itis cholestatic
Skin and subcutaneous tissue disorders
palmar-plantar erythrodysaesthesia syndrome, dermatitis acneiform, rash, rash maculopapular, dry skin, alopecia, hair colour change
pruritus
Musculoskeletal and connective tissue disorders
pain in extremity, muscle spasms, arthralgia
osteonecrosis of the jaw
Renal and urinary disorders
proteinuria
General disorders and administration site conditions
fatigue, mucosal inflammation, asthenia
peripheral oedema
Investigations
weight decreased, serum ALT, AST, and ALP increased, blood bilirubin increased, creatinine increased, triglycerides increased, white blood cell decreased, GGT increased, amylase increased, blood cholesterol increased, lipase increased
Injury, poisoning and procedural complications
wound complication
Description of selected adverse reactions
Data for the following reactions are based on patients who received Cabometyx 60 mg qd po in the pivotal studies in RCC following prior VEGF-targeted therapy and in treatment-naïve RCC (section 5.1).
Gastrointestinal (GI) perforation
In the study in RCC following prior VEGF-targeted therapy (METEOR), GI perforations were reported in 0.9% (3/331) of cabozantinib-treated RCC patients. Events were Grade 2 or 3. Median time to onset was 10.0 weeks.
In the treatment-naïve RCC study (CABOSUN), GI perforations were reported in 2.6% (2/78) of cabozantinib-treated patients. Events were Grade 4 and 5.
Fatal perforations have occurred in the cabozantinib clinical program.
Fistulas
In the study in RCC following prior VEGF-targeted therapy (METEOR), fistulas were reported in 1.2% (4/331) of cabozantinib-treated patients, and included anal fistulas in 0.6% (2/331) cabozantinib-treated patients. One event was Grade 3; the remainder was Grade 2. Median time to onset was 30.3 weeks.
In the treatment-naïve RCC study (CABOSUN), no cases of fistulas were reported.
Haemorrhage
In the study in RCC following prior VEGF-targeted therapy (METEOR), the incidence of severe haemorrhagic events (Grade ≥ 3) was 2.1% (7/331) in cabozantinib-treated RCC patients. Median time to onset was 20.9 weeks.
In the treatment-naïve RCC study (CABOSUN), the incidence of severe haemorrhagic events (Grade ≥ 3) was 5.1% (4/78) in cabozantinib-treated RCC patients.
Fatal haemorrhages have occurred in the cabozantinib clinical program.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
No cases of RPLS were reported in the METEOR or CABOSUN studies, but RPLS has been reported in other clinical studies with cabozantinib.
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: www.mhra.gov.uk/yellowcard
4.9 Overdose
There is no specific treatment for cabozantinib overdose and possible symptoms of overdose have not been established.
In the event of suspected overdose, cabozantinib should be withheld and supportive care instituted. Metabolic clinical laboratory parameters should be monitored at least weekly or as deemed clinically appropriate to assess any possible changing trends. Adverse reactions associated with overdose are |
