METYX is not recommended for use in patients with severe hepatic impairment [see USE IN SPECIFIC POPULATIONS (8.6), CLINICAL PHARMACOLOGY (12.3)].
3 DOSAGE FORMS AND STRENGTHS
60 mg CABOMETYX tablets are yellow film-coated, oval shaped with no score, and debossed with "XL" on one side and "60" on the other side.
40 mg CABOMETYX tablets are yellow film-coated, triangle shaped with no score, and debossed with "XL" on one side and "40" on the other side.
20 mg CABOMETYX tablets are yellow film-coated, round with no score, and debossed with "XL" on one side and "20" on the other side.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Hemorrhage
Severe hemorrhage occurred with CABOMETYX. The incidence of Grade ≥ 3 hemorrhagic events was 2.1% in CABOMETYX-treated patients and 1.6% in everolimus-treated patients. Fatal hemorrhages also occurred in the cabozantinib clinical program.
Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
5.2 GI Perforations and Fistulas
In a randomized study in renal cell carcinoma, fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of everolimus-treated patients. Gastrointestinal (GI) perforations were reported in 0.9% of CABOMETYX-treated patients and 0.6% of everolimus-treated patients. Fatal perforations occurred in the cabozantinib clinical program.
Monitor patients for symptoms of fistulas and perforations. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
5.3 Thrombotic Events
CABOMETYX treatment results in an increased incidence of thrombotic events. Venous thromboembolism was reported in 7.3% of CABOMETYX-treated patients and 2.5% of everolimus-treated patients. Pulmonary embolism occurred in 3.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Events of arterial thromboembolism were reported in 0.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program.
Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
5.4 Hypertension and Hypertensive Crisis
CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension. Hypertension was reported in 37% (15% Grade ≥ 3) of CABOMETYX-treated patients and 7.1% (3.1% Grade ≥ 3) of everolimus-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
5.5 Diarrhea
Diarrhea occurred in 74% of patients treated with CABOMETYX and in 28% of patients treated with everolimus. Grade 3 diarrhea occurred in 11% of CABOMETYX-treated patients and in 2% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CA |
