Tivozanib (Fotivda) is a kinase inhibitor clinically used for the treatment of relapsed or refractory advanced renal cell carcinoma (RCC) after two or more lines of systemic therapy. It provides an important treatment option for patients with advanced renal cell carcinoma. Like other targeted drugs, tivozanib may be accompanied by a series of adverse reactions while exerting its anti-tumor effect.

Side Effects of Tivozanib (Fotivda)

Systemic Adverse Reactions

Fatigue is one of the most common side effects, with an incidence rate as high as 67% in clinical studies, of which 13% is severe fatigue of Grade 3 or 4.

It is one of the main factors affecting patients’ quality of life and requires full attention during the treatment process.

Cardiovascular System Effects

Hypertension is an adverse reaction that deserves special attention for this drug, with an incidence rate of 44%, of which 24% reaches the severe level of Grade 3.

The median time to onset of hypertension is 2 weeks after the start of treatment, but it may occur at any time during treatment (range: 0–192 weeks).

Digestive System Reactions

The incidence rates are 43% for diarrhea, 30% for nausea, 21% for stomatitis, and 18% for vomiting.

These gastrointestinal symptoms are usually more obvious in the early stage of medication, and most patients can be relieved through symptomatic treatment.

Effects on Other Systems

The incidence rate is 27% for dysphonia (hoarseness), 22% for cough, and 15% for dyspnea.

The incidence rate of hypothyroidism is 24%, and regular monitoring of thyroid function is required.

Severe Side Effects of Tivozanib (Fotivda)

Risk of Hypertensive Crisis

Tivozanib may cause severe hypertension and hypertensive crisis. Although the incidence rate is low (0.8%), it may be life-threatening.

There have been cases where patients died of hypertensive emergency after drug overdose.

Blood pressure must be controlled before starting treatment, and blood pressure should be monitored every 2 weeks and at least once a month during treatment. Once uncontrolled hypertension or hypertensive crisis occurs, the drug must be discontinued immediately and active intervention should be taken.

Cardiotoxic Reactions

Although the incidence rate of heart failure is not high (1.6%), 1% of cases reach the severe level of Grade 3, and 0.6% are fatal events.

For patients with a history of symptomatic heart failure, the use of this drug requires special caution.

Tivozanib (Fotivda) Use in Special Populations

Patients with Hepatic Impairment

For patients with moderate hepatic impairment (total bilirubin > 1.5–3 times the upper limit of normal), the dose needs to be reduced to 0.89 mg.

Patients with severe hepatic impairment should avoid using this drug.

Women of Childbearing Age and Pregnant Women

Tivozanib may cause harm to the fetus and has embryo-fetal toxicity.

Women of childbearing age should take effective contraceptive measures during treatment and for 1 month after the last dose.

Lactating women should also stop breastfeeding during treatment.

Management of Surgical Patients

Since the drug may affect wound healing, it should be discontinued for at least 24 days before elective surgery. The drug can be resumed only after at least 2 weeks after major surgery and when the wound is completely healed.