FOTIVDA

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). Steady-state was reached by 14 days and the accumulation ratio after administration of 1.34 mg once daily was approximately 6- to 7- fold. Mean steady-state tivozanib [coefficient of variation...

The efficacy of FOTIVDA was evaluated in TIVO-3 (NCT02627963), a randomized (1:1), open- label, multicenter trial of FOTIVDA versus sorafenib in patients with relapsed or refractory advanced RCC who received 2 or 3 prior systemic treatments including at least one VEGFR kinase inhibitor other than sorafenib or tivozanib. Patients were randomized to receive FOTIVDA 1.34 mg orally once daily for 21 days on treatment followed by 7 days off treatment for a 28-day cycle, or to receive sorafenib 400 mg orally twice a day continuously, until disease progression or unacceptable toxicity. Randomization ...

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) ] Gastro...

None. None. ( 4 )

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 FO...

7 DRUG INTERACTIONS CYP3A Inducers: Avoid concomitant use of strong CYP3A inducers. ( 7.1 ) 7.1 Effect of Other Drugs on FOTIVDA Strong CYP3A Inducers Concomitant use of FOTIVDA with a strong CYP3A inducer decreases tivozanib exposure [see CLINICAL PHARMACOLOGY (12.3) ], which may reduce FOTIVDA anti-tumor activity. Avoid concomitant use of strong CYP3A inducers with FOTIVDA.