Exemestane

Registered South African indications:

• Oestrogen receptor positive metastatic breast cancer
• Early or late oestrogen receptor positive breast cancer in postmenopausal women

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients 
• Pregnancy 
• Breastfeeding 
• Pre-menopausal woman

Cautions 

• Renal impairment
• Hepatic impairment 
• Decreased bone mineral density 
• Vitamin D deficiency 
• Osteoporosis
• Hereditary fructose intolerance
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency

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

Oestrogen receptor positive metastatic breast cancer

• Oral (tab): 25mg, dly; Treatment duration: Until disease progression

Early or late oestrogen receptor positive breast cancer in postmenopausal women

• Oral (tab): 25mg, dly; Treatment duration: See additional prescribing points

Not established for use in children

Pregnancy 

• Contraindicated
• No clinical data on exposed pregnancies are available with exemestane
• Studies on animals have shown reproductive toxicity, exemestane is,  therefore, contraindicated in pregnant women
• The physician needs to discuss the necessity of adequate contraception with women who have the potential to become pregnant including women who are perimenopausal or who have recently become postmenopausal, until their postmenopausal status is fully established

Breastfeeding 

• Contraindicated 
• It unknown whether exemestane is excreted in human milk, therefore, exemestane should not be administered to lactating women

Renal Impairment 

• eGFR ≥30- 69 mL/min: No dose adjustment recommended 
• eGFR ≤29 mL/min: Not recommended

Hepatic Impairment 

• Mild to moderate (Child-Pugh Classes A and B): no dose adjustment recommended
• Severe (Child-Pugh Class C): Not recommended

Elderly 

• No dose adjustment recommended

Porphyria Information

• Probably porphyrinogenic (PRP)

Central Nervous System Disorders

• Insomnia
• Depression
• Headache
• Dizziness
• Carpal tunnel syndrome
• Paraesthesia
• Somnolence
• Asthenia

Cardiovascular Disorders

• Hot flushes

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
• Constipation
• Dyspepsia
• Diarrhoea

Hepatobiliary Disorders

• Hepatitis
• Cholestatic hepatitis
• Increased hepatic enzymes
• Increased serum bilirubin
• Increased serum alkaline phosphatase

Endocrine and Metabolic Disorders

• Anorexia 

Musculoskeletal Disorders

• Joint and musculoskeletal pain
• Osteoporosis
• Fracture 

Immune, Blood and Lymphatic System Disorders

• Leucopenia
• Thrombocytopenia
• Hypersensitivity

Skin and Subcutaneous Tissue Disorders

• Increased sweating 
• Rash
• Alopecia
• Urticaria
• Pruritus 
• Acute generalised exanthematous pustulosis

• CYP3A4 inducers
• Oestrogen-containing medication  
• Rifampicin
• Phenytoin
• Carbamazepine
• St. John's Wort

• Bone density
• Vitamin D levels

Specific cases may require 

• Luteinizing hormone
• Follicle-stimulating hormone 
• Oestradiol levels

Treatment duration in early or late breast cancer

• 5 years of hormonal blockade is recommended, this can be achieved with 5 years of continuous Exemestane treatment 

OR

• 2-3 years of Exemestane treatment followed by 2-3 years of Tamoxifen treatment

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• Exemestane should not be administered to women with pre-menopausal endocrine status. The post-menopausal status should be ascertained by assessment of LH, FSH and oestradiol levels
• Exemestane tablets may contain methyl parahydroxybenzoate which may cause 'delayed' allergic reactions (possibly delayed)
• Routine assessment of 25-hydroxy vitamin D levels prior to the start of aromatase inhibitor treatment should be considered, due to the high prevalence of severe deficiency in women with early breast cancer. Women with Vitamin D deficiency should receive supplementation with Vitamin D

Exemestane is an irreversible, steroidal aromatase inhibitor, structurally related to the  natural substrate androstenedione. In post-menopausal women, oestrogens are produced primarily from the conversion of androgens into oestrogens through the aromatase enzyme in peripheral tissues. Oestrogen deprivation through aromatase inhibition, significantly lowers circulating estrogen in postmenopausal woman where breast cancer growth is estrogen dependent and thus an effective and selective treatment for hormone dependent breast cancer.

Tablet 25mg

• Actamasin 25 (Accord Healthcare)
• Aspen exemestane (Pharmacare)
• Aromasin (Pfizer) originator
• Equisin (Equity)
• Exican (Ranbaxy)