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Cabometyx is a brand name for Cabozantinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Renal cell carcinoma (RCC) CABOMETYX is indicated as monotherapy for advanced renal cell carcinoma - as first-line treatment of adult patients with intermediate or poor risk (see section 5.1), - in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy (see section 5.1). CABOMETYX, in…
Verbatim from this product's EMA label. Tap a section to expand.
Therapy with CABOMETYX should be initiated by a physician experienced in the administration of anticancer medicinal products. 2). CABOMETYX as monotherapy For RCC, HCC, DTC and NET, 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. CABOMETYX in combination with nivolumab in first-line advanced RCC The recommended dose of CABOMETYX is 40 mg once daily in combination with nivolumab solution for infusion administered intravenously at either 240 mg every 2 weeks or 480 mg every 4 weeks, or with nivolumab solution for injection administered subcutaneously at either 600 mg every 2 weeks or 1200 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).
4 Treatment modification 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.
Cabozantinib as monotherapy Summary of safety profile The most common serious adverse drug reactions in the RCC population (≥1% incidence) are pneumonia, abdominal pain, diarrhoea, nausea, hypertension, embolism, hyponatraemia, pulmonary embolism, vomiting, dehydration, fatigue, asthenia, decreased appetite, deep vein thrombosis, dizziness, hypomagnesaemia and palmar-plantar erythrodysaesthesia syndrome (PPES).
The most common serious adverse drug reactions in the HCC population (≥1% incidence) are hepatic encephalopathy, asthenia, fatigue, PPES, diarrhoea, hyponatraemia, vomiting, abdominal pain and thrombocytopenia. The most common serious adverse drug reactions in the DTC population (≥1% incidence) are diarrhoea, pleural effusion, pneumonia, pulmonary embolism, hypertension, anaemia, deep vein thrombosis, hypocalcaemia, osteonecrosis of jaw, pain, PPES, vomiting and renal impairment.
The most common serious adverse drug reactions in the NET population (≥1% incidence) are hypertension, fatigue, pulmonary embolism, vomiting, diarrhoea, nausea and embolism. The most frequent adverse reactions of any grade (experienced by at least 25% of patients) in the RCC, HCC, DTC and NET populations were diarrhoea, fatigue, nausea, decreased appetite, PPES and hypertension.
Tabulated list of adverse reactions Adverse reactions reported in the pooled dataset for patients treated with cabozantinib monotherapy in RCC, HCC, DTC and NET (n=1355) or reported after post-marketing use of cabozantinib are listed in Table 2.
The adverse reactions are listed by MedDRA system organ class and frequency categories. Frequencies are based on all grades and defined as: very common (≥1/10), common (≥1/100 to 12 <1/10); uncommon (≥1/1,000 to <1/100); not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 8 Description of selected adverse reactions for further characterisation. a including polyneuropathy; peripheral neuropathy is mainly sensory b Including epistaxis as the most commonly reported adverse reaction cAll venous thrombosis including deep vein thrombosis d Based on reported adverse reactions e Impaired healing, incision site complication and wound dehiscence f Rash is a composite term which includes dermatitis, dermatitis acneiform, dermatitis bullous, exfoliative rash, rash erythematous, rash follicular, rash macular, rash maculo-papular, rash papular, rash pruritic and drug eruption.
As most adverse reactions occur early in the course of treatment, the physician should evaluate the patient closely during the first eight weeks of treatment to determine if dose modifications are warranted. Adverse reactions that generally have early onset include hypocalcaemia, hypokalaemia, thrombocytopenia, hypertension, palmar-plantar erythrodysaesthesia syndrome (PPES), proteinuria, and gastrointestinal (GI) events (abdominal pain, mucosal inflammation, constipation, diarrhoea, vomiting).
2): Dose reductions and dose interruptions due to an adverse event (AE) occurred in 46-67% and 70- 84%, respectively, of cabozantinib-treated patients in the pivotal monotherapy clinical trials in RCC (METEOR, CABOSUN), HCC (CELESTIAL), DTC (COSMIC-311) and NET (CABINET).
4%-33% of patients. The median time to first dose reduction was 38-106 days and to first dose interruption was 28-68 days. 4% of patients in the clinical trial (CA2099ER). 4% of patients. The median time to first dose reduction was 106 days, and to first dose interruption was 68 days.
Hepatotoxicity Abnormalities of liver function tests (increases in alanine aminotransferase [ALT], aspartate aminotransferase [AST] and bilirubin) have been frequently observed in patients treated with cabozantinib. It is recommended to perform liver function tests (ALT, AST and bilirubin) before initiation of cabozantinib treatment and to monitor closely during treatment.
e. 2). 8). Liver enzymes should be monitored before initiation of and periodically throughout treatment. 2 and refer to the SmPC for nivolumab). Rare instances of vanishing bile duct syndrome have been reported. All cases have occurred in patients who have received immune checkpoint inhibitors, either before or concurrently with cabozantinib treatment.
Cabozantinib is eliminated mainly via the hepatic route. 2). A higher relative proportion of patients with moderate hepatic impairment (Child-Pugh B) developed hepatic encephalopathy with cabozantinib treatment. 2). Hepatic encephalopathy In the HCC study (CELESTIAL), hepatic encephalopathy was reported more frequently in the cabozantinib than the placebo arm.
1. 6
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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. 5 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). 5). Selection of an alternative concomitant medicinal product with no or minimal potential to induce or inhibit CYP3A4 should be considered.
Special populations Elderly No specific dose adjustment for the use of cabozantinib in elderly patients (≥ 65 years) is recommended. 2) 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. Hepatic impairment 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. 2). 2). Cardiac impairment There are 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. 2 but no recommendation on a posology can be made. 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 […]
g Fatal cases have been reported Cabozantinib in combination with nivolumab in first-line advanced RCC Summary of safety profile When cabozantinib is administered in combination with nivolumab, refer to the SmPC for nivolumab prior to initiation of treatment.
For additional information on the safety profile of nivolumab monotherapy, please refer to the nivolumab SmPC. In a dataset of cabozantinib 40 mg once daily in combination with nivolumab 240 mg every two weeks in RCC (n =320), with a minimum follow‑up of 16 months, the most common serious adverse drug reactions (≥1% incidence) are diarrhoea, pneumonitis, pulmonary embolism, pneumonia, hyponatraemia, pyrexia, adrenal insufficiency, vomiting, dehydration.
The most frequent adverse reactions (≥25%) were diarrhoea, fatigue, palmar-plantar erythrodysaesthesia syndrome, stomatitis, musculoskeletal pain, hypertension, rash, hypothyroidism, […]
Cabozantinib has been associated with diarrhoea, vomiting, decreased appetite and electrolyte abnormalities. In HCC patients with compromised livers, these non-hepatic effects may be precipitating factors for the development of hepatic encephalopathy.
Patients should be monitored for signs and symptoms of hepatic encephalopathy. Perforations and fistulas Serious GI perforations and fistulas, sometimes fatal, have been observed with cabozantinib. , Crohn’s disease, ulcerative colitis, peritonitis, 7 diverticulitis, or appendicitis), have tumour infiltration in the GI tract, or have complications from prior GI surgery (particularly when associated with delayed or incomplete healing) should be carefully evaluated before initiating cabozantinib therapy and subsequently they should be monitored closely for symptoms of perforations and fistulas including abscesses and sepsis.
Persistent or recurring diarrhoea while on treatment may be a risk factor for the development of anal fistula. Cabozantinib should be discontinued in patients who experience a GI perforation or a fistula that cannot be adequately managed.
8). Prompt medical management, including supportive care with antiemetics, antidiarrhoeals, or antacids, should be instituted to prevent dehydration, electrolyte imbalances and weight loss. Dose interruption or reduction, or permanent discontinuation of cabozantinib should be considered in case of persistent or recurrent significant GI adverse reactions (see Table 1).
Thromboembolic events Events of venous thromboembolism, including pulmonary embolism, and arterial thromboembolism, sometimes fatal, have been observed with cabozantinib. Cabozantinib should be used with caution in patients who are at risk for, or who have a history of, these events.
In the HCC study (CELESTIAL), portal vein thrombosis was observed with cabozantinib, including one fatal event. Patients with a history of portal vein invasion appeared to be at higher risk of developing portal vein thrombosis. Cabozantinib should be discontinued in patients who develop an acute myocardial infarction or any other clinically significant thromboembolic complication.
8%) in participants who received cabozantinib. Haemorrhage Severe haemorrhage, sometimes fatal, has been observed with cabozantinib. Patients who have a history of severe bleeding prior to treatment […]