CV: hypertension, QT interval prolongation, HF, hypotension, MI.
Derm: alopecia, palmar-plantar erythrodysesthesia syndrome, rash, hyperkeratosis, impaired wound healing.
EENT: dysphonia, epistaxis.
Endo: hypothyroidism.
F and E: dehydration, hypocalcemia, hypokalemia.
GI: ↓ appetite, abdominal pain, diarrhea, dry mouth, nausea, stomatitis, vomiting, ↑ liver enzymes, GI PERFORATION/FISTULA FORMATION, HEPATOTOXICITY.
GU: proteinuria, renal impairment, ↓ fertility, NEPHROTIC SYNDROME.
Hemat: bleeding, thrombocytopenia.
Metab: ↓ weight.
MS: arthralgia/myalgia, osteonecrosis (primarily of jaw).
Neuro: dysgeusia, fatigue, headache, insomnia, CAROTID ARTERY HEMORRHAGE, REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME (RPLS), STROKE.
Resp: cough.
Differentiated Thyroid Cancer
- PO (Adults): 24 mg once daily until disease progression or unacceptable toxicity.
Renal Impairment
- PO (Adults): CCr <30 mL/min: 14 mg once daily until disease progression or unacceptable toxicity.
Hepatic Impairment
- PO (Adults): Severe hepatic impairment: 14 mg once daily until disease progression or unacceptable toxicity.
Renal Cell Carcinoma
- PO (Adults): First-line treatment of advanced renal cell carcinoma: 20 mg once daily (in combination with pembrolizumab) until disease progression or unacceptable toxicity or up to 2 yr. After 2 yr of combination therapy, continue 20 mg once daily (as monotherapy) until disease progression or unacceptable toxicity. Previously treated renal cell carcinoma: 18 mg once daily until disease progression or unacceptable toxicity.
Renal Impairment
- PO (Adults): CCr <30 mL/min: First-line treatment of advanced renal cell carcinoma: 10 mg once daily (in combination with pembrolizumab) until disease progression or unacceptable toxicity or up to 2 yr. After 2 yr of combination therapy, continue 10 mg once daily (as monotherapy) until disease progression or unacceptable toxicity. Previously treated renal cell carcinoma: 10 mg once daily until disease progression or unacceptable toxicity.
Hepatic Impairment
- PO (Adults): Severe hepatic impairment: 10 mg once daily until disease progression or unacceptable toxicity.
Hepatocellular Carcinoma
- PO (Adults ≥60 kg): 12 mg once daily until disease progression or unacceptable toxicity.
- PO (Adults <60 kg): 8 mg once daily until disease progression or unacceptable toxicity.
Endometrial Carcinoma
- PO (Adults): 20 mg once daily until disease progression or unacceptable toxicity.
Renal Impairment
- PO (Adults): CCr <30 mL/min: 10 mg once daily until disease progression or unacceptable toxicity.
Hepatic Impairment
- PO (Adults): Severe hepatic impairment: 10 mg once daily until disease progression or unacceptable toxicity.
Therapeutic Classification: antineoplastics
Pharmacologic Classification: kinase inhibitors
Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: 98–99%.
Metabolism/Excretion: Metabolized primarily by the CYP3A isoenzyme and aldehyde oxidase; 64% eliminated in feces, 25% in urine.
Half-life: 28 hr.
(improvement in progression-free survival)