ing, fatigue, liver laboratory test abnormalities, abdominal pain, decreased appetite, weight decreased, constipation, blood creatinine increased, rash, anaemia and oesophageal disorder.
Grade 3-4 ADRs with an incidence of ≥5% in patients treated with Zykadia 750 mg fasted were liver laboratory test abnormalities, fatigue, vomiting, hyperglycaemia, nausea and diarrhoea.
In the dose optimisation study A2112 (ASCEND-8) in both previously treated and untreated patients with ALK-positive advanced NSCLC, the overall safety profile of Zykadia at the recommended dose of 450 mg with food (N=89) was consistent with Zykadia 750 mg fasted (N=90), except for a reduction in gastrointestinal adverse drug reactions, while achieving comparable steady-state exposure (see section 5.1 and subsection 'Gastrointestinal adverse reactions' below).
Tabulated list of ADRs
Table 2 shows the frequency category of ADRs reported for Zykadia in patients treated at a dose of 750 mg fasted (N=925) in seven clinical studies. The frequency of selected gastrointestinal ADRs (diarrhoea, nausea and vomiting) are based on patients treated with a dose of 450 mg once-daily with food (N=89).
ADRs are listed according to MedDRA system organ class. Within each system organ class, the ADRs are ranked by frequency, with the most frequent reactions first. In addition, the corresponding frequency category using the following convention (CIOMS III) is also provided for each ADR: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from the available data).
Table 2 ADRs in patients treated with Zykadia
System organ class
Preferred term
Zykadia
N=925
%
Frequency category
Blood and lymphatic system disorders
Anaemia
15.2
Very common
Metabolism and nutrition disorders
Decreased appetite
39.5
Very common
Hyperglycaemia
9.4
Common
Hypophosphataemia
5.3
Common
Eye disorders
Vision disordera
7.0
Common
Cardiac disorders
Pericarditisb
5.8
Common
Bradycardiac
2.3
Common
Respiratory, thoracic and mediastinal disorders
Pneumonitisd
2.1
Common
Gastrointestinal disorders
Diarrhoeae
56.2
Very common
Nauseae
44.9
Very common
Vomitinge
34.8
Very common
Abdominal painf
46.1
Very common
Constipation
24.0
Very common
Oesophageal disorderg
14.1
Very common
Pancreatitis
0.5
Uncommon
Hepatobiliary disorders
Abnormal liver function testsh
2.2
Common
Hepatotoxicityi
1.1
Common
Skin and subcutaneous tissue disorders
Rashj
19.6
Very common
Renal and urinary disorders
Renal failurek
1.8
Common
Renal impairmentl
1.0
Common
General disorders and administration site conditions
Fatiguem
48.4
Very common
Investigations
Liver laboratory test abnormalitiesn
60.5
Very common
Weight decreased
27.6
Very common
Blood creatinine increased
22.1
Very common
Electrocardiogram QT prolonged
9.7
Common
Lipase increased
4.8
Common
Amylase increased
7.0
Common
Includes cases reported within the clustered terms:
a Vision disorder (vision impairment, vision blurred, photopsia, vitreous floaters, visual a |
