Drugs List

Therapeutic Indications

Uses

Advanced renal cell carcinoma- interferon alpha/interleukin2 therapy failed
Differentiated thyroid cancer (DTC)
Hepatocellular carcinoma

Advanced renal cell carcinoma in patients who have failed to respond to prior treatment with interferon-alpha or interleukin-2 based therapy, or are considered unsuitable for such therapy.

Hepatocellular carcinoma.

Progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hurthle cell) thyroid carcinoma that is refractory to radioactive iodine.

Contraindications

Children under 18 years
Breastfeeding
Long QT syndrome
Pregnancy
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
History of anthracycline therapy
Recent major surgery
Risk of haemorrhage
Tobacco smoking
Behcet's disease
Cerebrovascular disorder
Diabetes mellitus
Electrolyte imbalance
Giant cell arteritis
History of aneurysm
History of torsade de pointes
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Marfan syndrome
Occlusive peripheral arterial disease
Recent myocardial infarction
Renal dialysis
Severe hepatic impairment
Takayasu arteritis
Uncontrolled hypertension
Unstable cardiac disorder
Vascular Ehlers-Danlos syndrome

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Correct electrolyte disorders before treatment
Ensure hypertension is controlled prior to treatment
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Monitor thyroid stimulating hormone (TSH) before & during treatment
Monitor blood pressure regularly
Monitor ECG in patients at risk of QT prolongation
Monitor patients receiving concurrent anticoagulants
Monitor prothrombin times closely in patients on anticoagulant therapy
Monitor renal function in elderly patients
Monitor serum calcium levels
Monitor serum electrolytes
Potential for increased risk of bleeding
Suspend treatment if symptomatic hypoglycaemia occurs
Discontinue if blood pressure cannot be controlled
Discontinue if cardiac ischaemia and / or infarction develops
Discontinue if haemorrhage occurs
Discontinue if severe skin reaction occurs
Discontinue treatment if gastrointestinal perforation occurs
Interrupt treatment in patients undergoing major surgery
May cause impaired fertility
Female: Ensure adequate contraception during treatment
Advise patient on giving up smoking

As sorafenib is mainly eliminated via the hepatic route, exposure may be increased in patients with severe hepatic impairment (Child Pugh C).

Monitoring of fluid balance and electrolytes is advised in patients at risk of renal dysfunction. Safety in patients patients requiring dialysis is unknown.

Dermatological toxicities should be managed with topical therapy for symptomatic relief in addition to treatment interruption and/or dose modification. Consider permament discontinuation in severe or persistent cases.

Patients with differentiated thyroid cancer (DTC) with tumours that infiltrate the trachea, bronchus or oesophagus should be treated with localized therapy before administering sorafenib due to the potential risk of bleeding.

Hypocalcaemia is more commonly reported in patients treated for DTC, especially those with a history of hypoparathyroidism. Close monitoring of serum calcium levels is recommended.

The effects of sorafenib on wound healing are unknown. As such, the decision to resume therapy following major surgical procedures should be based on clinical judgement of adequate wound healing.

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

Sorafenib is contraindicated in pregnancy.

At the time of writing there is no adequate data available on the use of sorafenib in human pregnancy.

Animal studies indicate sorafenib and it's metabolites cross the placenta and have shown reproductive toxicity, including malformations. As sorafenib inhibits angiogenesis, a critical component of embryonic and foetal development, use during pregnancy is anticipated to cause foetal harm.

The manufacturer states that sorafenib should not be used during pregnancy unless clearly necessary, after careful consideration of the needs of the mother and risk to the foetus.

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

Sorafenic is contraindicated in breast feeding.

It is not known whether sorafenib is excreted in human breast milk. Excretion has been observed in animal studies and based on the molecular weight and long elimination half life of sorafenib, excretion in human breast milk is likely to occur. Exposure to sorafenib could harm infant growth and development and as such, the manufacturer states that women must not breast feed during sorafenib treatment.

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

Abnormal INR
Acne
Acute respiratory distress
Alopecia
Altered prothrombin concentration
Anaemia
Anaphylactic reaction
Angioedema
Anorexia
Arthralgia
Asthenia
Cholangitis
Cholecystitis
Congestive cardiac failure
Constipation
Dehydration
Depression
Desquamation
Diarrhoea
Dry mouth
Dry skin
Dysgeusia
Dyspepsia
Dysphagia
Dysphonia
Eczema
Elevated serum lipase
Encephalopathy
Erectile dysfunction
Erythema
Erythema multiforme
Exfoliative dermatitis
Fatigue
Fever
Flushing
Folliculitis
Gastritis
Gastro-intestinal perforation
Gastroesophageal reflux disease
Glossodynia
Gynaecomastia
Haemorrhage
Hand-foot syndrome
Headache
Hepatitis
Hyperkeratosis
Hypersensitivity reactions
Hypertension
Hypertensive crisis
Hyperthyroidism
Hypocalcaemia
Hypoglycaemia
Hypokalaemia
Hyponatraemia
Hypophosphataemia
Hypothyroidism
Increase in serum alkaline phosphatase (reversible)
Increased amylase secretion
Increases in serum transaminases (transient)
Infections
Influenza-like symptoms
Interstitial lung disease
Jaundice
Leucopenia
Leukocytoclastic vasculitis
Lymphopaenia
Mucosal inflammation
Muscle spasm
Myalgia
Myocardial infarction
Myocardial ischaemia
Nausea
Nephrotic syndrome
Neutropenia
Pain
Pancreatitis
Peripheral neuropathy
Pneumonitis
Prolongation of QT interval
Proteinuria
Pruritus
Radiation recall dermatitis
Rash
Renal failure
Reversible posterior leucoencephalopathy syndrome (RPLS)
Rhabdomyolysis
Rhinorrhoea
Serum bilirubin increased
Skin reactions
Squamous cell carcinoma
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Urticaria
Vomiting
Weight loss

Presentation

Oral formulations of sorafenib.

Drugs List

Therapeutic Indications

Uses

Advanced renal cell carcinoma- interferon alpha/interleukin2 therapy failed
Differentiated thyroid cancer (DTC)
Hepatocellular carcinoma

Advanced renal cell carcinoma in patients who have failed to respond to prior treatment with interferon-alpha or interleukin-2 based therapy, or are considered unsuitable for such therapy.

Hepatocellular carcinoma.

Progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hurthle cell) thyroid carcinoma that is refractory to radioactive iodine.

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
Long QT syndrome
Pregnancy
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
History of anthracycline therapy
Recent major surgery
Risk of haemorrhage
Tobacco smoking
Behcet's disease
Cerebrovascular disorder
Diabetes mellitus
Electrolyte imbalance
Giant cell arteritis
History of aneurysm
History of torsade de pointes
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Marfan syndrome
Occlusive peripheral arterial disease
Recent myocardial infarction
Renal dialysis
Severe hepatic impairment
Takayasu arteritis
Uncontrolled hypertension
Unstable cardiac disorder
Vascular Ehlers-Danlos syndrome

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Correct electrolyte disorders before treatment
Ensure hypertension is controlled prior to treatment
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Monitor thyroid stimulating hormone (TSH) before & during treatment
Monitor blood pressure regularly
Monitor ECG in patients at risk of QT prolongation
Monitor patients receiving concurrent anticoagulants
Monitor prothrombin times closely in patients on anticoagulant therapy
Monitor renal function in elderly patients
Monitor serum calcium levels
Monitor serum electrolytes
Potential for increased risk of bleeding
Suspend treatment if symptomatic hypoglycaemia occurs
Discontinue if blood pressure cannot be controlled
Discontinue if cardiac ischaemia and / or infarction develops
Discontinue if haemorrhage occurs
Discontinue if severe skin reaction occurs
Discontinue treatment if gastrointestinal perforation occurs
Interrupt treatment in patients undergoing major surgery
May cause impaired fertility
Female: Ensure adequate contraception during treatment
Advise patient on giving up smoking

As sorafenib is mainly eliminated via the hepatic route, exposure may be increased in patients with severe hepatic impairment (Child Pugh C).

Monitoring of fluid balance and electrolytes is advised in patients at risk of renal dysfunction. Safety in patients patients requiring dialysis is unknown.

Dermatological toxicities should be managed with topical therapy for symptomatic relief in addition to treatment interruption and/or dose modification. Consider permament discontinuation in severe or persistent cases.

Patients with differentiated thyroid cancer (DTC) with tumours that infiltrate the trachea, bronchus or oesophagus should be treated with localized therapy before administering sorafenib due to the potential risk of bleeding.

Hypocalcaemia is more commonly reported in patients treated for DTC, especially those with a history of hypoparathyroidism. Close monitoring of serum calcium levels is recommended.

The effects of sorafenib on wound healing are unknown. As such, the decision to resume therapy following major surgical procedures should be based on clinical judgement of adequate wound healing.

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

Sorafenib is contraindicated in pregnancy.

At the time of writing there is no adequate data available on the use of sorafenib in human pregnancy.

Animal studies indicate sorafenib and it's metabolites cross the placenta and have shown reproductive toxicity, including malformations. As sorafenib inhibits angiogenesis, a critical component of embryonic and foetal development, use during pregnancy is anticipated to cause foetal harm.

The manufacturer states that sorafenib should not be used during pregnancy unless clearly necessary, after careful consideration of the needs of the mother and risk to the foetus.

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

Sorafenic is contraindicated in breast feeding.

It is not known whether sorafenib is excreted in human breast milk. Excretion has been observed in animal studies and based on the molecular weight and long elimination half life of sorafenib, excretion in human breast milk is likely to occur. Exposure to sorafenib could harm infant growth and development and as such, the manufacturer states that women must not breast feed during sorafenib treatment.

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 women of child bearing potential that they must use effective contraception during treatment.

Advise patients that Sorafenib should be administered without food or with a low or moderate fat meal. If the patient intends to have a high fat meal the tablets should be taken at least 1 hour before or 2 hours after the meal.

Side Effects

Abnormal INR
Acne
Acute respiratory distress
Alopecia
Altered prothrombin concentration
Anaemia
Anaphylactic reaction
Angioedema
Anorexia
Arthralgia
Asthenia
Cholangitis
Cholecystitis
Congestive cardiac failure
Constipation
Dehydration
Depression
Desquamation
Diarrhoea
Dry mouth
Dry skin
Dysgeusia
Dyspepsia
Dysphagia
Dysphonia
Eczema
Elevated serum lipase
Encephalopathy
Erectile dysfunction
Erythema
Erythema multiforme
Exfoliative dermatitis
Fatigue
Fever
Flushing
Folliculitis
Gastritis
Gastro-intestinal perforation
Gastroesophageal reflux disease
Glossodynia
Gynaecomastia
Haemorrhage
Hand-foot syndrome
Headache
Hepatitis
Hyperkeratosis
Hypersensitivity reactions
Hypertension
Hypertensive crisis
Hyperthyroidism
Hypocalcaemia
Hypoglycaemia
Hypokalaemia
Hyponatraemia
Hypophosphataemia
Hypothyroidism
Increase in serum alkaline phosphatase (reversible)
Increased amylase secretion
Increases in serum transaminases (transient)
Infections
Influenza-like symptoms
Interstitial lung disease
Jaundice
Leucopenia
Leukocytoclastic vasculitis
Lymphopaenia
Mucosal inflammation
Muscle spasm
Myalgia
Myocardial infarction
Myocardial ischaemia
Nausea
Nephrotic syndrome
Neutropenia
Pain
Pancreatitis
Peripheral neuropathy
Pneumonitis
Prolongation of QT interval
Proteinuria
Pruritus
Radiation recall dermatitis
Rash
Renal failure
Reversible posterior leucoencephalopathy syndrome (RPLS)
Rhabdomyolysis
Rhinorrhoea
Serum bilirubin increased
Skin reactions
Squamous cell carcinoma
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Urticaria
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: October 2018

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Nexavar 200mg film-coated tablets. Bayer. Revised June 2018.

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

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen
Sorafenib Last revised: 19 August 2016
Last accessed: 04 October 2018