der adding supportive care as indicated.
Grade 2 adverse reactions which are intolerable and cannot be managed with a dose reduction or supportive care
Interrupt treatment until the adverse reaction resolves to Grade ≤1.
Add supportive care as indicated.
Consider re-initiating at a reduced dose.
Grade 3 adverse reactions (except clinically nonrelevant laboratory abnormalities)
Interrupt treatment until the adverse reaction resolves to Grade ≤1.
Add supportive care as indicated.
Re-initiate at a reduced dose.
Grade 4 adverse reactions (except clinically nonrelevant laboratory abnormalities)
Interrupt treatment.
Institute appropriate medical care.
If adverse reaction resolves to Grade ≤1, re-initiate at a reduced dose.
If adverse reaction does not resolve, permanently discontinue CABOMETYX.
Note: Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4)
Concomitant medicinal products
Concomitant medicinal products that are strong inhibitors of CYP3A4 should be used with caution, and chronic use of concomitant medicinal products that are strong inducers of CYP3A4 should be avoided (see sections 4.4 and 4.5).
Selection of an alternative concomitant medicinal product with no or minimal potential to induce or inhibit CYP3A4 should be considered.
Special populations
Elderly patients
No specific dose adjustment for the use of cabozantinib in older people (≥ 65 years) is recommended.
Race
There is little experience with cabozantinib in non-White patients.
Patients with renal impairment
Cabozantinib should be used with caution in patients with mild or moderate renal impairment.
Cabozantinib is not recommended for use in patients with severe renal impairment as safety and efficacy have not been established in this population.
Patients with hepatic impairment
In patients with mild or moderate hepatic impairment the recommended dose is 40 mg once daily. Patients should be monitored for adverse events and dose adjustment or treatment interruption should be considered as needed (see section 4.2). Cabozantinib is not recommended for use in patients with severe hepatic impairment as safety and efficacy have not been established in this population.
Patients with cardiac impairment
There is limited data in patients with cardiac impairment. No specific dosing recommendations can be made.
Paediatric population
The safety and efficacy of cabozantinib in children and adolescents aged <18 years have not yet been established. No data are available.
Method of administration
CABOMETYX is for oral use. The tablets should be swallowed whole and not crushed. Patients should be instructed to not eat anything for at least 2 hours before, through 1 hour after, taking CABOMETYX.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
As most events can occur early in the course of treatment, the physician should eva luate the patient closely during the first eight weeks of treatment to determine if dose modifications are warranted. Events that generally have early onset include hypocalcaemia, hypokalaemia, thrombocytopenia, hypertension, palmar-plantar erythrodysaesthesia syndrome (PPES), proteinuria, and gastrointestinal (GI) events (abdominal pain |
