Opportunistic infection Infusion-related reaction Hyperglycaemia Stevens-Johnson syndrome/Toxic epidermal necrolysis Tumour syndrome Anti-therapeutic antibodies Important potential risks Pancreatitis acute Hepatotoxicity Pulmonary toxicity Reproductive toxicity Thymus depletion (paediatric) Infection with drugs modifying CYP3A4 activity Missing information Safety in paediatrics Safety in the elderly Safety in patients with hepatic, cardiac or renal impairment Long term safety Comment: The Summary of Safety Concerns is unchanged in PSUR 6 as complications’ was ‘GI recognised as a new important potential risk during the reporting period. Safety issues with the potential for major regulatory impact Comment: Information regarding the safety issues described below is collated from the PSURs. In general, the signal evaluation is presented in the PSUR as an overview of the condition followed by a description of the findings in the Phase II Studies’. ‘Pivotal For new signals, a more comprehensive cumulative review may also have been performed. PSUR 5 provides a summary table of numbers up to data lock point for that update, as sourced from the clinical trials programme and from post-marketing sources. The safety findings of the Phase III study, SGN35-005 (described in the efficacy and safety sections above) have not been included in the updates in the PSUR 5, although a study synopsis is provided elsewhere in the PSUR. Two new safety concerns were addressed in PSUR 6: gastrointestinal complications and posterior reversible encephalopathy syndrome (PRES). These have been included below. Notes are made where information related to the risk have been included in the European SmPC to be consistent with the terminology used in the PSURs. This information in general is also included in the Australian version of the SmPC (the Product Information). Neurological toxicity Peripheral neuropathy Peripheral neuropathy is a relatively common dose-limiting toxicity of brentuximab vedotin and is discussed at length in several of the PSURs, most recently in PSUR 5. Peripheral neuropathy, including peripheral sensory neuropathy and peripheral motor neuropathy, emerged as a clinically important neuromuscular AE early in the clinical program of brentuximab vedotin. It ranged from mild distal paraesthesia, affecting fingers and
Opportunistic infection Infusion-related reaction Hyperglycaemia Stevens-Johnson syndrome/Toxic epidermal necrolysis Tumour syndrome Anti-therapeutic antibodies Important potential risks Pancreatitis acute Hepatotoxicity Pulmonary toxicity Reproductive toxicity Thymus depletion (paediatric) Infection with drugs modifying CYP3A4 activity Missing information Safety in paediatrics Safety in the elderly Safety in patients with hepatic, cardiac or renal impairment Long term safety Comment: The Summary of Safety Concerns is unchanged in PSUR 6 as ‘GI complications’ was recognised as a new important potential risk during the reporting period. Safety issues with the potential for major regulatory impact Comment: Information regarding the safety issues described below is collated from the PSURs. In general, the signal evaluation is presented in the PSUR as an overview of the condition followed by a description of the findings in the ‘Pivotal Phase II Studies’. For new signals, a more comprehensive cumulative review may also have been performed. PSUR 5 provides a summary table of numbers up to data lock point for that update, as sourced from the clinical trials programme and from post-marketing sources. The safety findings of the Phase III study, SGN35-005 (described in the efficacy and safety sections above) have not been included in the updates in the PSUR 5, although a study synopsis is provided elsewhere in the PSUR. Two new safety concerns were addressed in PSUR 6: gastrointestinal complications and posterior reversible encephalopathy syndrome (PRES). These have been included below. Notes are made where information related to the risk have been included in the European SmPC to be consistent with the terminology used in the PSURs. This information in general is also included in the Australian version of the SmPC (the Product Information). Neurological toxicity Peripheral neuropathy Peripheral neuropathy is a relatively common dose-limiting toxicity of brentuximab vedotin and is discussed at length in several of the PSURs, most recently in PSUR 5. Peripheral neuropathy, including peripheral sensory neuropathy and peripheral motor neuropathy, emerged as a clinically important neuromuscular AE early in the clinical program of brentuximab vedotin. It ranged from mild distal paraesthesia, affecting fingers and
auspar-brentuximab-vedotin-170914-cer.docx