er medicinal products, the Summary of Product Characteristics (SmPC) for the other product must be consulted for the recommendations regarding co-administration with CYP3A4 inhibitors.
Co-administration of ceritinib with substrates primarily metabolised by CYP3A or CYP3A substrates known to have narrow therapeutic indices (e.g. alfuzosin, amiodarone, cisapride, ciclosporin, dihydroergotamine, ergotamine, fentanyl, pimozide, quetiapine, quinidine, lovastatin, simvastatin, sildenafil, midazolam, triazolam, tacrolimus, alfentanil and sirolimus) should be avoided and alternative medicinal products that are less sensitive to CYP3A4 inhibition should be used if possible. If unavoidable, dose reduction for co-administered medicinal products that are CYP3A substrates with narrow therapeutic indices should be considered.
Special populations
Renal impairment
A dedicated pharmacokinetic study in patients with renal impairment has not been conducted. However, based on available data, ceritinib elimination via the kidney is negligible. Therefore, no dose adjustment is necessary in patients with mild to moderate renal impairment. Caution should be used in patients with severe renal impairment, as there is no experience with ceritinib in this population (see section 5.2).
Hepatic impairment
Based on available data, ceritinib is eliminated primarily via the liver. Particular caution should be exercised when treating patients with severe hepatic impairment and the dose should be reduced by approximately one third, rounded to the nearest multiple of the 150 mg dosage strength (see sections 4.4 and 5.2). No dose adjustment is necessary in patients with mild or moderate hepatic impairment.
Elderly (≥65 years)
The limited data on the safety and efficacy of ceritinib in patients aged 65 years and older do not suggest that a dose adjustment is required in elderly patients (see section 5.2). There are no available data on patients over 85 years of age.
Paediatric population
The safety and efficacy of ceritinib in children and adolescents aged up to 18 years have not been established. No data are available.
Method of administration
Zykadia is for oral use. The capsules should be administered orally once daily with food at the same time every day. It is important that Zykadia is taken with food to reach the appropriate exposure. Food can range from a light to a full meal (see section 5.2).
For patients who develop a concurrent medical condition and are unable to take Zykadia with food please refer to section 4.5.
The capsules should be swallowed whole with water and should not be chewed or crushed.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Hepatotoxicity
Cases of hepatotoxicity occurred in 1.1% of patients receiving ceritinib in clinical studies. Increases to grade 3 or 4 ALT elevations were observed in 25% of patients. The majority of cases were manageable with dose interruption and/or dose reduction. Few events required discontinuation of treatment.
Patients should be monitored with liver laboratory tests (including ALT, AST and total bilirubin) prior to the start of treatment, every 2 weeks during the first three months of treatment and monthly thereafter. In patients who develop transaminase elevations, more frequent monitoring of liver transaminases and total bilirubin should be carried out |
