reactions are presented together for the two products. 9. Liver enzyme elevation The recommendations for The evaluator has and hyper bilirubinaemia liver function monitoring in noted that the is an identified risk for the proposed Australian PI sponsor has both Vargatef and Ofev. are identical to the text updated the The product label approved by the EMA for Ofev Australian PI to approved by the US FDA (nintedanib in IPF). align with the for Ofev contains the relevant parts of Hepatic transaminase and following detailed the EU Summary bilirubin levels should be instruction on liver of Product investigated before the function monitoring: Characteristics initiation of treatment with liver function (SmPC). In regard ‘Conduct nintedanib, as a baseline tests (ALT, AST, and to the routine reference. The sponsor bilirubin) prior to risk proposes that start of treatment with Ofev, minimisation, the treatment, liver enzymes and monthly for 3 months, and updated PI is bilirubin should be measured considered every 3 months thereafter, periodically, for example at and as clinically indicated. acceptable. each patient visit, which could Dosage modifications or be at the patient’s IPF interruption may be specialist or family physician, necessary for liver enzyme or as clinically indicated. elevations.’ The sponsor anticipates that In comparison, the patients will be followed up proposed Australian PI by their physician more provides a more general frequently during the first advice on the frequency of weeks/months after monitoring as follows: treatment with nintedanib, transaminase and ‘Hepatic according to routine practice bilirubin levels should be following initiation of a new investigated before the treatment. As the risk of liver initiation of treatment with enzyme elevations is higher in Ofev/Vargatef and these first months, the periodically thereafter (for sponsor considers the example at each patient proposed text in the ASA to be visit) or as clinically appropriate. indicated.’ Compared to the more It is recommended that detailed recommendation the Delegate considers this requested by the FDA, the instruction in the context proposed flexible monitoring of improvement of the recommendations in the safety. Australian PI allow the prescribing physicians to provide personalised liver monitoring frequency according to the patient’s medical history, condition, changes in concomitant therapy and so on.
reactions are presented together for the two products. 9. Liver enzyme elevation and hyper bilirubinaemia is an identified risk for both Vargatef and Ofev. The product label approved by the US FDA for Ofev contains the following detailed instruction on liver function monitoring: ‘Conduct liver function tests (ALT, AST, and bilirubin) prior to treatment with Ofev, monthly for 3 months, and every 3 months thereafter, and as clinically indicated. Dosage modifications or interruption may be necessary for liver enzyme elevations.’ In comparison, the proposed Australian PI provides a more general advice on the frequency of monitoring as follows: ‘Hepatic transaminase and bilirubin levels should be investigated before the initiation of treatment with Ofev/Vargatef and periodically thereafter (for example at each patient visit) or as clinically indicated.’ It is recommended that the Delegate considers this instruction in the context of improvement of the safety. The recommendations for liver function monitoring in the proposed Australian PI are identical to the text approved by the EMA for Ofev (nintedanib in IPF). Hepatic transaminase and bilirubin levels should be investigated before the initiation of treatment with nintedanib, as a baseline reference. The sponsor proposes that start of treatment, liver enzymes and bilirubin should be measured periodically, for example at each patient visit, which could be at the patient’s IPF specialist or family physician, or as clinically indicated. The sponsor anticipates that patients will be followed up by their physician more frequently during the first weeks/months after treatment with nintedanib, according to routine practice following initiation of a new treatment. As the risk of liver enzyme elevations is higher in these first months, the sponsor considers the proposed text in the ASA to be appropriate. Compared to the more detailed recommendation requested by the FDA, the proposed flexible monitoring recommendations in the Australian PI allow the prescribing physicians to provide personalised liver monitoring frequency according to the patient’s medical history, condition, changes in concomitant therapy and so on. The evaluator has noted that the sponsor has updated the Australian PI to align with the relevant parts of the EU Summary of Product Characteristics (SmPC). In regard to the routine risk minimisation, the updated PI is considered acceptable.
auspar-nintedanib-esilate-160208.docx