Drugs List

Therapeutic Indications

Uses

Advanced renal cell carcinoma

Treatment of advanced renal cell carcinoma after failure of prior treatment with sunitinib or a cytokine.

Contraindications

Children under 18 years
Brain neoplasm
Breastfeeding
Galactosaemia
Gastrointestinal haemorrhage
Pregnancy
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Uncontrolled hypertension

Precautions and Warnings

Predisposition to thromboembolic disease
Tobacco smoking
Arterial aneurysm
Behcet's disease
Cerebrovascular accident
Cerebrovascular disorder
Deep vein thrombosis
Diabetes mellitus
Giant cell arteritis
Glucose-galactose malabsorption syndrome
Hepatic impairment - Child-Pugh score between 7 and 9
History of aneurysm
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Lactose intolerance
Marfan syndrome
Myocardial infarction
Occlusive peripheral arterial disease
Pulmonary embolism
Renal impairment - creatinine clearance below 15ml/minute
Retinal blood vessel occlusion
Takayasu arteritis
Thromboembolic disorder
Transient ischaemic attack
Vascular Ehlers-Danlos syndrome

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 initiated and supervised by a specialist
Contains lactose
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 haemoglobin prior to initiating therapy and periodically thereafter
Monitor hepatic function before treatment and regularly during treatment
Monitor thyroid function prior to and periodically during treatment
Monitor blood pressure regularly
Monitor for symptoms of gastrointestinal perforation or fistula
Monitor haematocrit values
Monitor patients for signs and symptoms of cardiac failure
Advise patient to report headaches, seizures, confusion, visual disturbance
Consider discontinuing therapy if significant cardiac failure develops
Consider dose reduction if cardiac failure occurs
Reduce dose if hypertension cannot be controlled
Discontinue treatment 24 hours prior to surgery
Discontinue if nephrotic syndrome occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if significant proteinuria occurs, treat and restart therapy
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
Advise patient grapefruit products may increase plasma level
May cause impaired fertility
Female: Contraception required during and for 1 week 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

Axitinib is contraindicated for use during pregnancy.

Animal studies have shown reproductive toxicity including malformations.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Axitinib is contraindicated in breastfeeding.

It is unknown whether axitinib is excreted in human milk but a risk to the nursing infant cannot be excluded.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Alopecia
Anaemia
Aneurysm
Artery dissection
Arthralgia
Asthenia
Cardiac failure
Cardiopulmonary failure
Cholecystitis
Congestive cardiac failure
Constipation
Cough
Decreased appetite
Decreased ejection fraction
Dehydration
Diarrhoea
Dizziness
Dry skin
Dysgeusia
Dyspepsia
Dysphonia
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Elevated TSH
Erythema
Extremity pain
Fatigue
Flatulence
Gastro-intestinal fistulae
Gastro-intestinal perforation
Glossodynia
Haemorrhage
Haemorrhoids
Headache
Hyperbilirubinaemia
Hypercalcaemia
Hyperkalaemia
Hypertension
Hypertensive crisis
Hyperthyroidism
Hypothyroidism
Increase in alkaline phosphatase
Increase in creatinine
Increase in serum ALT/AST
Leukopenia
Mucosal inflammation
Myalgia
Nausea
Neutropenia
Oropharyngeal pain
Palmar-Plantar Erythrodysaesthesia syndrome
Polycythaemia
Posterior reversible encephalopathy syndrome (PRES)
Proteinuria
Pruritus
Rash
Renal failure
Serum bilirubin increased
Stomatitis
Thrombocytopenia
Thromboembolic disorders
Tinnitus
Upper abdominal pain
Ventricular dysfunction
Vomiting
Weight loss

Presentation

Tablets containing axitinib.

Drugs List

Therapeutic Indications

Uses

Advanced renal cell carcinoma

Treatment of advanced renal cell carcinoma after failure of prior treatment with sunitinib or a cytokine.

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
Brain neoplasm
Breastfeeding
Galactosaemia
Gastrointestinal haemorrhage
Pregnancy
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Uncontrolled hypertension

Precautions and Warnings

Predisposition to thromboembolic disease
Tobacco smoking
Arterial aneurysm
Behcet's disease
Cerebrovascular accident
Cerebrovascular disorder
Deep vein thrombosis
Diabetes mellitus
Giant cell arteritis
Glucose-galactose malabsorption syndrome
Hepatic impairment - Child-Pugh score between 7 and 9
History of aneurysm
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Lactose intolerance
Marfan syndrome
Myocardial infarction
Occlusive peripheral arterial disease
Pulmonary embolism
Renal impairment - creatinine clearance below 15ml/minute
Retinal blood vessel occlusion
Takayasu arteritis
Thromboembolic disorder
Transient ischaemic attack
Vascular Ehlers-Danlos syndrome

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 initiated and supervised by a specialist
Contains lactose
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 haemoglobin prior to initiating therapy and periodically thereafter
Monitor hepatic function before treatment and regularly during treatment
Monitor thyroid function prior to and periodically during treatment
Monitor blood pressure regularly
Monitor for symptoms of gastrointestinal perforation or fistula
Monitor haematocrit values
Monitor patients for signs and symptoms of cardiac failure
Advise patient to report headaches, seizures, confusion, visual disturbance
Consider discontinuing therapy if significant cardiac failure develops
Consider dose reduction if cardiac failure occurs
Reduce dose if hypertension cannot be controlled
Discontinue treatment 24 hours prior to surgery
Discontinue if nephrotic syndrome occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if significant proteinuria occurs, treat and restart therapy
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
Advise patient grapefruit products may increase plasma level
May cause impaired fertility
Female: Contraception required during and for 1 week 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

Axitinib is contraindicated for use during pregnancy.

Animal studies have shown reproductive toxicity including malformations.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Axitinib is contraindicated in breastfeeding.

It is unknown whether axitinib is excreted in human milk but a risk to the nursing infant cannot be excluded.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Advise patient that if they vomit or miss a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time.

Advise patient to take orally twice daily approximately 12 hours apart with or with out food. Tablets should be swallowed whole with a glass of water.

Advise women of child bearing potential to take adequate contraception during and for 1 week after treatment.

Side Effects

Abdominal pain
Alopecia
Anaemia
Aneurysm
Artery dissection
Arthralgia
Asthenia
Cardiac failure
Cardiopulmonary failure
Cholecystitis
Congestive cardiac failure
Constipation
Cough
Decreased appetite
Decreased ejection fraction
Dehydration
Diarrhoea
Dizziness
Dry skin
Dysgeusia
Dyspepsia
Dysphonia
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Elevated TSH
Erythema
Extremity pain
Fatigue
Flatulence
Gastro-intestinal fistulae
Gastro-intestinal perforation
Glossodynia
Haemorrhage
Haemorrhoids
Headache
Hyperbilirubinaemia
Hypercalcaemia
Hyperkalaemia
Hypertension
Hypertensive crisis
Hyperthyroidism
Hypothyroidism
Increase in alkaline phosphatase
Increase in creatinine
Increase in serum ALT/AST
Leukopenia
Mucosal inflammation
Myalgia
Nausea
Neutropenia
Oropharyngeal pain
Palmar-Plantar Erythrodysaesthesia syndrome
Polycythaemia
Posterior reversible encephalopathy syndrome (PRES)
Proteinuria
Pruritus
Rash
Renal failure
Serum bilirubin increased
Stomatitis
Thrombocytopenia
Thromboembolic disorders
Tinnitus
Upper abdominal pain
Ventricular dysfunction
Vomiting
Weight loss

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 2015

Reference Sources

Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press. Accessed on 2 November 2015.

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: 10 November 2020

Summary of Product Characteristics: Inlyta 1mg 3mg, 5mg and 7mg film-coated tablets. Pfizer Ltd. November 2019.