- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of tivozanib.
Advanced renal cell carcinoma
First line treatment of advanced renal cell carcinoma in adults.
Treatment of advanced renal cell carcinoma in adults, who are VEGFR and mTOR pathway inhibitor-naive following disease progression after one treatment with cytokine therapy.
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
28 day cycle: 1340micrograms once daily for 21 days, then 7 days without treatment.
Patients with Hepatic Impairment
Mild hepatic impairment: No dose reduction needed.
Moderate hepatic impairment: Reduce dose to 1340micrograms every other day.
Severe hepatic impairment: Contraindicated.
Additional Dosage Information
If a dose is missed or vomited, the patient should not be given an additional dose. The usual prescribed dose should be taken at the next scheduled time.
Grade 4 events: May require treatment to be temporarily interrupted.
Grade 3 events: Reduce dose to 890micrograms once daily for 21 days, then 7 days without treatment.
Grade 2 proteinuria (greater than 1.0g to 3.4g per 24 hours) or Grade 3 proteinuria (equal to or greater than 3.5g per 24 hours): Interrupt or reduce the dose.
Persistent hypertension (despite anti-hypertensive therapy): Reduce dose. Alternatively, interrupt treatment until blood pressure is controlled, then resume at a lower dose.
Children under 18 years
Long QT syndrome
Severe hepatic impairment
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
Females of childbearing potential
History of significant haemorrhage
Predisposition to gastrointestinal perforation
Predisposition to haemorrhage
Predisposition to thromboembolic disease
Giant cell arteritis
History of aneurysm
History of thromboembolic disorder
History of thyroid disorder
History of torsade de pointes
Ischaemic heart disease
Mild hepatic impairment
Occlusive peripheral arterial disease
Severe renal impairment
Vascular Ehlers-Danlos syndrome
Correct electrolyte disorders before treatment
Reduce dose in patients with moderate hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Ensure hypertension is controlled prior to treatment
Treatment to be prescribed under the supervision of a specialist
Contains tartrazine- risk of allergic reactions
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor for proteinuria before and periodically during treatment
Monitor hepatic function before treatment and regularly during treatment
Monitor thyroid function prior to and periodically during treatment
Screen patient for hypertension and control as appropriate
Monitor ECG in patients at risk of QT prolongation
Monitor for symptoms of gastrointestinal perforation or fistula
Monitor patients for signs and symptoms of cardiac failure
Monitor serum electrolytes
Advise patient to report headaches, seizures, confusion, visual disturbance
Consider discontinuing therapy if significant cardiac failure develops
Consider dose reduction if cardiac failure occurs
Treatment may adversely affect wound healing
Discontinue before elective surgery: impairs wound healing
Discontinue if Grade 4 proteinuria occurs (Nephrotic syndrome)
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Interrupt therapy/reduce dose if palmar-plantar erythrodysaesthesia occurs
Suspend treatment and/or reduce dose if grade 2 or 3 proteinuria
Suspend treatment in severe hypertension that cannot be controlled
Suspend treatment if bleeding requiring medical treatment occurs
Advise patient not to take St John's wort concurrently
Male & female: May cause infertility
Female: Effect of hormonal contraceptive may be reduced
Female: Use barrier contraception during and for 1 month after treatment
Male: Use barrier contraception during and for 1 month after treatment
Advise patient on giving up smoking
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.
Risk factors for aneurysm and artery dissection
Use of systemic VEGF inhibitors may promote the formation of aneurysms or artery dissections, mainly in relation to aortic aneurysm rupture and aortic dissection. It is therefore important to consider the risk of aneurysm and artery dissection in patients with risk factors such as hypertension, history of aneurysm, smoking, diabetes, coronary, cerebrovascular or peripheral arterial disease, and hyperlipidaemia. Other risk factors include Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, and the use of fluoroquinolones. In patients receiving VEGF inhibitors, any modifiable risk factors such as smoking and hypertension should be reduced as far as possible.
Pregnancy and Lactation
Tivozanib is contraindicated during pregnancy.
The manufacturer recommends tivozanib should not be used during pregnancy. If the patient becomes pregnant while taking tivozanib, the hazard to the foetus requires discussion. Animal studies have shown reproductive toxicity. There are no adequate data available on the use of tivozanib in human pregnancy.
Tivozanib is contraindicated during breastfeeding.
The manufacturer recommends women should not breastfeed during treatment with tivozanib. It is not known whether tivozanib is excreted in human milk. There is potential for serious side effects in the nursing infant.
Coronary artery disorder
Elevated amylase levels
Elevated serum lipase
Gamma glutamyl transferase (GGT) increased
Gastroesophageal reflux disease
Increase in alkaline phosphatase
Increase in haemoglobin
Increase in serum ALT/AST
Posterior reversible encephalopathy syndrome (PRES)
Prolongation of QT interval
Serum creatinine increased
Transient ischaemic attack
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: November 2020
MHRA Drug Safety Update July 2020
Available at: https://www.gov.uk/drug-safety-update/systemically-administered-vegf-pathway-inhibitors-risk-of-aneurysm-and-artery-dissection
Last accessed: 17 December 2020
Summary of Product Characteristics: Fotivda 890mcg hard capsules. EUSA Pharma (UK) Limited. Revised September 2019.
Summary of Product Characteristics: Fotivda 1340mcg hard capsules. EUSA Pharma (UK) Limited. Revised September 2019.
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.