Tivozanib

Tivozanib is a tyrosine kinase inhibitor. In vitro cellular kinase assays demonstrated that tivozanib inhibits phosphorylation of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3 and inhibits other kinases including c-kit and PDGFR β at clinically relevant concentrations.

• FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

• None. None.contraindicated

Recommended Dose: 1.34 mg once daily with or without food for 21 days on treatment followed by 7 days off treatment (28-day cycle) until disease progression or unacceptable toxicity. ( 2.1 ) Dose interruptions and/or dose reduction may be needed to manage adverse reactions. ( 2.2 ) For patients with moderate hepatic impairment, reduce the dose to 0.89 mg for 21 days on treatment followed by 7 days off treatment (28-day cycle). ( 2.3 ) 2.1 Recommended Dosing The recommended dosage of FOTIVDA is 1.34 mg taken orally once daily for 21 days on treatment followed by 7 days off treatment for a 28-day cycle. Continue treatment until disease progression or until unacceptable toxicity occurs. Take FOTIVDA with or without food. Swallow the FOTIVDA capsule whole with a glass of water. Do not open the capsule. If a dose is missed, the next dose should be taken at the next scheduled time. Do not take two doses at the same time. 2.2 Dose Modifications for Adverse Reactions Initiate medical management for diarrhea, nausea, or vomiting prior to dose interruption or reduction. If dose modifications are required for adverse reactions, reduce the dosage of FOTIVDA to 0.89 mg for 21 days on treatment followed by 7 days off treatment for a 28-day cycle. Recommendations for dosage modifications are provided in Table 1 . Table 1. Dosage Modifications for Adverse Reactions Adverse Reaction Severity Grades are based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose. ( 5.1 ) Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA. ( 5.2 ) Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke. ( 5.3 ) Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events. ( 5.4 ) Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding. ( 5.5 ) Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA. ( 5.6 ) Perforations and Fistulas: Monitor for symptoms. Discontinue FOTIVDA for severe or life-threatening gastrointestinal perforation. ( 5.7 ) Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA. ( 5.8 ) Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

The following clinically significant adverse reactions are also described elsewhere in the labeling: Hypertension and Hypertensive Crisis [see WARNINGS AND PRECAUTIONS (5.1) ] Cardiac Failure [see WARNINGS AND PRECAUTIONS (5.2) ] Cardiac Ischemia and Arterial Thromboembolic Events [see WARNINGS AND PRECAUTIONS (5.3) ] Venous Thromboembolic Events [see WARNINGS AND PRECAUTIONS (5.4) ] Hemorrhagic Events [see WARNINGS AND PRECAUTIONS (5.5) ] Proteinuria [see WARNINGS AND PRECAUTIONS (5.6) ] Gastrointestinal Perforation and Fistula Formation [see WARNINGS AND PRECAUTIONS (5.7) ] Thyroid Dysfunction [see WARNINGS AND PRECAUTIONS (5.8) ] Risk of Impaired Wound Healing [see WARNINGS AND PRECAUTIONS (5.9) ] Reversible Posterior Leukoencephalopathy Syndrome (RPLS) [see WARNINGS AND PRECAUTIONS (5.10) ] The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Lactation: Advise not to breastfeed. ( 8.2 ) Females and Males of Reproductive Potential: Can impair fertility. ( 8.3 ) Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment. ( 2.3 , 8.7 ) 8.1 Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action, FOTIVDA can cause fetal harm when administered to a pregnant woman [see CLINICAL PHARMACOLOGY (12.1) ] . There are no available data on FOTIVDA use in pregnant woman to inform the drug-associated risk. In embryo-fetal developmental studies, oral administration of tivozanib to pregnant animals during the period of organogenesis caused maternal toxicity, fetal malformations and embryo- fetal death at doses below the maximum recommended clinical dose on a mg/m 2 basis [see DATA ] . Advise pregnant woman of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically-recognized pregnancies is 2% to 4% and 15% to 20% respectively.

Metabolism

The pharmacokinetics of tivozanib were evaluated in patients with solid tumors administered 1.34 mg once daily unless otherwise specified. Steady-state tivozanib AUC and C max increased in a dose-proportional manner over the dose range of 0.89 to 1.78 mg once daily (0.67 to 1.3 times the recommended dose).

Overdosage with FOTIVDA can cause severe hypertension and hypertensive crisis that may result in death [see WARNINGS AND PRECAUTIONS (5.1) ] . During clinical studies, three patients inadvertently received doses ≥ 2.68 mg (≥ 2 times the recommended dose) of FOTIVDA. One patient who received two daily doses of 8.9 mg of FOTIVDA experienced hypertensive crisis with severe hypertensive retinopathy; a second patient who received three doses of 1.34 mg in one day experienced fatal uncontrolled hypertension; and a third patient who received two doses of 1.34 mg FOTIVDA in one day experienced persistent hypertension lasting over 5 days. There is no specific treatment or antidote for FOTIVDA overdose. In cases of suspected overdose, withhold FOTIVDA, closely monitor patients for hypertension and hypertensive crisis and other potential adverse reactions. Immediately manage signs or symptoms of hypertension and provide other supportive care as clinically indicated.

• Mar 10, 2021NDANDA212904Aveo Pharms

1. 1Fatigue30620%
2. 2Diarrhoea19213%
3. 3Blood Pressure Increased1489.7%
4. 4Nausea1378.9%
5. 5Disease Progression1348.7%
6. 6Decreased Appetite1328.6%
7. 7Dysphonia1107.2%
8. 8Death996.5%
9. 9Asthenia905.9%
10. 10Off Label Use845.5%
11. 11Hypertension754.9%
12. 12Vomiting704.6%
13. 13Pain694.5%
14. 14Dyspnoea674.4%
15. 15Constipation543.5%

The 10 most recently updated of 43 ClinicalTrials.gov registrations naming Tivozanib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Evaluating Efficacy of Tivozanib (AV-951) in Biliary Tract Cancers
  Recruiting · Phase 1 · Phase 2 · Interventional · 31 enrolled · National Cancer Institute (NCI)
  NCT04645160updated 2026-06-05
• Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types
  Recruiting · Phase 1 · Phase 2 · Interventional · 29 enrolled · University of Florida
  NCT05000294updated 2026-06-05
• Testing the Addition of the Anti-Cancer Drug Tivozanib to Immunotherapy (Pembrolizumab) After Surgery to Remove All Known Sites of Kidney Cancer
  Recruiting · Phase 3 · Interventional · 1,040 enrolled · Alliance for Clinical Trials in Oncology
  NCT06661720updated 2026-06-02
• Tivozanib + Enzalutamide in Adv Prostate Cancer
  Terminated · Phase 2 · Interventional · 5 enrolled · Massachusetts General Hospital
  NCT01885949updated 2026-05-20
• Phase 2 Study of Combination Tivozanib and Nivolumab in Advanced Non-Clear Cell Renal Cell Carcinoma
  Recruiting · Phase 2 · Interventional · 48 enrolled · M.D. Anderson Cancer Center
  NCT06053658updated 2026-05-20
• Drug Screening Using Novel IMD in Renal Cell Carcinoma
  Recruiting · Phase 1 · Interventional · 20 enrolled · Oliver Jonas
  NCT05700461updated 2026-05-18
• Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma
  Completed · Phase 3 · Interventional · 343 enrolled · AVEO Pharmaceuticals, Inc.
  NCT04987203updated 2026-05-08
• TDM for Optimized Outcome in Patients With mRCC.
  Recruiting · Observational · 200 enrolled · Niels Fristrup
  NCT04659343updated 2026-05-04
• Real World Evidence of Tivozanib as First-line Treatment for Metastatic Clear Cell Renal Cell Carcinoma
  Completed · Observational · 200 enrolled · Spanish Oncology Genito-Urinary Group
  NCT07354282updated 2026-01-21
• RP2 and Tivozanib for the Treatment of Metastatic Renal Cell Cancer After Progression on Immunotherapy
  Not yet recruiting · Phase 2 · Interventional · 35 enrolled · City of Hope Medical Center
  NCT07218692updated 2025-10-20

Frequently asked questions

How does Tivozanib work?

Tivozanib is a tyrosine kinase inhibitor. In vitro cellular kinase assays demonstrated that tivozanib inhibits phosphorylation of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3 and inhibits other kinases including c-kit and PDGFR β at clinically relevant concentrations.

What is Tivozanib used for?

According to FDA labeling, Tivozanib carries indications including: FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tivozanib?

Tivozanib is classified as Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors, Kinase Inhibitor, Receptor Tyrosine Kinase Inhibitors, Tyrosine Kinase Inhibitors.

What are the brand names for Tivozanib?

Tivozanib is marketed under brand names including Fotivda.

What are the contraindications for Tivozanib?

Tivozanib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.