Sorafenib

Registered South African indications:

• Advanced renal cell carcinoma
• Advanced inoperable hepatocellular carcinoma
• Thyroid carcinoma

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Men and women of childbearing potential
• Severe hepatic impairment
• Elderly
• Dialysis patients
• Risk factors for aneurysms and artery dissections
  - Hypertension
  - History of aneurysm
• Diabetic patients
• QT prolongation or risk factors thereof
  - Congenital long QT syndrome
  - High cumulative dose of anthracycline therapy
  - Certain anti-arrhythmic medicines or other medicines that lead to QT prolongation
  - Electrolyte disturbances such as hypokalaemia, hypoocalcaemia, hypomagnesaemia
• Unstable coronary artery disease
• Recent myocardial infarction
• Major surgical procedures
• Patients requiring wound care therapy
• Squamous cell carcinoma of the lung treated with sorafenib in combination with platinum-based chemotherapies
• Differentiated thyroid cancer
• High-risk renal cell carcinoma patients

Forms avail. in SA and covered in this monograph: tab

Used for the treatment of

• Advanced renal cell carcinoma
  - Who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy
• Advanced inoperable hepatocellular carcinoma
• Thyroid carcinoma
  - Progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma, refractory to radioactive iodine

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Consult specialist for dosages and regimens

Not established for use in children below 18 years

Pregnancy

• Caution; positive evidence of risk in animal studies
• There are no data on the use of sorafenib in pregnant women
• Studies in animals have shown reproductive toxicity including malformations. In rats, sorafenib and its metabolites were demonstrated to cross the placenta and sorafenib is anticipated to cause harmful effects on the foetus
• Sorafenib should not be used during pregnancy unless clearly necessary, after careful consideration of the needs of the mother and risk to the foetus
• Women of childbearing potential must use effective contraception during treatment

Breastfeeding

• Caution; not recommended
• It is not known whether sorafenib is excreted in human milk. In animals, sorafenib and/or its metabolites were excreted in milk
• Because sorafenib could harm infant growth and development, women must not breastfeed during sorafenib treatment

Fertility

• Results from animal studies further indicate that sorafenib can impair male and female fertility

Renal Impairment

• No dose adjustment recommended
  No data is available in patients requiring dialysis

Hepatic Impairment

• Mild to moderate (Child-Pugh Classes A & B): No dose adjustment recommended
• Severe (Child-Pugh Class C): Caution; no information available
  Since sorafenib is mainly eliminated via the hepatic route, exposure may be increased in patients with severe hepatic impairment

Elderly            

• Caution; no dose adjustment recommended
  No dose adjustment is required in the elderly. Cases of renal failure have been reported. Monitoring of renal function in the elderly should be considered

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Peripheral sensory neuropathy
• Reversible posterior leukoencephalopathy (including life-threatening or fatal outcomes)
• Encephalopathy
• Fatigue

Cardiovascular Disorders

• Congestive cardiac failure (including life-threatening or fatal outcomes)
• Myocardial ischaemia and infarction (including life-threatening or fatal outcomes)
• QT prolongation
• Haemorrhage
  - Gastrointestinal (including life-threatening or fatal outcomes)
  - Respiratory tract (including life-threatening or fatal outcomes)
  - Cerebral (including life-threatening or fatal outcomes)
• Hypertension
• Hypertensive crisis (including life-threatening or fatal outcomes)
• Aneurysms
• Artery dissections

Respiratory Disorders

• Rhinorrhoea
• Dysphonia
• Interstitial lung disease-like events (including life-threatening or fatal outcomes)
  - Pneumonitis
  - Radiation pneumonitis
  - Acute respiratory distress

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Constipation
• Stomatitis
• Dry mouth
• Glossodynia
• Dyspepsia
• Dysphagia
• Gastro-oesophageal reflux disease
• Pancreatitis
• Gastritis
• Gastrointestinal perforations (including life-threatening or fatal outcomes)

Hepatobiliary Disorders

• Increase in bilirubin
• Jaundice
• Cholecystitis
• Cholangitis
• Drug-induced hepatitis (including life-threatening or fatal outcomes)
• Transient increase in transaminases
• Transient increase in blood alkaline phosphatase

Genitourinary Disorders

• Renal failure
• Proteinuria
• Nephrotic syndrome
• Erectile dysfunction
• Gynaecomastia

Endocrine and Metabolic Disorders

• Hypothyroidism
• Hyperthyroidism
• Anorexia
• Hypophosphataemia
• Hypocalcaemia
• Hypokalaemia
• Hyponatraemia
• Hypoglycaemia
• Dehydration
• Decreased weight
• Increased amylase
• Increased lipase

Musculoskeletal Disorders

• Arthralgia
• Myalgia
• Muscle spasms
• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Dry skin
• Rash
• Alopecia
• Hand-foot skin reaction
• Erythema
• Pruritus
• Keratoacanthoma/ squamous cell cancer of the skin
• Exfoliative dermatitis
• Acne
• Skin desquamation
• Hyperkeratosis
• Eczema
• Erythema multiforme
• Radiation recall dermatitis
• Stevens-Johnson syndrome
• Leukocytoclastic vasculitis
• Mucosal inflammation
• Toxic epidermal necrolysis (including life-threatening or fatal outcomes)
• Flushing

Immune, Blood and Lymphatic System Disorders

• Infection
• Folliculitis
• Lymphopenia
• Leucopenia
• Neutropenia
• Anaemia
• Thrombocytopenia
• Hypersensitivity reactions (including skin reactions and urticaria)
• Anaphylactic reaction
• Angioedema
• Fever
• Influenza-like illness
• Abnormal INR
• Abnormal prothrombin level

Sensory Disorders

• Tinnitus
• Dysgeusia

Other

• Pain
  - Mouth
  - Abdominal
  - Bone
  - Tumour
  - Headache

• Warfarin
• Phenprocoumon
• UGT1A1 substrates
• Irinotecan
• UGT1A9 substrates
• Docetaxel 
• Antibiotics causing major ecological disturbances of the gastrointestinal microflora
• Neomycin
• Platinum-based chemotherapies (squamous cell carcinoma of the lung)
• CYP3A4 inducers
• Rifampicin
• Phenytoin
• Carbamazepine
• Phenobarbital
• Dexamethasone
• P-glycoprotein substrates
• Digoxin
• Capecitabine 
• Doxorubicin

Other interactions

• St John's wort (Hypericum perforatum)

• Full blood count with differential
• Electrolytes
• Hepatic function
• Lipase levels
• Amylase levels
• Hepatic function
• Blood pressure

Specific  cases may require

• ECG
• Thyroid function
• International normalized ratio (INR)
• Prothrombin time
• Pregnancy test
• Renal function

Sorafenib is a multikinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is a multikinase inhibitor that decreases tumour cell proliferation in vitro. Sorafenib inhibits tumour growth of a broad spectrum of human tumour xenografts in athymic mice accompanied by a reduction of tumour angiogenesis. Sorafenib inhibits the activity of targets present in the tumour cell (CRAF, BRAF, V600E BRAF, c-KIT, and FLT-3) and in the tumour vasculature (CRAF, VEGFR-2, VEGFR-3, and PDGFR-ß). RAF kinases are serine/threonine kinases, whereas c-KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-ß are receptor tyrosine kinases.

Tablet 200mg

• Nexavar (Bayer) originator