Aromasin 25mg Tablet

Aromasin is indicated for the following:

• Treatment of advanced oestrogen receptor positive breast cancer in women with natural or induced postmenopausal status whose disease has progressed following anti-oestrogen therapy.
• Adjuvant treatment of postmenopausal women with oestrogen receptor positive invasive early breast cancer who are disease free, following at least 2 years of initial adjuvant tamoxifen therapy.

Adults and elderly patients: The recommended dose of AROMASIN is one 25 mg tablet to be taken once daily, preferably after a meal.

In patients with:

• Advanced breast cancer, treatment with AROMASIN should continue until tumour progression is evident.
• Early breast cancer, treatment with Aromasin should continue until completion of five years of adjuvant hormonal therapy (anti-oestrogen followed by Aromasin), or until tumour relapse occurs.

No dose adjustments are required for patients with hepatic or renal insufficiency.

Children: Not recommended for use in children.

AROMASIN tablets are contra-indicated in patients with a known hypersensitivity to exemestane or to any of the excipients, in pre-menopausal women and in pregnant or lactating women.

Effects on ability to drive and use machines: Drowsiness, somnolence, asthenia and dizziness have been reported with the use of the medicine. Patients should be advised that, if these events occur, their physical and/or mental abilities required for operating machinery or driving a car may be impaired.

Due to its mode of action, Aromasin should not be administered to pre-menopausal women. Therefore, the postmenopausal status should be ascertained by assessment of LH, FSH and oestradiol levels.

Aromasin should not be co-administered with oestrogen-containing medicines as these would negate its pharmacological action.

During adjuvant treatment with Aromasin, women with osteoporosis or at risk of osteoporosis should have their bone mineral density formally assessed by bone densitometry at the commencement of treatment and at regular intervals thereafter. Treatment or prophylaxis for osteoporosis should be initiated as appropriate and carefully monitored.

In vitro evidence showed that the exemestane is metabolised through cytochrome P450 (CYP) 3A4 and aldoketoreductases and does not inhibit any of the major CYP isoenzymes. In a clinical pharmacokinetic study, the specific inhibition of CYP 3A4 by ketoconazole showed no significant effects on the pharmacokinetics of Aromasin. In a pharmacokinetic interaction study with rifampicin, a potent CYP 3A4 inducer, the pharmacologic activity (i.e. oestrogen suppression) was not affected, despite an about 50% decrease in the C max and AUC of exemestane.

AROMASIN is contra-indicated in pregnant or lactating women. If AROMASIN is taken accidentally, administration should be immediately discontinued.

Drowsiness, somnolence, asthenia and dizziness have been reported with the use of the medicine. Patients should be advised that, if these events occur, their physical and/or mental abilities required for operating machinery or driving a car may be impaired.

In the clinical studies conducted with Aromasin, the discontinuation rate due to adverse events was 2,8 % in the overall patient population with advanced breast cancer receiving the standard dose of 25 mg and 6,3% in patients with early breast cancer receiving adjuvant treatment with Aromasin following initial adjuvant tamoxifen therapy.

In patients with early breast cancer, the most commonly reported adverse reactions were hot flushes (21%) and fatigue (16%). Most adverse reactions can be attributed to the normal pharmacological consequences of oestrogen deprivation (e.g. hot flushes).

The side-effects were categorized utilizing the incidence rate as follows:

Very Common: >1/10 (>10%)
Common: >1/100 and u22641/10 (>1% and u226410%)
Uncommon: >1/1000 and u22641/100 (>0,1% and u22641%)
Rare: >1/10 000 and u22641/1000 (>0,01% and u22640,1%)

System Organ Class Frequency Adverse Events
Metabolism and nutrition disorders Common Anorexia
Psychiatric disorders Very Common Insomnia
Common Depression
Nervous system disorders Very Common Headache
Common Dizziness, carpal tunnel syndrome
Uncommon Somnolence
Vascular disorders Very common Hot flushes
Gastrointestinal disorders Very Common Nausea
Common Abdominal pain, vomiting, constipation, dyspepsia, diarrhoea
Skin and subcutaneous tissue disorders Very Common Increased sweating
Common Rash, alopecia
Musculoskeletal and bone disorders Common Joint and musculoskeletal pain
General disorders and administration site conditions Very Common Fatigue
Common Pain, peripheral oedema
Uncommon Asthenia
Blood and lymphatic system disorders In patients with Advanced Breast Cancer, thrombocytopenia and leucopenia have been rarely reported. An occasional decrease in lymphocytes has been observed in approximately 20 % of patients receiving Aromasin, particularly in patients with pre-existing lymphopenia; however, mean lymphocyte values in these patients did not change significantly over time. This effect has not been observed in patients treated for early breast cancer.
Hepatobiliary disorders Elevations of liver enzymes have been observed. Elevation of alkaline phosphatase and bilirubin was very commonly observed, although usually not associated with elevation of liver enzymes.

Clinical trials have been conducted with Aromasin given up to 800 mg in a single dose to healthy female volunteers and up to 600 mg daily to postmenopausal women with advanced breast cancer; these dosages were well tolerated. The single dose of Aromasin that could result in life-threatening symptoms is not known. In rats and dogs, lethality was observed after single oral doses equivalent to 2000 and 4000 times, respectively, the recommended human dose on a mg/mu00b2 basis. There is no specific antidote to overdosage and treatment must be symptomatic. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.