Drugs List

Therapeutic Indications

Uses

Advanced and/or metastatic renal cell cancer
Unresectable or metastatic malignant gastrointestinal stromal tumour (GIST)
Unresectable or metastatic pancreatic neuroendocrine tumours

Treatment of unresectable and/or metastatic malignant gastrointestinal stromal tumour (GIST) after failure of imatinib mesilate treatment due to resistance or intolerance.

Treatment of advanced and/or metastatic renal cell carcinoma (MRCC).

Treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumours with disease progression (pNET).

Contraindications

Children under 18 years
Breastfeeding
Congestive cardiac failure
Long QT syndrome
Lung cancer
Pregnancy
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Torsade de pointes
Uncontrolled severe hypertension

Precautions and Warnings

Family history of long QT syndrome
Tobacco smoking
Behcet's disease
Bradycardia
Cardiac disorder
Cerebrovascular disorder
Dehydration
Diabetes mellitus
Electrolyte imbalance
Giant cell arteritis
History of aneurysm
History of cardiac disorder
History of thromboembolic disorder
History of torsade de pointes
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Marfan syndrome
Occlusive peripheral arterial disease
Renal impairment
Takayasu arteritis
Vascular Ehlers-Danlos syndrome

Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals, anti-emetics & antacids may be required during therapy
Consider a dental exam & appropriate preventive dentistry before treatment
Consider premedication with hypouricaemic agent
Ensure hypertension is controlled prior to treatment
Maintain adequate hydration of patient prior / during treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Measurement of LV ejection fraction recommended before and during treatment
Monitor hepatic function before treatment and regularly during treatment
Monitor thyroid function prior to & every 3 months during therapy
Perform full blood count before each treatment cycle
Screen patient for hypertension and control as appropriate
Consider monitoring ECG in patients at risk of QT prolongation
Diabetic control may need adjustment
If rash develops, consider possibility of Stevens-Johnson Syndrome
Monitor blood glucose closely in patients with diabetes mellitus
Monitor blood pressure regularly
Monitor for bleeding during treatment
Monitor for protein in urine
Monitor for signs of CHF in patients with a history of cardiac events
Monitor patients for signs of tumour lysis syndrome
Monitor patients receiving concurrent anticoagulants
Monitor serum electrolytes
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of thrombotic microangiopathy
Suspend treatment if symptomatic hypoglycaemia occurs
Symptoms of hypothyroidism should be investigated
Discontinue before elective surgery: impairs wound healing
Discontinue if fistulae develop during treatment
Discontinue if Grade 4 proteinuria occurs (Nephrotic syndrome)
Discontinue if necrotising fasciitis occurs
Discontinue if pancreatitis occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if severe skin reaction occurs
Discontinue if symptoms of hepatic disease occur
Discontinue if thrombotic microangiopathy is confirmed
Interrupt treatment and/or reduce dose if LVEF <50% & >20% below baseline
Interrupt treatment if angioedema due to hypersensitivity occurs
Suspend treatment in severe hypertension that cannot be controlled
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
May cause impaired fertility
Female: Ensure adequate contraception during treatment
Advise patient on giving up smoking
Advise patient urine may be discoloured
Advise patients that depigmentation of hair and skin may occur

Haemorrhage and tumour bleeding
Haemorrhagic events, some of which were fatal, reported in clinical studies with sunitinib and during post-marketing surveillance have included gastrointestinal, respiratory, urinary tract, and brain haemorrhages. Tumour haemorrhage may occur suddenly, and in the case of pulmonary tumours, may present as severe and life-threatening haemoptysis or pulmonary haemorrhage. Cases of pulmonary haemorrhage, some with fatal outcome, have been observed in clinical studies and have been reported in post marketing experience in patients treated with sunitinib for MRCC, GIST, and lung cancer.

Haematological disorders
Decreased absolute neutrophil counts and platelet counts were reported in association with sunitinib. Anaemia has been observed to occur early as well as late with treatment with sunitinib.

Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
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.

Thrombotic Microangiopathy (TMA)
TMA including thrombotic thrombocytopaenia purpura (TTP) and haemolytic uraemic syndrome (HUS), sometimes leading to renal failure or fatal outcomes has been reported in patients treated with sunitinib. TMA should be considered in patients presenting with haemolytic anaemia, thrombocytopenia, fatigue, fluctuating neurologic manifestation, renal impairment and fever. If TMA develops sunitinib should be discontinued and prompt treatment initiated.

Thyroid dysfunction
Baseline laboratory measurement of thyroid function is recommended in all patients. Patients with pre-existing thyroid dysfunction should be treated as per standard medical practice prior to the start of sunitinib treatment. In addition, patients should be observed closely for signs and symptoms of thyroid dysfunction during treatment, and patients who develop any signs/symptoms should have laboratory testing of thyroid function as clinically indicated.

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.

Osteonecrosis of the jaw (ONJ)
Treatment with sunitinib may be a risk for the development of ONJ. Patients treated with sunitinib who have previously received bisphosphonates, or treated concurrently with bisphosphonates, may be particularly at risk. Invasive dental procedures should be avoided in patients who have previously received or who are currently receiving, intravenous bisphosphonates.

Pregnancy and Lactation

Pregnancy

Sunitinib is contraindicated during pregnancy.

The manufacturer does not recommend using sunitinib during pregnancy unless the potential benefit outweighs the potential risk to the foetus. If the patient becomes pregnant they should be made aware of the potential hazard. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Sunitinib is contraindicated during breastfeeding.

Use of sunitinib when breastfeeding is contraindicated by the manufacturer. Animal data reports significant levels of sunitinib in the breast milk, however presence in human breast milk is unknown. Effects on exposed infants are unknown.

Side Effects

Abdominal distension
Acne
Acute adrenal insufficiency
Alopecia
Anaemia
Aneurysm
Angioedema
Anorexia
Artery dissection
Arthralgia
Asthenia
Blistering
Cardiac failure
Cerebrovascular accident
Cheilitis
Chills
Chromaturia
Colitis
Congestive cardiac failure
Cough
Creatine phosphokinase increased
Decreased ejection fraction
Dehydration
Depression
Dizziness
Dry mouth
Dry skin
Dysgeusia
Dysphagia
Dyspnoea
Eczema
Elevated amylase levels
Elevated serum lipase
Elevated TSH
Epistaxis
Erythema
Erythema multiforme
Exfoliative dermatitis
Fatigue
Fistulae
Flushing
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal symptoms
Glossodynia
Haemorrhoids
Headache
Hepatic failure
Hepatitis
Hyperaesthesia
Hyperkeratosis
Hypertension
Hypoaesthesia
Hypothyroidism
Increase in serum ALT/AST
Increased lacrimation
Infections
Insomnia
Intravascular coagulation (disseminated)
Leucopenia
Lymphopaenia
Mouth ulcers
Mucosal inflammation
Muscle spasm
Myalgia
Myopathy
Nasal congestion
Nephrotic syndrome
Neutropenia
Oedema
Osteonecrosis (primarily of the jaw)
Pain
Palmar-plantar erythrodysaesthesia
Pancreatitis
Paraesthesia
Periorbital oedema
Peripheral neuropathy
Peritoneal haemorrhage
Pleural effusion
Pneumothorax
Prolongation of QT interval
Proteinuria
Pruritus
Pulmonary embolism
Pulmonary haemorrhage
Pyoderma gangrenosum
Pyrexia
Rash
Respiratory failure
Reversible posterior leucoencephalopathy syndrome (RPLS)
Rhabdomyolysis
Skin discolouration
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Thrombotic microangiopathy
Toxic epidermal necrolysis
Tumour haemorrhage
Weight loss
Wound healing retarded

Presentation

Capsules containing sunitinib.

Drugs List

Therapeutic Indications

Uses

Advanced and/or metastatic renal cell cancer
Unresectable or metastatic malignant gastrointestinal stromal tumour (GIST)
Unresectable or metastatic pancreatic neuroendocrine tumours

Treatment of unresectable and/or metastatic malignant gastrointestinal stromal tumour (GIST) after failure of imatinib mesilate treatment due to resistance or intolerance.

Treatment of advanced and/or metastatic renal cell carcinoma (MRCC).

Treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumours with disease progression (pNET).

Dosage

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

Adults

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Congestive cardiac failure
Long QT syndrome
Lung cancer
Pregnancy
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Torsade de pointes
Uncontrolled severe hypertension

Precautions and Warnings

Family history of long QT syndrome
Tobacco smoking
Behcet's disease
Bradycardia
Cardiac disorder
Cerebrovascular disorder
Dehydration
Diabetes mellitus
Electrolyte imbalance
Giant cell arteritis
History of aneurysm
History of cardiac disorder
History of thromboembolic disorder
History of torsade de pointes
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Marfan syndrome
Occlusive peripheral arterial disease
Renal impairment
Takayasu arteritis
Vascular Ehlers-Danlos syndrome

Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals, anti-emetics & antacids may be required during therapy
Consider a dental exam & appropriate preventive dentistry before treatment
Consider premedication with hypouricaemic agent
Ensure hypertension is controlled prior to treatment
Maintain adequate hydration of patient prior / during treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Measurement of LV ejection fraction recommended before and during treatment
Monitor hepatic function before treatment and regularly during treatment
Monitor thyroid function prior to & every 3 months during therapy
Perform full blood count before each treatment cycle
Screen patient for hypertension and control as appropriate
Consider monitoring ECG in patients at risk of QT prolongation
Diabetic control may need adjustment
If rash develops, consider possibility of Stevens-Johnson Syndrome
Monitor blood glucose closely in patients with diabetes mellitus
Monitor blood pressure regularly
Monitor for bleeding during treatment
Monitor for protein in urine
Monitor for signs of CHF in patients with a history of cardiac events
Monitor patients for signs of tumour lysis syndrome
Monitor patients receiving concurrent anticoagulants
Monitor serum electrolytes
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of thrombotic microangiopathy
Suspend treatment if symptomatic hypoglycaemia occurs
Symptoms of hypothyroidism should be investigated
Discontinue before elective surgery: impairs wound healing
Discontinue if fistulae develop during treatment
Discontinue if Grade 4 proteinuria occurs (Nephrotic syndrome)
Discontinue if necrotising fasciitis occurs
Discontinue if pancreatitis occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if severe skin reaction occurs
Discontinue if symptoms of hepatic disease occur
Discontinue if thrombotic microangiopathy is confirmed
Interrupt treatment and/or reduce dose if LVEF <50% & >20% below baseline
Interrupt treatment if angioedema due to hypersensitivity occurs
Suspend treatment in severe hypertension that cannot be controlled
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
May cause impaired fertility
Female: Ensure adequate contraception during treatment
Advise patient on giving up smoking
Advise patient urine may be discoloured
Advise patients that depigmentation of hair and skin may occur

Haemorrhage and tumour bleeding
Haemorrhagic events, some of which were fatal, reported in clinical studies with sunitinib and during post-marketing surveillance have included gastrointestinal, respiratory, urinary tract, and brain haemorrhages. Tumour haemorrhage may occur suddenly, and in the case of pulmonary tumours, may present as severe and life-threatening haemoptysis or pulmonary haemorrhage. Cases of pulmonary haemorrhage, some with fatal outcome, have been observed in clinical studies and have been reported in post marketing experience in patients treated with sunitinib for MRCC, GIST, and lung cancer.

Haematological disorders
Decreased absolute neutrophil counts and platelet counts were reported in association with sunitinib. Anaemia has been observed to occur early as well as late with treatment with sunitinib.

Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
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.

Thrombotic Microangiopathy (TMA)
TMA including thrombotic thrombocytopaenia purpura (TTP) and haemolytic uraemic syndrome (HUS), sometimes leading to renal failure or fatal outcomes has been reported in patients treated with sunitinib. TMA should be considered in patients presenting with haemolytic anaemia, thrombocytopenia, fatigue, fluctuating neurologic manifestation, renal impairment and fever. If TMA develops sunitinib should be discontinued and prompt treatment initiated.

Thyroid dysfunction
Baseline laboratory measurement of thyroid function is recommended in all patients. Patients with pre-existing thyroid dysfunction should be treated as per standard medical practice prior to the start of sunitinib treatment. In addition, patients should be observed closely for signs and symptoms of thyroid dysfunction during treatment, and patients who develop any signs/symptoms should have laboratory testing of thyroid function as clinically indicated.

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.

Osteonecrosis of the jaw (ONJ)
Treatment with sunitinib may be a risk for the development of ONJ. Patients treated with sunitinib who have previously received bisphosphonates, or treated concurrently with bisphosphonates, may be particularly at risk. Invasive dental procedures should be avoided in patients who have previously received or who are currently receiving, intravenous bisphosphonates.

Pregnancy and Lactation

Pregnancy

Sunitinib is contraindicated during pregnancy.

The manufacturer does not recommend using sunitinib during pregnancy unless the potential benefit outweighs the potential risk to the foetus. If the patient becomes pregnant they should be made aware of the potential hazard. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Sunitinib is contraindicated during breastfeeding.

Use of sunitinib when breastfeeding is contraindicated by the manufacturer. Animal data reports significant levels of sunitinib in the breast milk, however presence in human breast milk is unknown. Effects on exposed infants are unknown.

Side Effects

Abdominal distension
Acne
Acute adrenal insufficiency
Alopecia
Anaemia
Aneurysm
Angioedema
Anorexia
Artery dissection
Arthralgia
Asthenia
Blistering
Cardiac failure
Cerebrovascular accident
Cheilitis
Chills
Chromaturia
Colitis
Congestive cardiac failure
Cough
Creatine phosphokinase increased
Decreased ejection fraction
Dehydration
Depression
Dizziness
Dry mouth
Dry skin
Dysgeusia
Dysphagia
Dyspnoea
Eczema
Elevated amylase levels
Elevated serum lipase
Elevated TSH
Epistaxis
Erythema
Erythema multiforme
Exfoliative dermatitis
Fatigue
Fistulae
Flushing
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal symptoms
Glossodynia
Haemorrhoids
Headache
Hepatic failure
Hepatitis
Hyperaesthesia
Hyperkeratosis
Hypertension
Hypoaesthesia
Hypothyroidism
Increase in serum ALT/AST
Increased lacrimation
Infections
Insomnia
Intravascular coagulation (disseminated)
Leucopenia
Lymphopaenia
Mouth ulcers
Mucosal inflammation
Muscle spasm
Myalgia
Myopathy
Nasal congestion
Nephrotic syndrome
Neutropenia
Oedema
Osteonecrosis (primarily of the jaw)
Pain
Palmar-plantar erythrodysaesthesia
Pancreatitis
Paraesthesia
Periorbital oedema
Peripheral neuropathy
Peritoneal haemorrhage
Pleural effusion
Pneumothorax
Prolongation of QT interval
Proteinuria
Pruritus
Pulmonary embolism
Pulmonary haemorrhage
Pyoderma gangrenosum
Pyrexia
Rash
Respiratory failure
Reversible posterior leucoencephalopathy syndrome (RPLS)
Rhabdomyolysis
Skin discolouration
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Thrombotic microangiopathy
Toxic epidermal necrolysis
Tumour haemorrhage
Weight loss
Wound healing retarded

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: June 2019

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: 10 November 2020

Summary of Product Characteristics: Sunitinib Accord 37.5mg hard capsules. Accord Healthcare Limited. Revised May 2021.

Summary of Product Characteristics: Sutent capsules. Pfizer Limited. Revised October 2019.