should not be chewed or crushed. ZYKADIA capsules must be taken on an empty stomach. No food should be eaten for at least two hours before and two hours after the dose of ZYKADIA is taken (see Pharmacokinetics; Absorption). However, it is recommended to the Delegate that the last identical sentence be strengthened as follows and all these sections of the Australian PI be referenced to each other: ‘No food should be eaten for at least two hours before and two hours after the dose of ZYKADIA is taken in order to avoid the serious risk of toxicity from drug Any such change should be adequately reflected in the draft consumer medicine information document. In regard to the proposed The sponsor has This is acceptable. routine risk minimisation objected to this activities, it is recommended This is acceptable. recommendation to the Delegate that the draft This is acceptable. and provided product information justification for document be revised as This is acceptable. their position. The follows: sponsor has For the important identified concluded: risk: the ‘Hepatotoxicity’, ‘Therefore, sentence in the monthly evaluation PRECAUTIONS section of of liver laboratory the Australian PI: ‘Monitor tests is acceptable with liver laboratory tests to follow patients (including ALT, AST, and for hepatotoxicity. total bilirubin) prior to the The AU PI start of treatment and recommendation is should be monthly thereafter’ based on the US PI, amended to: with ‘Monitor the Canadian liver laboratory tests Product (including ALT, AST, and Monograph, and total bilirubin) prior to the the Swiss label’. start of treatment, every 2 weeks for the first month of The sponsor treatment and monthly states: ‘Novartis This would align thereafter’. acknowledges that with the approved EU SmPC the clinical and and enhance the safe use of exposure data in this medicine. patients with
should not be chewed or crushed. ZYKADIA capsules must be taken on an empty stomach. No food should be eaten for at least two hours before and two hours after the dose of ZYKADIA is taken (see Pharmacokinetics; Absorption). However, it is recommended to the Delegate that the last identical sentence be strengthened as follows and all these sections of the Australian PI be to each other: ‘No food should be eaten for at least two hours before and two hours after the dose of ZYKADIA is taken in order to avoid the serious risk of toxicity from drug Any such change should be adequately reflected in the draft consumer medicine information document. In regard to the proposed routine risk minimisation activities, it is recommended to the Delegate that the draft product information document be revised as follows: For the important identified risk: ‘Hepatotoxicity’, the sentence in the PRECAUTIONS section of the Australian PI: ‘Monitor with liver laboratory tests (including ALT, AST, and total bilirubin) prior to the start of treatment and monthly thereafter’ should be amended to: ‘Monitor with liver laboratory tests (including ALT, AST, and total bilirubin) prior to the start of treatment, every 2 weeks for the first month of treatment and monthly thereafter’. This would align with the approved EU SmPC and enhance the safe use of this medicine. The sponsor has objected to this recommendation and provided justification for their position. The sponsor has concluded: ‘Therefore, monthly evaluation of liver laboratory tests is acceptable to follow patients for hepatotoxicity. The AU PI recommendation is based on the US PI, the Canadian Product Monograph, and the Swiss label’. The sponsor states: ‘Novartis acknowledges that the clinical and exposure data in patients with This is acceptable. This is acceptable. This is acceptable. This is acceptable. referenced
auspar-zykadia-270218.docx