are potential risk of lack of This activity is efficacy, rash and considered an additional cardiomyopathy. These pharmacovigilance ongoing safety concerns activity and not an were reported in routine additional risk risk minimisation activities. minimisation activity. Consequently, the RMP has not been amended as requested in the round 1 RMP evaluation and therefore, this recommendation remains. 3. It is recommended that the As noted above, an updated The response has been sponsor submits a more up to EU-RMP is submitted that noted. Of note, the date version of the RMP, has a data lock point of 31 documents provided are alongside with a summary May 2014. inconsistent, and this outlining the differences should be corrected prior A summary of the difference between the currently to approval. relating to the ongoing available RMP and the more up safety concern from the to date version. submitted with the initial application and the updated documents provided as part of this response are summarised (points 4.1 to 4.4) 4.1: Cardiac effects 4.1.1. Bradycardia: One case 4.1.1: Pending (bradycardia) and General of bradycardia was acceptance by the Office disorders and administration reported. of Medicines site conditions (Pyrexia) are Authorisation, this is Case X1: PT bradycardia identified AE s, which are considered acceptable. This event of bradycardia described to occur with a occurred in a patient frequency of uncommon. treated for MMA. The event Consequently, these AEs was considered as not should be listed as important serious by the reporter (no identified risks in the table of value of heart rate ongoing safety concerns. available). The patient recovered the same day. Conclusion: OE considers that this bradycardia is probably due to the patient status (decompensation episode associated with vomiting and pyrexia) and is not related to Carbaglu toxicity. Consequently, this AE will be not listed as important identified risk in the table of ongoing safety concerns.
are potential risk of lack of efficacy, rash and cardiomyopathy. These ongoing safety concerns were reported in routine risk minimisation activities. This activity is considered an additional pharmacovigilance activity and not an additional risk minimisation activity. Consequently, the RMP has not been amended as requested in the round 1 RMP evaluation and therefore, this recommendation remains. 3. It is recommended that the sponsor submits a more up to date version of the RMP, alongside with a summary outlining the differences between the currently available RMP and the more up to date version. As noted above, an updated EU-RMP is submitted that has a data lock point of 31 May 2014. A summary of the difference relating to the ongoing safety concern from the submitted with the initial application and the updated documents provided as part of this response are summarised (points 4.1 to 4.4) The response has been noted. Of note, the documents provided are inconsistent, and this should be corrected prior to approval. 4.1: Cardiac effects (bradycardia) and General disorders and administration site conditions (Pyrexia) are identified AE s, which are described to occur with a frequency of uncommon. Consequently, these AEs should be listed as important identified risks in the table of ongoing safety concerns. 4.1.1. Bradycardia: One case of bradycardia was reported. Case X1: PT bradycardia This event of bradycardia occurred in a patient treated for MMA. The event was considered as not serious by the reporter (no value of heart rate available). The patient recovered the same day. Conclusion: OE considers that this bradycardia is probably due to the patient status (decompensation episode associated with vomiting and pyrexia) and is not related to Carbaglu toxicity. Consequently, this AE will be not listed as important identified risk in the table of ongoing safety concerns. 4.1.1: Pending acceptance by the Office of Medicines Authorisation, this is considered acceptable.