CNS: dizziness, fatigue, headache, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES).
CV: hypertension, THROMBOTIC EVENTS.
Derm: dry skin, hair color changes, palmar-plantar erythrodysesthesia, rash, impaired wound healing.
Endo: hypothyroidism, ADRENAL INSUFFICIENCY (IN COMBINATION WITH NIVOLUMAB).
F and E: hypocalcemia, hypophosphatemia, hypokalemia, hypomagnesemia, hyponatremia.
GI: abdominal pain, altered taste, ↓appetite, constipation, diarrhea, dyspepsia, hepatotoxicity (in combination with nivolumab), ↑liver enzymes, nausea, oral pain, stomatitis, vomiting, weight loss, GASTROINTESTINAL PERFORATION/FISTULA.
GU: proteinuria, infertility, nephrotic syndrome.
Hemat: lymphocytopenia, neutropenia, thrombocytopenia, anemia, BLEEDING.
MS: arthralgia, muscle spasms, osteonecrosis of the jaw.
Resp: cough, dyspnea.
Capsules and tablets are not interchangeable
Cabometyx
Advanced Renal Cell Carcinoma
- PO (Adults): As monotherapy 60 mg once daily until disease progression or unacceptable toxicity. With nivolumab 40 mg once daily until disease progression or unacceptable toxicity.Concurrent use of strong CYP3A4 inhibitor (as monotherapy) 40 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inhibitor). Concurrent use of strong CYP3A4 inhibitor (with nivolumab) 20 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inhibitor). Concurrent use of strong CYP3A4 inducer (as monotherapy) 80 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inducer). Concurrent use of strong CYP3A4 inducer (with nivolumab) 60 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inducer).
Hepatic Impairment
- PO (Adults): Moderate hepatic impairment 40 mg once daily until disease progression or unacceptable toxicity.
Hepatocellular Carcinoma- PO (Adults): 60 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor 40 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inhibitor). Concurrent use of strong CYP3A4 inducer 80 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inducer).
Hepatic Impairment
- PO (Adults): Moderate hepatic impairment 40 mg once daily until disease progression or unacceptable toxicity.
Differentiated Thyroid Cancer- PO (Adults and Children 12 yr and body surface area [BSA] 1.2 m2): 60 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor 40 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inhibitor). Concurrent use of strong CYP3A4 inducer 80 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inducer).
- PO (Adults and Children 12 yr and body surface area [BSA] <1.2 m2): 40 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor 20 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inhibitor). Concurrent use of strong CYP3A4 inducer 60 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inducer).
Hepatic Impairment
- PO (Adults and Children 12 yr and body surface area [BSA] 1.2 m2): 40 mg once daily until disease progression or unacceptable toxicity.
Hepatic Impairment
- PO (Adults and Children 12 yr and body surface area [BSA] <1.2 m2): 20 mg once daily until disease progression or unacceptable toxicity.
Cometriq
- PO (Adults): 140 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor 100 mg once daily until disease progression or unacceptable toxicity (resume full dose 4 days after discontinuing inhibitor). Concurrent use of strong CYP3A4 inducer 180 mg once daily until disease progression or unacceptable toxicity (resume full dose 23 days after discontinuing inducer).
Hepatic Impairment
- PO (Adults): Mild or moderate hepatic impairment 80 mg once daily.
Therapeutic Classification: antineoplastics
Pharmacologic Classification: kinase inhibitors
Absorption: Well absorbed following oral administration; food significantly enhances absorption.
Distribution: Extensively distributed to tissues.
Protein Binding: >99.7%.
Metabolism/Excretion: Highly metabolized by the liver, mostly by the CYP3A4 isoenzyme. 54% excreted in feces, 27% in urine (as metabolites).
Half-life: 55 hr (Cometriq); 99 hr (Cabometyx).