BOMETYX at a reduced dose. Dose modification due to diarrhea occurred in 26% of patients.
5.6 Palmar-Plantar Erythrodysesthesia Syndrome
Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 42% of patients treated with CABOMETYX and in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2% of CABOMETYX-treated patients and in <1% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to PPES occurred in 16% of patients.
5.7 Reversible Posterior Leukoencephalopathy Syndrome
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an eva luation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
5.8 Embryo-fetal Toxicity
Based on data from animal studies and its mechanism of action, CABOMETYX can cause fetal harm when administered to a pregnant woman. Cabozantinib administration to pregnant animals during organogenesis resulted in embryolethality at exposures below those occurring clinically at the recommended dose, and in increased incidences of skeletal variations in rats and visceral variations and malformations in rabbits. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose [See USE IN SPECIFIC POPULATIONS (8.1), (8.3), and CLINICAL PHARMACOLOGY (12.1)].
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the label:
Hemorrhage [see WARNINGS AND PRECAUTIONS (5.1)]
GI Perforations and Fistulas [see WARNINGS AND PRECAUTIONS (5.2)]
Thrombotic Events [see WARNINGS AND PRECAUTIONS (5.3)]
Hypertension and Hypertensive Crisis [see WARNINGS AND PRECAUTIONS (5.4)]
Diarrhea [see WARNINGS AND PRECAUTIONS (5.5)]
Palmar-plantar erythrodysesthesia syndrome [see WARNINGS AND PRECAUTIONS (5.6)]
Reversible Posterior Leukoencephalopathy Syndrome [see WARNINGS AND PRECAUTIONS (5.7)]
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of CABOMETYX was eva luated in Study 1, a randomized, open-label trial in which 331 patients with advanced renal cell carcinoma received 60 mg CABOMETYX and 322 patients received 10 mg everolimus administered daily until disease progression or unacceptable toxicity. Patients on both arms who had disease progression could continue treatment at the discretion of the investigator [see CLINICAL STUDIES (14)]. The median duration of treatment was 7.6 months (range 0.3 – 20.5) for patients receiving CABOMETYX and 4.4 months (range 0.21 – 18.9) for patients receiving everolimus.
Adverse reactions which occurred in ≥ 25% of CABOMETYX-treated patients included, in order of decreasing frequency: diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (PPES), hypertension, |
