in section 5.1).
Tabulated list of adverse reactions
Table 2 lists adverse reactions observed in MCD patients treated with siltuximab at the recommended dosage of 11 mg/kg every 3 weeks. Within the system organ class, adverse reactions are listed under headings of frequency using the following categories: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥1/1000 and <1/100); rare (≥1/10000 and <1/1000); very rare (<1/10000).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 2:     Adverse reactions in siltuximab treated patients in MCD clinical studiesa System organ class                                Adverse reaction
Frequency
Infections and infestations very common                                       Upper respiratory tract infection, urinary tract infection, nasopharyngitis
Blood and lymphatic system disorders very common                                       Neutropenia, thrombocytopenia Immune system disorders common                                            Anaphylactic reaction Metabolism and nutrition disorders very common                                       Hypertriglyceridaemia, hyperuricaemia common                                            Hypercholesterolaemia Nervous system disorders very common                                       Dizziness, headache Respiratory, thoracic and mediastinal disorders very common                                       Oropharyngeal pain
Vascular disorders very common                                       Hypertension
Gastointestinal disorders very common                                       Nausea, abdominal pain, vomiting, constipation, diarrhoea, gastroesophageal reflux disease,
mouth ulceration
Skin and subcutaneous tissue disorders very common                                       Rash, pruritus, eczema Musculoskeletal and connective tissue disorders very common                                       Arthralgia, pain in extremity Renal and urinary disorders very common                                       Renal impairment
General disorders and administration site conditions very common                                       Localised oedema
Investigations very common                                       Weight increased a
All patients with CD treated with siltuximab at recommended dose of 11 mg/kg every 3 weeks [including crossover patients (N = 87)]

Infusion related reactions and hypersensitivity
In clinical studies, siltuximab was associated with an infusion related reaction or hypersensitivity reaction in 5.1% (severe reaction in 0.8%) of patients treated with siltuximab monotherapy.

In long-term treatment of MCD patients with siltuximab at the recommended dosage of 11 mg/kg every 3 weeks, infusion related reactions or hypersensitivity reactions occurred at a frequency of 6.3% (1.3% for severe reactions).

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. Any suspected adverse reactions should be reported to the Ministry of Health, according to the National Regulation by using an online form https://sideeffects.health.gov.il/