tivozanib

Contraindicated in:

SBP >150 mmHg or DBP >100 mmHg;
History of symptomatic HF within preceding 6 mo;
Patients at risk of or with history of arterial thrombotic events, including MI, angina, or ischemic stroke within preceding 6 mo;
Significant bleeding within preceding 6 mo;
End-stage renal disease;
Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Hypertension (control before initiating therapy);
HF;
Patients at risk for or with history of venous thromboembolism;
Patients at risk for or with history of bleeding;
Surgery (interruption of therapy recommended);
Thyroid abnormalities;
Aspirin or tartrazine hypersensitivity;
Moderate hepatic impairment (↓ dose);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, DEEP VEIN THROMBOSIS, HF, HYPERTENSIVE CRISES, MI

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, GI fistula, GI PERFORATION, HEPATOBILIARY DISORDERS

GU: ↑serum creatinine, ↓fertility, acute kidney injury, proteinuria

Hemat: ↑activated partial thromboplastin time, ↑hemoglobin, anemia, bleeding, lymphopenia, thrombocytopenia

Metab: ↓appetite, ↓weight

MS: back pain, osteonecrosis

Neuro: fatigue, delirium, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), STROKE

Resp: cough, dysphonia, dyspnea, PULMONARY EMBOLISM, RESPIRATORY FAILURE

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.

Availability ⬆ ⬇

Capsules: 0.89 mg; 1.34 mg

Route/Dosage ⬆ ⬇

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 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 therapy); continue until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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 effects:

Decreased growth and spread of renal cell carcinoma.
Improvement in progression-free survival.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Extensively distributed to extravascular tissues.

Protein Binding: ≥99%.

Metabolism/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

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take as directed. If a dose is missed, omit and take next scheduled dose; do not double doses. Emphasize importance of regular lab tests to monitor for side effects.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
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; heavier than usual menstrual or vaginal bleeding; bruises that happen without a known cause or get larger; headaches; dizziness or weakness; severe or uncontrolled bleeding; 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.
Instruct patient to notify health care professional of medication regimen prior to treatment or surgery.
Rep: May cause fetal harm. Advise women of reproductive potential and men with female partners of reproductive potential to use effective contraception during therapy and for 1 mo after last dose. Advise patient to avoid breastfeeding during therapy and for 1 mo after last dose. Instruct patient to notify health care professional promptly if pregnancy is suspected. May impair female and male fertility.

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Indications ⬇

Contraind./Precautions ⬆ ⬇