Other special population: renal impairment, hepatic impairment, and elderly The available nonclinical data do not indicate any risk associated with use of linagliptin to renal or hepatic function [U10-1492]. Metformin is contraindicated in renal impaired and hepatic insufficient patients [R10-5537]. Because of the metformin component of the fixed dose combination, linagliptin/metformin will be contraindicated in renal impaired and hepatic insufficient patients. Data of the individual compounds do not indicate an increased risk for elderly [U07-1910, U08-1185, R10-5239]. Therefore, no additional nonclinical data for linagliptin/metformin will be obtained. [Part I section 1.1.2 of need for additional non-clinical data if the “Specification product is to be used in special population”] Boehringer Ingelheim proposes to update the Australian Product Information to include insufficiency, acute alcohol “Hepatic intoxication, alcoholism (due to the metformin component)” in the Contraindication section, and a statement in the Dosage and Administration section related to Hepatic impairment. Therefore impaired patients” is not required to be included as an It was noted the sponsor proposes a “hepatic potential risk” in the linagliptin and metformin RMP. precautionary PI statement use of “Important “The 2) Include use with insulin as an area of important missing TRAJENTA DUO in combination with insulin has information not been adequately studied.” It was recommended to the Delegate that The Australian Specific Annex has been amended to include lactic Although the sponsor concludes in the RMP the sponsor: acidosis as an identified safety concern (section 3a). routine risk minimisation activities are sufficient Australian educational programme: Boehringer Ingelheim as part of the Australian education and no risk minimisation plan is needed, they Expand this programme to include the provide details of an educational programme for programme is developing a diabetes CME program which will Important identified risk - lactic include information on Trajenta Duo. Australian healthcare professionals (specialist acidosis, which may occur due to the physicians and general practitioners) in the metformin component of the fixed Australian Specific Annex. dose combination.
Other special population: renal impairment, hepatic impairment, and elderly The available nonclinical data do not indicate any risk associated with use of linagliptin to renal or hepatic function [U10-1492]. Metformin is contraindicated in renal impaired and hepatic insufficient patients [R10-5537]. Because of the metformin component of the fixed dose combination, linagliptin/metformin will be contraindicated in renal impaired and hepatic insufficient patients. Data of the individual compounds do not indicate an increased risk for elderly [U07-1910, U08-1185, R10-5239]. Therefore, no additional nonclinical data for linagliptin/metformin will be obtained. [Part I section 1.1.2 “Specification of need for additional non-clinical data if the product is to be used in special population”] Boehringer Ingelheim proposes to update the Australian Product Information to include “Hepatic insufficiency, acute alcohol intoxication, alcoholism (due to the metformin component)” in the Contraindication section, and a statement in the Dosage and Administration section related to Hepatic impairment. Therefore “hepatic impaired patients” is not required to be included as an “Important potential risk” in the linagliptin and metformin RMP. 2) Include use with insulin as an area of important missing information It was noted the sponsor proposes a precautionary PI statement “The use of TRAJENTA DUO in combination with insulin has not been adequately studied.” It was recommended to the Delegate that the sponsor: Australian educational programme: Expand this programme to include the Important identified risk - lactic acidosis, which may occur due to the metformin component of the fixed dose combination. The Australian Specific Annex has been amended to include lactic acidosis as an identified safety concern (section 3a). Boehringer Ingelheim as part of the Australian education programme is developing a diabetes CME program which will include information on Trajenta Duo. Although the sponsor concludes in the RMP routine risk minimisation activities are sufficient and no risk minimisation plan is needed, they provide details of an educational programme for Australian healthcare professionals (specialist physicians and general practitioners) in the Australian Specific Annex.
auspar-linagliptin-metformin-130926.docx