Cabometics Tablet 20 mg (Cabozantinib)

Adult dose

Treatment with this medicine should be initiated by a healthcare professional experienced in the administration of anticancer agents. Monotherapy The recommended dose is 60mg once daily. Continue treatment until the patient no longer derives clinical benefit or unacceptable toxicity occurs. First-line treatment in combination with nivolumab for advanced renal cell carcinoma The recommended dose of this medicine in combination therapy is 40mg once daily, and nivolumab is administered intravenously at 240mg every 2 weeks or 480mg every 4 weeks. Continue this medicine until disease progression or unacceptable toxicity occurs. Nivolumab is administered until disease progression or unacceptable toxicity occurs, or for a maximum of 24 months in patients without disease progression. (Refer to the prescribing information for nivolumab.) Treatment adjustments Temporary interruption of this medicine or dose reduction may be required to manage suspected adverse reactions (see Table 1). If dose reduction is required, it is recommended that the dose of this medicine be reduced to 40mg once daily for monotherapy, and then to 20mg once daily if further dose adjustment is needed. In combination therapy with nivolumab, it is recommended that the dose be reduced to 20mg once daily, and then to 20mg every other day if further dose adjustment is needed. (For dose adjustments of nivolumab, refer to its prescribing information.) Treatment interruption is recommended for CTCAE grade 3 or higher toxicity, or intolerable grade 2 toxicity. Dose reduction is recommended if severe or intolerable toxicity persists. If a patient misses a dose, the missed dose should not be taken if it is within 12 hours of the next dose. Table 1. Recommended dose modifications for adverse drug reactions Adverse drug reaction and severity Dose modification Grade 1 and Grade 2 Tolerable and easily managed Usually, no dose adjustment is required. Consider adding appropriate supportive care. Grade 2 Intolerable and cannot be managed with dose reduction or supportive care Interrupt treatment until symptoms improve to Grade 1 or lower. Add appropriate supportive care. Consider restarting at a reduced dose. Grade 3 (excluding laboratory abnormalities that are not clinically relevant) Interrupt treatment until symptoms improve to Grade 1 or lower. Add appropriate supportive care. Consider restarting at a reduced dose. Grade 4 (excluding laboratory abnormalities that are not clinically relevant) Discontinue treatment. Provide appropriate medical treatment. If symptoms improve to Grade 1 or lower, restart at a reduced dose. If symptoms do not improve, permanently discontinue this medicine. Elevated liver enzymes in patients with renal cell carcinoma treated with Cabometyx and nivolumab ALT or AST > 3 times and ≤ 10 times the ULN, with total bilirubin < 2 times the ULN Interrupt treatment with Cabometyx and nivolumab until symptoms improve to Grade 1 or lower. Corticosteroid therapy may be considered if an immune-mediated reaction is suspected (refer to the prescribing information for nivolumab). Restarting with monotherapy or sequentially restarting combination therapy after recovery may be considered. If restarting nivolumab, refer to the prescribing information for nivolumab. ALT or AST > 10 times the ULN, or > 3 times the ULN with total bilirubin ≥ 2 times the ULN Permanently discontinue Cabometyx and nivolumab. Corticosteroid therapy may be considered if an immune-mediated reaction is suspected (refer to the prescribing information for nivolumab). Note: Toxicity grades are based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE v4). Permanently discontinue this medicine in the event of the following adverse reactions: • Gastrointestinal perforation or fistula that is not adequately managed • Severe hemorrhage • Arterial thromboembolic events (e.g., myocardial infarction, cerebral infarction) • Hypertensive crisis or severe hypertension despite appropriate treatment • Nephrotic syndrome • Reversible posterior leukoencephalopathy syndrome Concomitant medications Concomitant medications that are strong CYP3A4 inhibitors should be used with caution, and chronic use of concomitant medications that are strong CYP3A4 inducers should be avoided (see section ‘1. Patients who require caution when using this medicine’ under Precautions for Use). Consider selecting alternative medications with no or minimal potential to induce or inhibit CYP3A4. Special populations Patients with renal impairment This medicine should be used with caution in patients with mild or moderate renal impairment. Use is not recommended in patients with severe renal impairment, as safety and efficacy have not been established. Patients with hepatic impairment No dose adjustment is required in patients with mild hepatic impairment; however, the recommended dose for patients with moderate hepatic impairment is 40mg once daily. Patients should be monitored for adverse drug reactions, and dose adjustment or treatment interruption should be considered as needed (refer to section ‘10. Information for healthcare professionals’ under Precautions for Use). Cabozantinib is not recommended for patients with severe hepatic impairment, as safety and efficacy have not been established. Patients with cardiac disorders Data in patients with cardiac disorders are limited. No specific dose recommendation can be made. Method of administration For oral administration. This medicine should be swallowed whole and must not be crushed. Patients should not eat for at least 2 hours before and 1 hour after taking this medicine.

This drug should not be used in patients who have allergies to the active ingredient or excipients. Additionally, as it contains lactose, it should not be administered to patients with lactose intolerance or hereditary metabolic disorders. This medication can cause various adverse reactions in patients with advanced renal cell carcinoma, hepatocellular carcinoma, differentiated thyroid cancer, and neuroendocrine tumors. The most common adverse reactions include diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and hypertension. Serious adverse reactions reported include pneumonia, gastrointestinal perforation, bleeding, thrombosis, pulmonary embolism, deep vein thrombosis, and osteonecrosis of the jaw. Hypocalcemia, hypokalemia, thrombocytopenia, hypertension, and gastrointestinal symptoms may occur during the initial treatment, so patients should be closely monitored for the first 8 weeks. Liver function abnormalities occur frequently, thus liver function tests should be conducted regularly before and during treatment. This drug can cause gastrointestinal perforations or fistulas, requiring caution in patients with a history of gastrointestinal disorders. Diarrhea is very common, and prompt treatment is required to prevent dehydration and electrolyte imbalance. There is a risk of thrombosis and bleeding, so patients with relevant medical history or symptoms should immediately consult medical personnel. Hypertension may develop; therefore, managing blood pressure before and during treatment is essential, with regular monitoring. If palmar-plantar erythrodysesthesia syndrome occurs, temporary discontinuation or dose adjustment may be necessary based on symptoms. This drug must be monitored for proteinuria and thrombocytopenia through renal function and blood tests. Rarely, reversible posterior leukoencephalopathy syndrome may occur; therefore, headache, seizures, visual disturbances, and changes in consciousness should be reported immediately. Due to the risk of QT interval prolongation, caution should be exercised for patients with cardiac diseases or those taking related medications. Women who are pregnant or likely to become pregnant should not take this medication, and male patients should also ensure their partners avoid pregnancy. Breastfeeding women should stop breastfeeding while taking this medication. This drug is metabolized by the CYP3A4 enzyme, so caution is needed when taking it with strong CYP3A4 inhibitors or inducers. Additionally, there may be interactions with P-glycoprotein and MRP2 inhibitors, so patients should inform healthcare providers. Caution is required when driving or operating machinery due to fatigue or weakness. In the case of overdose, administration should be immediately stopped, and appropriate treatment should be sought based on symptoms. This medication should be kept out of the reach of children and not transferred to other containers.

Pneumonia, gastrointestinal perforation, lupus, bleeding, thromboembolism, diarrhea, pleural effusion, pulmonary embolism, anemia, deep vein thrombosis, hypertension, hypocalcemia, jaw bone necrosis, pain, palmoplantar erythrodysesthesia syndrome, vomiting, renal impairment, hypertension, fatigue, nausea, cardiac arrest, embolism, hypoxia, decreased appetite, hypomagnesemia, hypokalemia, hypoalbuminemia, dehydration, hypophosphatemia, hyponatremia, hyperkalemia, hyperbilirubinemia, hyperglycemia, hypoglycemia, taste disturbance, headache, dizziness, peripheral neuropathy, seizures, cerebrovascular accident, reversible posterior leukoencephalopathy syndrome, tinnitus, acute myocardial infarction, hypertensive crisis, arterial thrombosis, arterial embolism, aneurysm and arterial dissection, arterial rupture, speech disorder, dyspnea, cough, allergic rhinitis, pneumothorax, nausea, stomatitis, constipation, abdominal pain, dyspepsia, gastroesophageal reflux disease, hemorrhoids, oral pain, dysphagia, dry mouth, abdominal distention, oral pain, hepatic encephalopathy, cholestatic hepatitis, rash, pruritus, hair loss, dry skin, hair color changes, hyperkeratosis, erythema, cutaneous vasculitis, limb pain, back pain, arthralgia, muscle spasms, proteinuria, mucosal inflammation, weakness, peripheral edema, fever, weight loss, increased serum ALT, increased AST, increased blood alkaline phosphatase, increased GGT, increased blood creatinine, increased amylase, increased lipase, increased blood cholesterol, decreased white blood cell count, increased blood triglycerides, wound complications, upper respiratory tract infection, eosinophilia, hypersensitivity, infusion-related hypersensitivity reaction, hyperthyroidism, adrenal insufficiency, pituitary inflammation, thyroiditis, autoimmune encephalitis, Guillain-Barré syndrome, myasthenic syndrome, dry eyes, blurred vision, uveitis, atrial fibrillation, tachycardia, myocarditis, thrombosis, nasal hemorrhage, pleural effusion, colitis, gastritis, oral pain, hemorrhoids, pruritus, psoriasis, urticaria, cutaneous vasculitis, arthritis, myopathy, kidney failure, acute kidney injury, nephritis, chest pain, hypophosphatemia, thrombocytopenia, hypercalcemia, hypermagnesemia, hypernatremia, increased blood cholesterol, hypertriglyceridemia, upper abdominal pain, edema, facial swelling, cerebral infarction, sensory disturbance, hepatic coma, hemoptysis, hiccups, vesicles, eczema, skin erosion, skin desquamation, increased blood thyroid-stimulating hormone, left ventricular dysfunction, depression, diabetes, decreased appetite, thyroid disorder, benign prostatic hyperplasia, eye swelling, hip fracture, hematuria, chronic kidney disease

This medication should be stored in a tightly sealed container to protect it from air and moisture. It is best to maintain the storage temperature between 1°C and 30°C at room temperature.

Appearance

Yellow round film-coated tablets

Package unit

30 tablets/bottle