For the important identified moderate risk: and the to severe hepatic ‘Hepatotoxicity’ missing information: impairment are with hepatic not currently ‘Patients impairment’, the Dosage and available, and Administration section of the therefore, agrees Australian PI states: that ceritinib ‘Caution should be used in patients should not be with severe renal impairment recommended in as there is no experience with patients with ZYKADIA in this population moderate to severe (see Pharmacokinetics; hepatic Special Populations)’. impairment. The However this internal cross Australian PI reference states: ‘The Dosage and pharmacokinetics of ceritinib Administration has not been studied in section [module patients with moderate to 1.3.1.2], severe hepatic impairment. A Precautions section recommended dose has not [module 1.3.1.2] been determined for patients and with moderate to severe hepatic impairment’. section [module Consequently the cautionary 1.3.1.2] have been statement should be amended amended to align to: is not ‘Ceritinib with the EU SmPC recommended for patients language’. with moderate to severe or words The sponsor hepatic impairment’ to that effect. This would states: ‘Novartis ensure internal consistency agrees to include in within the Australian PI, the DOSAGE AND align with the approved EU ADMINISTRATION SmPC and enhance the safe section of the use of this medicine. Australian PI For the important potential [module 1.3.1.2] risk: use of ‘Concomitant the additional ceritinib and strong CYP3A information inhibitors or strong CYP3A regarding strong inducers’, the Dosage and CYP3A inhibitors’. Administration section of the The sponsor Australian PI may be states: ‘The amended as follows: ‘Avoid applicant concurrent use of strong acknowledged that CYP3A inhibitors during data regarding the treatment with ZYKADIA (see potential Interactions with other interaction of Medicines). If concomitant ceritinib with use of a strong CYP3A inhibitor is unavoidable, pump inhibitors reduce the ZYKADIA dose by are not currently approximately one-third, available and rounded to the nearest therefore agrees to multiple of the 150 mg add this dosage strength. Patients information in the should be carefully
For the important identified risk: ‘Hepatotoxicity’ and the missing information: ‘Patients with hepatic impairment’, the Dosage and Administration section of the Australian PI states: ‘Caution should be used in patients with severe renal impairment as there is no experience with ZYKADIA in this population (see Pharmacokinetics; Special Populations)’. However this internal cross reference states: ‘The pharmacokinetics of ceritinib has not been studied in patients with moderate to severe hepatic impairment. A recommended dose has not been determined for patients with moderate to severe hepatic impairment’. Consequently the cautionary statement should be amended to: ‘Ceritinib is not recommended for patients with moderate to severe hepatic impairment’ or words to that effect. This would ensure internal consistency within the Australian PI, align with the approved EU SmPC and enhance the safe use of this medicine. For the important potential risk: ‘Concomitant use of ceritinib and strong CYP3A inhibitors or strong CYP3A inducers’, the Dosage and Administration section of the Australian PI may be amended as follows: ‘Avoid concurrent use of strong CYP3A inhibitors during treatment with ZYKADIA (see Interactions with other Medicines). If concomitant use of a strong CYP3A inhibitor is unavoidable, reduce the ZYKADIA dose by approximately one-third, rounded to the nearest multiple of the 150 mg dosage strength. Patients should be carefully moderate to severe hepatic impairment are not currently available, and therefore, agrees that ceritinib should not be recommended in patients with moderate to severe hepatic impairment. The Australian PI Dosage and Administration section [module 1.3.1.2], Precautions section [module 1.3.1.2] and section [module 1.3.1.2] have been amended to align with the EU SmPC language’. The sponsor states: ‘Novartis agrees to include in the DOSAGE AND ADMINISTRATION section of the Australian PI [module 1.3.1.2] the additional information regarding strong CYP3A inhibitors’. The sponsor states: ‘The applicant acknowledged that data regarding the potential interaction of ceritinib with pump inhibitors are not currently available and therefore agrees to add this information in the