tivozanib hydrochloride monohydrate: clinical use

Prescribing considerations

• Initiation and supervision require experience with anticancer therapies.
• Control hypertension before treatment and reassess cardiovascular, thrombotic, bleeding and aneurysm risks.
• Use caution in severe renal impairment or dialysis because experience is limited.
• Use caution and monitor tolerability in hepatic impairment; the product is not recommended in severe hepatic impairment.
• Plan interruption around major surgery and restart only after adequate wound healing.
• Discuss contraception and possible effects on male and female fertility.

Contraindications and cautions

• Hypersensitivity to tivozanib or a formulation excipient.
• Concurrent herbal preparations containing St John’s wort.

Monitoring

• Blood pressure before and throughout treatment.
• Urinary protein before treatment and periodically thereafter.
• ALT, AST, bilirubin and alkaline phosphatase before and during treatment.
• Thyroid function before and periodically during treatment.
• ECG and calcium, magnesium and potassium in patients at risk of QT prolongation.
• Clinical features of cardiac failure, thrombosis, haemorrhage, PRES, gastrointestinal perforation or fistula, and impaired wound healing.

Clinical pharmacology

Tivozanib selectively inhibits VEGFR-1, VEGFR-2 and VEGFR-3. It is more than 99% protein-bound and has a mean terminal half-life of approximately 4.5–5.1 days. Faecal elimination predominates; unchanged tivozanib has not been detected in urine. CYP3A4 and CYP1A1 can metabolise it, although unchanged tivozanib is the main circulating form.

Formulation and product differences

• The selected formulation is a hard gelatin capsule containing mannitol and magnesium stearate; it must not be opened.
• A lower-strength capsule is also marketed for treatment modification and differs in appearance and excipients; unlike the selected capsule, it contains tartrazine in the printing ink.

Capsule

Route: Oral

Strengths: 890 micrograms, 1340 micrograms