cuity reduced, accommodation disorder, presbyopia)
b Pericarditis (pericardial effusion, pericarditis)
c Bradycardia (bradycardia, sinus bradycardia)
d Pneumonitis (interstitial lung disease, pneumonitis)
e The frequency of these selected gastrointestinal ADRs (diarrhoea, nausea and vomiting) is based on patients treated with the recommended dose of ceritinib 450 mg with food (N=89) in the study A2112 (ASCEND-8) (see subsection 'Gastrointestinal adverse reactions' below)
f Abdominal pain (abdominal pain, abdominal pain upper, abdominal discomfort, epigastric discomfort)
g Oesophageal disorder (dyspepsia, gastro-oesophageal reflux disease, dysphagia)
h Abnormal liver function test (hepatic function abnormal, hyperbilirubinaemia)
i Hepatotoxicity (drug-induced liver injury, hepatitis cholestatic, hepatocellular injury, hepatotoxicity)
j Rash (rash, dermatitis acneiform, rash maculopapular)
k Renal failure (acute renal injury, renal failure)
l Renal impairment (azotaemia, renal impairment)
m Fatigue (fatigue, asthenia)
n Liver laboratory test abnormalities (alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased, blood bilirubin increased, transaminases increased, hepatic enzyme increased, liver function test abnormal, liver function test increased, blood alkaline phosphatase increased)
Elderly (≥65 years)
Across seven clinical studies, 168 out of 925 patients (18.2%) treated with Zykadia were aged 65 years or older. The safety profile in patients aged 65 years or older was similar to that in patients less than 65 years of age (see section 4.2). There are no safety data in patients older than 85 years of age.
Hepatotoxicity
Concurrent elevations of ALT or AST greater than 3× ULN and total bilirubin greater than 2× ULN without elevated alkaline phosphatase have been observed in less than 1% of patients in clinical studies with ceritinib. Increases to grade 3 or 4 ALT elevations were observed in 25% of patients receiving ceritinib. Hepatotoxicity events were managed with dose interruptions or reductions in 40.6% of patients. 1% of patients required permanent discontinuation of treatment in clinical studies with ceritinib (see sections 4.2 and 4.4).
Liver laboratory tests including ALT, AST and total bilirubin should be performed prior to the start of treatment, every 2 weeks during the first three months of treatment and monthly thereafter, with more frequent testing for grade 2, 3 or 4 elevations. Patients should be monitored for liver laboratory test abnormalities and managed as recommended in sections 4.2 and 4.4.
Gastrointestinal adverse reactions
Nausea, diarrhoea and vomiting were among the most commonly reported gastrointestinal events. In the dose optimisation study A2112 (ASCEND-8) in both previously treated and untreated patients with ALK-positive advanced NSCLC at the recommended dose of ceritinib 450 mg taken with food (N=89), adverse events of diarrhoea, nausea and vomiting were mainly grade 1 (49.4%). A grade 3 event of diarrhoea was reported in one patient (1.1%). Gastrointestinal events were managed primarily with concomitant medicinal products including anti-emetic/anti-diarrhoeal medicinal products. Seven patients (7.9%) required study drug interruption due to diarrhoea or nausea. No patients had diarrhoea, nausea, or vomiting that required dose reductio |
