Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Ipsen Pharma, 70 rue Balard, 75015 Paris, France
CABOMETYX is indicated as monotherapy for advanced renal cell carcinoma
CABOMETYX, in combination with nivolumab, is indicated for the first-line treatment of advanced renal cell carcinoma in adults (see section 5.1).
CABOMETYX is indicated as monotherapy for the treatment of hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib.
CABOMETYX is indicated as monotherapy for the treatment of adult patients with locally advanced or metastatic differentiated thyroid carcinoma (DTC), refractory or not eligible to radioactive iodine (RAI) who have progressed during or after prior systemic therapy.
Therapy with CABOMETYX should be initiated by a physician experienced in the administration of anticancer medicinal products.
CABOMETYX tablets and cabozantinib capsules are not bioequivalent and should not be used interchangeably (see section 5.2).
For RCC, HCC and DTC, the recommended dose of CABOMETYX is 60 mg once daily.
Treatment should continue until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs.
The recommended dose of CABOMETYX is 40 mg once daily in combination with nivolumab administered intravenously at either 240 mg every 2 weeks or 480 mg every 4 weeks. The treatment should continue until disease progression or unacceptable toxicity. Nivolumab should be continued until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression (see the Summary of Product Characteristics (SmPC) for posology of nivolumab).
Management of suspected adverse drug reactions may require temporary treatment interruption and/or dose reduction (see Table 1). When dose reduction is necessary in monotherapy, it is recommended to reduce to 40 mg daily, and then to 20 mg daily.
When CABOMETYX is administered in combination with nivolumab, it is recommended to reduce the dose to 20 mg of CABOMETYX once daily, and then to 20 mg every other day (refer to the nivolumab SmPC for recommended treatment modification for nivolumab).
Dose interruptions are recommended for management of CTCAE grade 3 or greater toxicities or intolerable grade 2 toxicities. Dose reductions are recommended for events that, if persistent, could become serious or intolerable.
If a patient misses a dose, the missed dose should not be taken if it is less than 12 hours before the next dose.
Table 1. Recommended CABOMETYX dose modifications for adverse reactions:
| Adverse reaction and severity | Treatment modification |
|---|---|
| Grade 1 and grade 2 adverse reactions which are tolerable and easily managed | Dose adjustment is usually not required. Add 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 the treatment. |
| Liver enzymes elevations for RCC patients treated with CABOMETYX in combination with nivolumab | |
| ALT or AST > 3 times ULN but ≤10 times ULN without concurrent total bilirubin ≥ 2 times ULN | Interrupt CABOMETYX and nivolumab until these adverse reactions resolves to Grade≤1 Corticosteroid therapy may be considered if immune- mediated reaction is suspected (refer to nivolumab SmPC). Re-initiate with a single medicine or sequential re- initiating with both medicines after recovery may be considered. If re-initiating with nivolumab, refer to nivolumab SmPC. |
| ALT or AST > 10 times ULN or > 3 times ULN with concurrent total bilirubin ≥ 2 times ULN | Permanently discontinue CABOMETYX and nivolumab. Corticosteroid therapy may be considered if immune- mediated reaction is suspected (refer to nivolumab SmPC). |
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 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.
No specific dose adjustment for the use of cabozantinib in elderly patients (≥65 years) is recommended.
No dose adjustment is necessary based on ethnicity (see section 5.2).
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.
In patients with mild hepatic impairment no dose adjustment is required. Since only limited data are available for patients with moderate hepatic impairment (Child Pugh B), no dosing recommendation can be provided. Close monitoring of overall safety is recommended in these patients (see sections 4.4 and 5.2). There is no clinical experience in patients with severe hepatic impairment (Child Pugh C), so cabozantinib is not recommended for use in these patients (see section 5.2).
There are limited data in patients with cardiac impairment. No specific dosing recommendations can be made.
The safety and efficacy of cabozantinib in children and adolescents aged <18 years have not yet been established. Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.
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.
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 to be treated symptomatically.
4 years.
This medicinal product does not require any special storage conditions.
HDPE bottle with a polypropylene child-resistant closure, three silica gel desiccant canisters and polyester coil. Each bottle contains 30 film-coated tablets.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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