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
on a MAOI’. It is recommended that the Delegate considers the adequacy of PI in the context of the information provided for products in the same class. Depression, suicidal ideation and behaviour: the approved PIs for other SNRIs in Australia appear to contain the following additional advice: ‘Prescriptions for (product name) should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.’ It is recommended that the Delegate considers the adequacy of PI in the context of the information provided for products in the same class. Angle closure glaucoma: ‘The pupillary dilation that occurs following use of many antidepressant drugs including FETZIMA® may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.’ The wording is confusing as patent iridectomy is a procedure, not a state or a condition. determination by the Delegate. Summary of recommendations It is considered that the sponsor’s response to the TGA has adequately addressed most of the issues identified in the RMP evaluation report. Outstanding issues are detailed below. Outstanding issues Issues in relation to the RMP Details on the following outstanding issues are provided in 14 above. Recommendation 1: The nonclinical evaluation report has made several recommendations to the safety specification of the RMP. The sponsor should update the RMP documents as recommended.