n 5.3). The potential risk for humans is unknown. Cabozantinib should not be used during pregnancy unless the clinical condition of the woman requires treatment with cabozantinib.
Breast-feeding
It is not known whether cabozantinib and/or its metabolites are excreted in human milk. Because of the potential harm to the infant, mothers should discontinue breast-feeding during treatment with cabozantinib, and for at least 4 months after completing therapy.
Fertility
There are no data on human fertility. Based on non-clinical safety findings, male and female fertility may be compromised by treatment with cabozantinib (see section 5.3). Both men and women should be advised to seek advice and consider fertility preservation before treatment.
4.7 Effects on ability to drive and use machines
Cabozantinib has minor influence on the ability to drive and use machines. Adverse reactions such as fatigue and weakness have been associated with cabozantinib. Therefore, caution should be recommended when driving or operating machines.
4.8 Undesirable effects
Summary of safety profile
The most common serious adverse drug reactions are hypertension, diarrhoea, palmar-plantar erythrodysaesthesia syndrome (PPES), pulmonary embolism, fatigue and hypomagnesaemia.
The most frequent adverse reactions of any grade (experienced by at least 25% of patients) included diarrhoea, hypertension, fatigue, AST increased, ALT increased, nausea, decreased appetite, PPES, dysgeusia, platelet count decreased, stomatitis, anaemia, vomiting, weight decreased, dyspepsia, and constipation. Hypertension was observed more frequently in the treatment naïve RCC population (67%) compared to RCC patients following prior VEGF-targeted therapy (37%).
Tabulated list of adverse reactions
Adverse reactions are listed in Table 2 according to MedDRA System Organ Class and frequency categories. Frequencies are based on all grades and defined as: very common (≥1/10), common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100.Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 2: Adverse drug reactions (ADRs) reported with cabozantinib in advanced RC
MedDRA System Organ Class
Very Common
Common
Uncommon
Not Known
Infections and infestations
abscess
Blood and lymphatic disorders
anaemia, lymphopenia, neutropenia, thrombocytopenia
Endocrine disorders
hypothyroidism
Metabolism and nutrition disorders
dehydration, decreased appetite, hyperglycaemia, hypoglycaemia hypophosphataemia, hypoalbuminaemia, hypomagnesaemia, hyponatraemia, hypokalaemia, hyperkalaemia, hypocalcaemia, hyperbilirubinemia.
Nervous system disorders
peripheral sensory neuropathy, dysgeusia, headache, dizziness
convulsion
cerebrovascular accident
Ear and labyrinth disorders
tinnitus
Cardiac disorders
myocardial infarction
Vascular disorders
hypertension
venous thrombosis
arterial thrombosis
Respiratory, thoracic, and mediastinal disorders
dysphonia, dyspnoea, cough
pulmonary embolism
Gastrointestinal disorders
diarrhoea, nausea, vomiting, stomatitis, constipation, abdominal pain, dyspepsia, oral pain, dry mouth
pancreatitis, abdominal pain upper, gastro-oesophageal reflux disease, haemorrhoids
anal fistula
Hepatobiliary disorders
hepat |
