Pronunciation:
tye-voe-za-nib
Trade Name(s)
Ther. Class.
Pharm. Class.
kinase inhibitors
Relapsed or refractory advanced renal cell carcinoma following ≥2 prior systemic therapies
Acts as a tyrosine kinase inhibitor of several vascular endothelial growth factor (VEGF) receptors, c-kit, and platelet-derived growth factor receptor. Overall effect is decreased angiogenesis, vascular permeability and growth of tumors.
Therapeutic Effect(s):
Absorption: Well absorbed following oral administration.
Distribution: Extensively distributed to extravascular tissues.
Protein Binding: ≥99%.
Metabolism and Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme. Primarily excreted in feces (26% as unchanged drug) with 12% being excreted in urine.
Half-life: 111 hr.
TIME/ACTION PROFILE (plasma concentrations)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
PO | unknown | 10 hr | 24 hr |
Contraindicated in:
Use Cautiously in:
CV: hypertension, DEEP VEIN THROMBOSIS, HF, HYPERTENSIVE CRISES, MYOCARDIAL INFARCTION
Derm: palmar-plantar erythrodysesthesia syndrome, rash, impaired wound healing
Endo: hyperglycemia, hypothyroidism, hyperthyroidism
F and E: hypercalcemia, hyperkalemia, hypomagnesemia, hyponatremia, hypophosphatemia
GI: ↑ amylase, ↑ lipase, ↑ liver enzymes, diarrhea, hyperbilirubinemia, nausea, stomatitis, vomiting
GU: ↑ serum creatinine, ↓ fertility, acute kidney injury, HEPATOBILIARY DISORDERS, proteinuria
Hemat: ↑ activated partial thromboplastin time, ↑ hemoglobin, anemia, BLEEDING, lymphocytopenia, thrombocytopenia, THROMBOEMBOLIC EVENTS
Metabolic: ↓ appetite, ↓ weight
MS: back pain, osteonecrosis
Neuro: delirium, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), STROKE
Resp: cough, dysphonia, dyspnea, PULMONARY EMBOLISM, RESPIRATORY FAILURE
Misc: fatigue
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
Strong CYP3A inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
PO (Adults): 1.34 mg once daily on Days 1–21 of a 28-day cycle (i.e. 21 days of tivozanib therapy, followed by 7 days off of therapy); continue until disease progression or unacceptable toxicity.
Hepatic Impairment
PO (Adults): Moderate hepatic impairment: 0.89 mg once daily on Days 1–21 of a 28-day cycle (i.e. 21 days of tivozanib therapy, followed by 7 days off of therapy); continue until disease progression or unacceptable toxicity.
Capsules: 0.89 mg, 1.34 mg
Ensure BP is controlled before starting therapy. Monitor BP after 2 wk and at least monthly thereafter during therapy. Treat with antihypertensive therapy when hypertension occurs. If Grade 3 hypertension occurs: hold for Grade 3 that persists despite optimal antihypertensive therapy. Resume at reduced dose when hypertension is controlled at ≤Grade 2. If Grade 4 hypertension occurs: permanently discontinue tivozanib. If tivozanib is held, monitor patients receiving antihypertensive therapy for hypotension.
Monitor for signs and symptoms of HF (dyspnea, swelling of ankles) during therapy. If Grade 3 HF occurs: hold tivozanib until improves to Grade 0–1 or baseline. Resume at reduced dose or discontinue depending on severity and persistence HF. If Grade 4 HF occurs: permanently discontinue tivozanib.
Monitor for signs and symptoms of cardiac ischemia or arterial thromboembolic events (new chest pain or pressure; numbness or weakness on one side of body; pain in your arms, back, neck or jaw; trouble talking; shortness of breath; sudden severe headache; vision changes; swelling in arms or legs) during therapy. If symptoms occur, permanently discontinue tivozanib.
Monitor patients who are at risk for or who have a history of bleeding during therapy. If Grade 3 or 4 bleeding occurs: discontinue tivozanib permanently.
Monitor for signs and symptoms of PRES (seizures, headaches, visual disturbances, confusion, altered mental function) during therapy. If symptoms occur, permanently discontinue therapy.
Lab Test Considerations:
Verify negative pregnancy test before starting therapy.
Advise patient to notify health care professional if signs and symptoms of hypertension or hypertensive crisis (confusion, headaches, dizziness, chest pain, shortness of breath), HF, heart attack or blood clots, bleeding problems (unusual bleeding from gums; red or black tarry stools, menstrual bleeding or vaginal bleeding that is heavier than normal; bruises that happen without a known cause or get larger; headaches; feeling dizzy or weak; bleeding that is severe or you cannot control; coughing up blood or blood clots; pink or brown urine; vomiting blood or vomit looks like "coffee grounds"; unexpected pain, swelling, or joint pain), PRES (headaches, seizures, confusion, blindness or change in vision, difficulty thinking) occur.