Cabometyx 60 mg (Cabozantinib)

Adult dose

Treatment with this medicine should be initiated by a healthcare professional experienced in administering anticancer agents. Monotherapy The recommended dose is 60mg once daily. Treatment with this medicine should continue 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 by intravenous infusion at 240mg every 2 weeks or 480mg every 4 weeks. This medicine should be continued until disease progression or unacceptable toxicity occurs. Nivolumab should be administered until disease progression or unacceptable toxicity occurs, or for a maximum of 24 months in patients without disease progression. (See the prescribing information for nivolumab.) Treatment modification 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 in monotherapy and, if further dose modification is required, reduced to 20mg once daily. In combination therapy with nivolumab, it is recommended that the dose be reduced to 20mg once daily and, if further dose modification is required, reduced to 20mg every other day. (For nivolumab dose modifications, see 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 modification is required. Consider adding appropriate supportive care. Grade 2 Intolerable and not manageable 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 in combination with nivolumab ALT or AST >3 times and ≤10 times ULN, with total bilirubin <2 times 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 (see 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 ULN or >3 times ULN with total bilirubin ≥2 times ULN Permanently discontinue Cabometyx and nivolumab. Corticosteroid therapy may be considered if an immune-mediated reaction is suspected (see 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 requiring caution’ under Precautions for Use). Selection of alternative medications with no or minimal potential to induce or inhibit CYP3A4 should be considered. 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 the safety and efficacy of this medicine have not been established in these patients. Patients with hepatic impairment No dose adjustment is required in patients with mild hepatic impairment; however, the recommended dose in 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 (see ‘10. Information for healthcare professionals’ under Precautions for Use). Cabozantinib is not recommended in patients with severe hepatic impairment, as its safety and efficacy have not been established in these patients. 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 consume food for at least 2 hours before and 1 hour after taking this medicine.

This medication should not be used in patients who are allergic to the active ingredient or excipients or who have a genetic inability to break down lactose. Serious side effects such as pneumonia, gastrointestinal perforation, bleeding, and thromboembolism may occur during treatment with this medication; caution is required. Common side effects such as diarrhea, hypertension, fatigue, nausea, and sensory disturbances in the palms and soles may appear; if symptoms are severe, the patient should consult a healthcare provider immediately. This medication may affect liver function, so liver function tests should be conducted regularly before and during treatment. Patients with a history of gastrointestinal diseases should be particularly cautious as fatal gastrointestinal perforation or bleeding, or abnormal leaks may occur. Patients with hypertension or at risk for thromboembolism should carefully monitor their blood pressure and blood status before and after taking this medication. During treatment, adverse reactions such as thrombocytopenia, hypothyroidism, and electrolyte imbalances may occur, so regular testing is necessary. If a dental surgery or invasive procedure is planned, this medication should be discontinued at least 28 days prior to the procedure, and the wound healing status should be monitored. Women who are pregnant or planning to become pregnant, as well as partners of male patients taking this medication should avoid pregnancy and use effective contraception for at least 4 months during and after treatment. This medication has not been proven safe and effective in children under 18 years of age and should not be used in this population. In case of overdose, treatment should be stopped immediately, and appropriate care should be provided according to symptoms; no specific antidote exists. This medication does not require special storage conditions; however, it should be kept out of reach of children, and transferring it to other containers should be avoided. Fatigue and weakness may occur during therapy; caution is advised when driving or operating machinery.

Pneumonia, gastrointestinal perforation, lupus, hemorrhage, thromboembolism, diarrhea, pleural effusion, pulmonary embolism, anemia, deep vein thrombosis, hypertension, hypocalcemia, jaw osteonecrosis, pain, palmar-plantar erythrodysesthesia syndrome, vomiting, renal dysfunction, hypertension, fatigue, nausea, cardiac arrest, embolism, hypoxia, abscess, hepatic encephalopathy, dysgeusia, headache, dizziness, seizures, cerebrovascular accident, tinnitus, acute myocardial infarction, hemorrhage, venous thrombosis, hypotension, arterial thrombosis, arterial embolism, aneurysm and arterial dissection, arterial rupture, speech disturbances, dyspnea, cough, pneumothorax, nausea, stomatitis, constipation, abdominal pain, dyspepsia, pancreatitis, gastroesophageal reflux disease, hemorrhoids, oral pain, dysphagia, dry mouth, flatulence, stomatitis, cholestatic hepatitis, rash, pruritus, hair loss, dry skin, hair color change, keratosis, erythema, cutaneous vasculitis, limb pain, back pain, arthralgia, muscle cramp, proteinuria, mucosal inflammation, asthenia, peripheral edema, fever, weight loss, elevated serum ALT, increased AST, elevated alkaline phosphatase in the blood, increased GGT, elevated creatinine in the blood, increased amylase, increased lipase, increased cholesterol in the blood, decreased white blood cell count, increased triglycerides in the blood, 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, nasal bleeding, pleural effusion, colitis, gastritis, oral pain, hemorrhoids, pruritus, psoriasis, urticaria, cutaneous vasculitis, arthritis, myopathy, renal failure, acute kidney injury, nephritis, fever, edema, chest pain, thrombocytopenia, depression, diabetes, decreased appetite, thyroid disorder, benign prostatic hyperplasia, eye edema, hip fracture, hematuria, chronic kidney disease, cerebral infarction, sensory disturbances, hepatic coma, oropharyngeal pain, hiccups, vesicles, eczema, skin erosion, skin desquamation, increased plasma thyroid-stimulating hormone, increased C-reactive protein, left ventricular dysfunction, benign thyroid neoplasm, hypertensive crisis, stomatitis, musculoskeletal pain, musculoskeletal chest pain, musculoskeletal discomfort, myalgia, neck pain, limb pain, spinal pain, thrombosis, hepatitis, biliary loss syndrome, musculoskeletal and connective tissue disorders, pain, chest pain, QT interval prolongation

This medication should be stored in a tightly closed container to prevent exposure to air or moisture. The recommended storage temperature is between 1 to 30 degrees Celsius at room temperature. This will help maintain the efficacy of the medication for a longer time.

Appearance

Yellow oval film-coated tablet

Package unit

30 tablets/bottle