Suicidal ideation and behaviours; serotonin behaviours; syndrome and seizures. Serotonin syndrome; Seizures. 5. Long-term use is listed as The sponsor’s Like most newly approved missing information. As a drugs, safety data for 1 year response is proportion of patients with have been provided for satisfactory. The major depression require evaluation of Fetzima. Since sponsor should update long-term treatment, the the AUS-RMP to the product launch in sponsor should provide December 2013, no safety include this specific justification as to why concern regarding the safety analysis. enhanced surveillance is not use (greater than 1 year) required to monitor the was brought to the attention safety of long-term use of of MAH. levomilnacipran. Enhanced surveillance is usually put in place at the beginning of the marketing (from 6 to 12 months after the marketing authorisation). Long-term use is currently considered as missing information in the RMP, and the MAH proposes to perform a specific safety analysis in patients treated with levomilnacipran for more than 1 year in the future Periodic Benefit-Risk Evaluation Reports (PBRERs). 6. In regard to the proposed a. The Product Information of The sponsor’s routine risk minimisation Fetzima will be updated response is activities, the following accordingly. satisfactory. However, recommendations are made the evaluator has b. The Product Information of with regard to the noted that the advice Fetzima will be updated product information on angle closure has accordingly. document: been deleted from the c. The Product Information of updated PI. It is Co-administration with MAO Fetzima will be updated recommended that the inhibitors: the approved PIs accordingly. advice is reinstated as for other SNRIs in Australia follows: appear to contain the following additional pupillary dilation ‘The information: of serious that occurs following ‘Cases reactions, such as potentially use of many life threatening serotonin antidepressant drugs syndrome (characterised by including Fetzima may neuromuscular excitation, trigger acute angle altered mental status and closure glaucoma in a autonomic dysfunction) have patient with been reported in patients anatomically narrow receiving an SNRI in angles who has not had combination with MAOIs and a patent iridectomy.’ RIMA, and in patients who The other PI have recently discontinued an recommendations SNRI and have been started remain for the final
Suicidal ideation and behaviours; Serotonin syndrome; Seizures. behaviours; serotonin syndrome and seizures. 5. Long-term use is listed as missing information. As a proportion of patients with major depression require long-term treatment, the sponsor should provide justification as to why enhanced surveillance is not required to monitor the safety of long-term use of levomilnacipran. Like most newly approved drugs, safety data for 1 year have been provided for evaluation of Fetzima. Since the product launch in December 2013, no safety concern regarding the use (greater than 1 year) was brought to the attention of MAH. Enhanced surveillance is usually put in place at the beginning of the marketing (from 6 to 12 months after the marketing authorisation). Long-term use is currently considered as missing information in the RMP, and the MAH proposes to perform a specific safety analysis in patients treated with levomilnacipran for more than 1 year in the future Periodic Benefit-Risk Evaluation Reports (PBRERs). The sponsor’s response is satisfactory. The sponsor should update the AUS-RMP to include this specific safety analysis. 6. In regard to the proposed routine risk minimisation activities, the following recommendations are made with regard to the product information document: Co-administration with MAO inhibitors: the approved PIs for other SNRIs in Australia appear to contain the following additional information: ‘Cases of serious reactions, such as potentially life threatening serotonin syndrome (characterised by neuromuscular excitation, altered mental status and autonomic dysfunction) have been reported in patients receiving an SNRI in combination with MAOIs and RIMA, and in patients who have recently discontinued an SNRI and have been started a. The Product Information of Fetzima will be updated accordingly. b. The Product Information of Fetzima will be updated accordingly. c. The Product Information of Fetzima will be updated accordingly. The sponsor’s response is satisfactory. However, the evaluator has noted that the advice on angle closure has been deleted from the updated PI. It is recommended that the advice is reinstated as follows: ‘The pupillary dilation that occurs following use of many antidepressant drugs including Fetzima may trigger acute angle closure glaucoma in a patient with anatomically narrow angles who has not had a patent iridectomy.’ The other PI recommendations remain for the final
auspar-levomilnacipran-161213.docx