ing those patients taking anti-arrhythmic medicinal products such as class I (e.g. quinidine, procainamide, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) anti-arrhythmics or other medicinal products that may lead to QT prolongation such as domperidone, droperidol, chloroquine, halofantrine, clarithromycin, haloperidol, methadone, cisapride and moxifloxacin. Monitoring of the QT interval is indicated in the event of combinations of such medicinal products (see sections 4.2 and 4.4).
Food/drink interactions
Zykadia should be taken with food. The bioavailability of ceritinib is increased in the presence of food.
For patients who develop a concurrent medical condition and are unable to take Zykadia with food, Zykadia can be taken on an empty stomach as the alternate continued treatment regimen, in which no food should be eaten for at least two hours before and one hour after the dose. Patients should not alternate between fasted and fed dosing. Dose must be adjusted properly, i.e for patients treated with 450 mg or 300 mg with food, the dose should be increased to 750 mg or 450 mg taken on an empty stomach, respectively (see section 5.2) and for patients treated with 150 mg with food treatment should be discontinued. For subsequent dose adjustment and management recommendations for ADRs, please follow table 1 (see section 4.2). The maximum allowable dose under fasted condition is 750 mg (see section 5.2).
Patients should be instructed to avoid grapefruit and grapefruit juice as they may inhibit CYP3A in the gut wall and may increase the bioavailability of ceritinib.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential
Women of childbearing potential should be advised to use a highly effective method of contraception while taking Zykadia and for up to 3 months after discontinuing treatment (see section 4.5).
Pregnancy
There are no or limited amount of data from the use of ceritinib in pregnant women.
Animal studies are insufficient with respect to reproductive toxicity (see section 5.3).
Zykadia should not be used during pregnancy unless the clinical condition of the woman requires treatment with ceritinib.
Breast-feeding
It is unknown whether ceritinib/metabolites are excreted in human milk. A risk to the newborn/infant cannot be excluded.
A decision must be made whether to discontinue breast-feeding or discontinue/abstain from Zykadia therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman (see section 5.3).
Fertility
The potential for Zykadia to cause infertility in male and female patients is unknown (see section 5.3).
4.7 Effects on ability to drive and use machines
Zykadia has minor influence on the ability to drive or use machines. Caution should be exercised when driving or using machines during treatment as patients may experience fatigue or vision disorders.
4.8 Undesirable effects
Summary of the safety profile
Adverse drug reactions (ADRs) described below reflect exposure to Zykadia 750 mg once daily fasted in 925 patients with ALK-positive advanced NSCLC across a pool of seven clinical studies including two randomised, active-controlled, phase 3 studies (studies A2301 and A2303).
The median duration of exposure to Zykadia 750 mg fasted was 44.9 weeks (range: 0.1 to 200.1 weeks).
ADRs with an incidence of ≥10% in patients treated with Zykadia 750 mg fasted were diarrhoea, nausea, vomit |
