RMP reviewer comment Notwithstanding to the evaluation of the nonclinical and clinical aspects of the Safety Specification (SS), the summary of safety concerns is considered acceptable in the context of this application. It is noted that the PI for injectable Briviact advises of AEs associated with intravenous administration: IV administration was associated with infusion site pain in 2.8% of the patients. The sponsor should provide details, if any, of other reports of adverse events specifically associated with injection of Briviact. Pharmacovigilance plan Proposed pharmacovigilance activities In the EU-RMP, the sponsor proposes routine and additional pharmacovigilance for the identified/potential risks and missing information presented in the Summary of Safety Concerns. Table 28: Proposed pharmacovigilance activities. Safety concern Planned action(s) Important identified risks Suicidality (class label for - Routine pharmacovigilance, with targeted anticonvulsant products) suicidality questionnaire Important potential risks Neutropenia - Routine pharmacovigilance, with targeted using severe blood dyscrasias questionnaire Worsening of seizures (as an - Routine pharmacovigilance, with targeted anticonvulsant product) using drug-induced seizure aggravation questionnaire Abuse potential (as a CNS-active - Routine pharmacovigilance, with targeted product) using drug dependence, abuse, and diversion questionnaire Missing information Data during pregnancy and lactation - Routine pharmacovigilance, with targeted up using pregnancy questionnaire - Participation in and sponsorship of EURAP and North American AED Pregnancy Registry – protocols for EURAP and the AED Registry include activities to follow-up the children ‘possible’ Data in paediatrics (i.e. preterm - Routine pharmacovigilance neonates to children aged 16 years) - Head circumference measurements in all including data on neurodevelopment paediatric studies as per protocol and as agreed in the approved Paediatric Investigation Plan (PIP)
RMP reviewer comment Notwithstanding to the evaluation of the nonclinical and clinical aspects of the Safety Specification (SS), the summary of safety concerns is considered acceptable in the context of this application. It is noted that the PI for injectable Briviact advises of AEs associated with intravenous administration: IV administration was associated with infusion site pain in 2.8% of the patients. The sponsor should provide details, if any, of other reports of adverse events specifically associated with injection of Briviact. Pharmacovigilance plan Proposed pharmacovigilance activities In the EU-RMP, the sponsor proposes routine and additional pharmacovigilance for the identified/potential risks and missing information presented in the Summary of Safety Concerns. Table 28: Proposed pharmacovigilance activities. Safety concern Planned action(s) Important identified risks Suicidality (class label for anticonvulsant products) - Routine pharmacovigilance, with targeted suicidality questionnaire Important potential risks Neutropenia - Routine pharmacovigilance, with targeted using severe blood dyscrasias questionnaire Worsening of seizures (as an anticonvulsant product) - Routine pharmacovigilance, with targeted using drug-induced seizure aggravation questionnaire Abuse potential (as a CNS-active product) - Routine pharmacovigilance, with targeted using drug dependence, abuse, and diversion questionnaire Missing information Data during pregnancy and lactation - Routine pharmacovigilance, with targeted using pregnancy questionnaire - Participation in and sponsorship of EURAP and North American AED Pregnancy Registry – protocols for EURAP and the AED Registry include ‘possible’ activities to follow-up the children Data in paediatrics (i.e. preterm neonates to children aged 16 years) including data on neurodevelopment - Routine pharmacovigilance - Head circumference measurements in all paediatric studies as per protocol and as agreed in the approved Paediatric Investigation Plan (PIP) up
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