Drugs List

Therapeutic Indications

Uses

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.

Contraindications

Children under 18 years
Breastfeeding
Long QT syndrome
Pregnancy
Severe hepatic impairment
Torsade de pointes
Uncontrolled hypertension

Precautions and Warnings

Elderly
Family history of long QT syndrome
Females of childbearing potential
History of significant haemorrhage
Major surgery
Predisposition to gastrointestinal perforation
Predisposition to haemorrhage
Predisposition to thromboembolic disease
Severe trauma
Tobacco smoking
Behcet's disease
Cardiac failure
Cerebrovascular disorder
Diabetes mellitus
Electrolyte imbalance
Gastrointestinal fistula
Giant cell arteritis
History of aneurysm
History of thromboembolic disorder
History of thyroid disorder
History of torsade de pointes
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Marfan syndrome
Mild hepatic impairment
Occlusive peripheral arterial disease
Severe renal impairment
Takayasu arteritis
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

Pregnancy

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.

Lactation

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.

Side Effects

Abdominal distension
Abdominal pain
Acne
Alopecia
Anaemia
Angina pectoris
Anorexia
Arterial thrombosis
Arthralgia
Asthenia
Back pain
Chest pain
Chills
Constipation
Coronary artery disorder
Cough
Decreased appetite
Dermatitis
Diarrhoea
Dizziness
Dry mouth
Dry skin
Duodenal ulcer
Dysgeusia
Dyspepsia
Dysphagia
Dysphonia
Dyspnoea
Ear congestion
Elevated amylase levels
Elevated serum lipase
Elevated TSH
Epistaxis
Erythema
Fatigue
Flatulence
Flushing
Fungal infection
Gamma glutamyl transferase (GGT) increased
Gastroesophageal reflux disease
Gingivitis
Glossitis
Goitre
Haemorrhage
Headache
Hyperhidrosis
Hypertension
Hyperthyroidism
Hypothyroidism
Impaired memory
Impaired vision
Increase in alkaline phosphatase
Increase in haemoglobin
Increase in serum ALT/AST
Increased lacrimation
Insomnia
Mucosal inflammation
Muscle weakness
Musculoskeletal pain
Myalgia
Myocardial infarction
Myocardial ischaemia
Nasal congestion
Nausea
Pain
Palmar-plantar erythrodysaesthesia
Pancreatitis
Peripheral neuropathy
Peripheral oedema
Posterior reversible encephalopathy syndrome (PRES)
Prolongation of QT interval
Proteinuria
Pruritus
Pulmonary oedema
Pustular rash
Pyrexia
Rash
Rhinorrhoea
Serum creatinine increased
Skin exfoliation
Stomatitis
Tachycardia
Thrombocytopenia
Tinnitus
Transient ischaemic attack
Urticaria
Venous thrombosis
Vertigo
Vomiting
Weight loss
Xeroderma

Presentation

Oral formulations of tivozanib.

Drugs List

Therapeutic Indications

Uses

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.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Long QT syndrome
Pregnancy
Severe hepatic impairment
Torsade de pointes
Uncontrolled hypertension

Precautions and Warnings

Elderly
Family history of long QT syndrome
Females of childbearing potential
History of significant haemorrhage
Major surgery
Predisposition to gastrointestinal perforation
Predisposition to haemorrhage
Predisposition to thromboembolic disease
Severe trauma
Tobacco smoking
Behcet's disease
Cardiac failure
Cerebrovascular disorder
Diabetes mellitus
Electrolyte imbalance
Gastrointestinal fistula
Giant cell arteritis
History of aneurysm
History of thromboembolic disorder
History of thyroid disorder
History of torsade de pointes
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Marfan syndrome
Mild hepatic impairment
Occlusive peripheral arterial disease
Severe renal impairment
Takayasu arteritis
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

Pregnancy

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.

Lactation

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.

Side Effects

Abdominal distension
Abdominal pain
Acne
Alopecia
Anaemia
Angina pectoris
Anorexia
Arterial thrombosis
Arthralgia
Asthenia
Back pain
Chest pain
Chills
Constipation
Coronary artery disorder
Cough
Decreased appetite
Dermatitis
Diarrhoea
Dizziness
Dry mouth
Dry skin
Duodenal ulcer
Dysgeusia
Dyspepsia
Dysphagia
Dysphonia
Dyspnoea
Ear congestion
Elevated amylase levels
Elevated serum lipase
Elevated TSH
Epistaxis
Erythema
Fatigue
Flatulence
Flushing
Fungal infection
Gamma glutamyl transferase (GGT) increased
Gastroesophageal reflux disease
Gingivitis
Glossitis
Goitre
Haemorrhage
Headache
Hyperhidrosis
Hypertension
Hyperthyroidism
Hypothyroidism
Impaired memory
Impaired vision
Increase in alkaline phosphatase
Increase in haemoglobin
Increase in serum ALT/AST
Increased lacrimation
Insomnia
Mucosal inflammation
Muscle weakness
Musculoskeletal pain
Myalgia
Myocardial infarction
Myocardial ischaemia
Nasal congestion
Nausea
Pain
Palmar-plantar erythrodysaesthesia
Pancreatitis
Peripheral neuropathy
Peripheral oedema
Posterior reversible encephalopathy syndrome (PRES)
Prolongation of QT interval
Proteinuria
Pruritus
Pulmonary oedema
Pustular rash
Pyrexia
Rash
Rhinorrhoea
Serum creatinine increased
Skin exfoliation
Stomatitis
Tachycardia
Thrombocytopenia
Tinnitus
Transient ischaemic attack
Urticaria
Venous thrombosis
Vertigo
Vomiting
Weight loss
Xeroderma

Overdosage

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 ).

Further Information

Last Full Review Date: November 2020

Reference Sources

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.