n or discontinuation of study drug. The incidence and severity of gastrointestinal adverse drug reactions were reduced for patients treated with Zykadia 450 mg with food (diarrhoea 56%, nausea 45%, vomiting 35%; 1.1% reported a grade 3/4 event) compared to 750 mg fasted (diarrhoea 76%, nausea 50%, vomiting 56%; 12% reported a grade 3/4 event). Patients should be managed as recommended in sections 4.2 and 4.4.
QT interval prolongation
QTc prolongation has been observed in patients treated with ceritinib. Across the seven clinical studies, 9.7% of patients treated with ceritinib had events of QT prolongation (any grade), including grade 3 or 4 events in 2.1% of patients. These events required dose reduction or interruption in 2.1% of patients and led to discontinuation in 0.2% of patients.
Treatment with ceritinib is not recommended in patients who have congenital long QT syndrome or who are taking medicinal products known to prolong the QTc interval (see sections 4.4 and 4.5). Particular care should be exercised when administering ceritinib to patients with an increased risk of experiencing torsade de pointes during treatment with a QTc-prolonging medicinal product.
Patients should be monitored for QT prolongation and managed as recommended in sections 4.2 and 4.4.
Bradycardia
Across the seven clinical studies, bradycardia and/or sinus bradycardia (heart rate less than 60 bpm) events (all grade 1) were reported in 2.3% of patients. These events required dose reduction or interruption in 0.2% of patients. None of these events led to discontinuation of ceritinib treatment. The use of concomitant medicinal products associated with bradycardia should be carefully eva luated. Patients who develop symptomatic bradycardia should be managed as recommended in sections 4.2 and 4.4.
Interstitial lung disease/Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis have been observed in patients treated with ceritinib. Across the seven clinical studies, any grade ILD/pneumonitis has been reported in 2.1% of patients treated with ceritinib, and grade 3 or 4 events have been reported in 1.2% of patients. These events required dose reduction or interruption in 1.1% of patients and led to discontinuation in 0.9% of patients. Patients with pulmonary symptoms indicative of ILD/pneumonitis should be monitored. Other potential causes of ILD/pneumonitis should be excluded (see sections 4.2 and 4.4).
Hyperglycaemia
Hyperglycaemia (all grades) was reported in 9.4% of patients treated with ceritinib across the seven clinical studies; grade 3 or 4 events were reported in 5.4% of patients. These events required dose reduction or interruption in 1.4% of patients and led to discontinuation in 0.1% of patients. The risk of hyperglycaemia was higher in patients with diabetes mellitus and/or concurrent steroid use. Monitoring of fasting serum glucose is required prior to the start of ceritinib treatment and periodically thereafter as clinically indicated. Administration of anti-hyperglycaemic medicinal products should be initiated or optimised as indicated (see sections 4.2 and 4.4).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: ww |
