transaminase is not a potential or identified risk. 4.3: Skin and sub cutaneous 4.3: Two cases of hydrosis 4.3: Pending acceptance tissue disorders (increased were reported in the safety by the Office of Medicines sweating) is a reported AE, database until 31 May 2014: Authorisation, this is which is described to occur considered acceptable. For the first case (case X57) with a frequency of common. according to OE, the Consequently, it is causality is unlikely because recommended that this event the baby presented with be added as important sweating within a warm identified risk in the table of environment (hot weather). ongoing safety concerns. Moreover, the onset was unclear and may have commenced before Carbaglu administration. For the second case (case X67), the patient presented at unspecified date excessive sweating. The reporter causality was not mentioned. Conclusion: review of these two cases, OE considers that there is no potential or identified risk for event hyperhydrosis. 4.4: It appears that is no 4.4: OE has confirmed that 4.4: Pending acceptance data available about the safety there remains no data by the Office of Medicines of the product in patients with available about the safety of Authorisation, this is renal and hepatic insufficiency. the product in patients with considered acceptable. Consequently, it is renal and hepatic recommended that these insufficiency. patients groups be added as To address this, within the missing information in the updated RMP, Section 2.4.3 table of ongoing safety Limitations in respect to concerns. populations typically in clinical development programs has been expanded to include patients with renal or hepatic impairment. Furthermore, this cohort of patients has been included in Table 2-8 within the section Important Missing Information. 5. It is recommended that The sponsor hereby This is considered results of the surveillance confirms that the results of acceptable. the surveillance protocol be
transaminase is not a potential or identified risk. 4.3: Skin and sub cutaneous tissue disorders (increased sweating) is a reported AE, which is described to occur with a frequency of common. Consequently, it is recommended that this event be added as important identified risk in the table of ongoing safety concerns. 4.3: Two cases of hydrosis were reported in the safety database until 31 May 2014: For the first case (case X57) according to OE, the causality is unlikely because the baby presented with sweating within a warm environment (hot weather). Moreover, the onset was unclear and may have commenced before Carbaglu administration. For the second case (case X67), the patient presented at unspecified date excessive sweating. The reporter causality was not mentioned. Conclusion: review of these two cases, OE considers that there is no potential or identified risk for event hyperhydrosis. 4.3: Pending acceptance by the Office of Medicines Authorisation, this is considered acceptable. 4.4: It appears that is no data available about the safety of the product in patients with renal and hepatic insufficiency. Consequently, it is recommended that these patients groups be added as missing information in the table of ongoing safety concerns. 4.4: OE has confirmed that there remains no data available about the safety of the product in patients with renal and hepatic insufficiency. To address this, within the updated RMP, Section 2.4.3 Limitations in respect to populations typically in clinical development programs has been expanded to include patients with renal or hepatic impairment. Furthermore, this cohort of patients has been included in Table 2-8 within the section Important Missing Information. 4.4: Pending acceptance by the Office of Medicines Authorisation, this is considered acceptable. 5. It is recommended that results of the surveillance The sponsor hereby confirms that the results of the surveillance protocol be This is considered acceptable.