response. An improvement in survival or symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in If confirmatory trials’. applicable, it is recommended to the Delegate that similar statements alluding to an absence of efficacy data be included in the Indications section of the Australian PI. Any such change should be adequately reflected in the draft consumer medicine information document. As previously stated The sponsor has The sponsor’s consideration must be given objected to this overall proposed as to what risk minimisation wording and approach to this activities will be proposed proposed matter is generally for the new important alternative acceptable, although potential risk: ‘Toxicity wording as it is recommended from drug over-exposure follows: food to the Delegate that ‘No when taken with food’. It is should be eaten for the following text acknowledged that the at least two hours from the following routine risk before and two corresponding US minimisation is already hours after the FDA monograph be included under the dose of ZYKADIA is included in the interactions’ taken in order to Pharmacokinetics; subheading and in the avoid systemic Absorption section Dosage and Administration exposure exceeding of the Australian PI: section of the draft that of a 750 mg 600 mg or higher ‘A Australian PI respectively: ZYKADIA dose ZYKADIA dose taken The bioavailability of taken in the fasted with a meal is ceritinib is increased in the state, which may expected to result in presence of food depending increase adverse systemic exposure on the fat content in the drug reactions’. exceeding that of a meal (see 750 mg ZYKADIA Pharmacokinetics; dose taken in the Absorption). Ceritinib fasted state, and may should be trial on an empty increase adverse stomach. No food should be drug reactions’. The eaten for at least two hours ASA should be before and two hours after amended the dose of ZYKADIA is accordingly, taken. preferably before ZYKADIA should be administered orally once this application is daily at the same time every approved. day. ZYKADIA capsules should be swallowed whole with water. The capsules
response. An improvement in survival or symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials’. If applicable, it is recommended to the Delegate that similar statements alluding to an absence of efficacy data be included in the Indications section of the Australian PI. Any such change should be adequately reflected in the draft consumer medicine information document. As previously stated consideration must be given as to what risk minimisation activities will be proposed for the new important potential risk: ‘Toxicity from drug over-exposure when taken with food’. It is acknowledged that the following routine risk minimisation is already included under the interactions’ subheading and in the Dosage and Administration section of the draft Australian PI respectively: The bioavailability of ceritinib is increased in the presence of food depending on the fat content in the meal (see Pharmacokinetics; Absorption). Ceritinib should be 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. ZYKADIA should be administered orally once daily at the same time every day. ZYKADIA capsules should be swallowed whole with water. The capsules The sponsor has objected to this wording and proposed alternative wording as follows: ‘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 systemic exposure exceeding that of a 750 mg ZYKADIA dose taken in the fasted state, which may increase adverse drug reactions’. The sponsor’s overall proposed approach to this matter is generally acceptable, although it is recommended to the Delegate that the following text from the corresponding US FDA monograph be included in the Pharmacokinetics; Absorption section of the Australian PI: ‘A 600 mg or higher ZYKADIA dose taken with a meal is expected to result in systemic exposure exceeding that of a 750 mg ZYKADIA dose taken in the fasted state, and may increase adverse drug reactions’. The ASA should be amended accordingly, preferably before this application is approved. trial
auspar-zykadia-270218.docx