Anastrozol Bluefish: composition and dosage form
One film-coated tablet contains 1 mg of anastrozole. There is only one strength and it does not have to be chosen: adult patients, including the elderly, are given one tablet once a day.
The product information sets out no particulars of administration: no relation to meals, no particular time of day. The one reservation concerns the composition — the tablet contains lactose, and patients with the rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
How Anastrozol Bluefish works
Anastrozole is a potent and highly selective non-steroidal aromatase inhibitor. To see what that is for, you need to know where oestradiol comes from after the menopause. The ovaries no longer produce it, and it is formed mainly in peripheral tissues: androstenedione is converted into oestrone with the help of the aromatase enzyme complex, and oestrone then passes into oestradiol. It is precisely that chain the medicine breaks at its first link.
The figures show how thoroughly. A highly sensitive assay found that in postmenopausal women anastrozole at 1 mg a day suppresses oestradiol production by more than 80%. And the benefit of that suppression is demonstrated separately: in women with breast cancer it is exactly the fall in circulating oestradiol that produces the favourable effect. Anastrozole itself, meanwhile, has no progestogenic, androgenic or oestrogenic activity, and at doses up to 10 mg a day it does not affect the secretion of cortisol and aldosterone, measured before and after a standard corticotropic hormone challenge test. Glucocorticoid replacement during treatment is therefore not required.
Indications
There is one indication, but it holds three conditions at once and all three are compulsory: treatment of advanced breast cancer in postmenopausal women in whose tumour the presence of an oestrogen receptor has been established.
Each condition follows from the mechanism. A receptor-positive tumour is needed because the medicine works by depriving the tumour of oestrogen — in a receptor-negative tumour that lever does not act. And the postmenopausal state is fundamental because before the menopause the main source of oestrogen is the ovaries, not peripheral aromatase. The product information says so plainly: the medicine should not be used in premenopausal patients, and where the hormonal state is in doubt, luteinising hormone, follicle-stimulating hormone and oestradiol are measured to confirm the menopause.
Method of administration and dosage
The recommended dose in adult patients, including the elderly, is one tablet once a day. No selection, no titration: the dose depends neither on body weight, nor on the stage, nor on the length of treatment.
Special groups change almost nothing in that scheme. In mild to moderate renal impairment a change of dose is not recommended, and in severe impairment the medicine is used with caution. It is the same with the liver: in mild liver disease the dose is not changed, and in severe impairment caution is needed. Children and adolescents are not recommended the medicine because of insufficient data on safety and efficacy in that group. Individualising treatment here lies not in the dose but in the monitoring — and the next section is devoted to exactly that.
Contraindications
The list is short enough to fit in one sentence: the medicine is contraindicated in pregnant and breastfeeding women, and in hypersensitivity to anastrozole or to any excipient.
That brevity is deceptive. The circle of those the medicine suits is defined not by the prohibitions but by the indication itself: a postmenopausal woman with a receptor-positive tumour. Everything else is not a contraindication but a condition under which treatment calls for additional tests and monitoring.
Special warnings and precautions
The first warning has been heard already and is repeated here: before the menopause the medicine is not used, and where there is doubt the status is confirmed by measuring hormones. Two drug restrictions are added to it. There are no data on simultaneous use with LHRH analogues. And simultaneous use of tamoxifen or of medicines containing oestrogens should be avoided: they reduce the pharmacological action of anastrozole — which is logical, since the medicine is precisely what removes oestrogen.
| Situation | What the doctor does |
| Known osteoporosis or a risk of developing it | bone densitometry is carried out before treatment starts and repeated regularly during it; where there is an indication, treatment or prevention of osteoporosis is begun and its effectiveness checked regularly |
| Loss of bone mineral density during treatment | specialist medicines are considered, bisphosphonates for example, which can slow the loss of minerals caused by anastrozole in postmenopausal women |
| Moderate and severe liver impairment | the medicine has not been studied in breast cancer patients in this group, and exposure in hepatic impairment may rise; it is used with caution and the decision is made by weighing benefit and risk in each patient |
| Severe renal impairment | exposure at a filtration rate below 30 ml/min does not increase, but the medicine is still used with caution |
| Growth hormone deficiency in children | boys are not given it alongside growth hormone therapy — in the main clinical trial efficacy was not shown and safety not established; girls are likewise not allowed it as an addition to growth hormone treatment, because it lowers the oestradiol concentration |
The meaning of the first two rows of the table is worth spelling out, because it is the main long-term risk of the treatment. The medicine reduces the oestrogen content of the blood, and that can reduce bone mineral density, so that in some patients the risk of fractures rises. Separately, on driving: the medicine has no or negligible influence on the ability to drive and to operate machinery; nonetheless weakness and drowsiness have been reported during its use, and if those symptoms persist, caution is needed at the wheel.
Interaction with other medicines
This section is built in an unusual way: almost all of it is about interactions that were not found. It opens with a fact that sounds alarming — in vitro anastrozole inhibits the activity of the CYP 1A2, 2C8/9 and 3A4 isoenzymes. But clinical studies with antipyrine and warfarin showed that at a 1 mg dose it does not significantly inhibit the metabolism of either antipyrine or R- and S-warfarin. Hence the conclusion: giving it together with other medicines does not appear to cause clinically significant interactions involving the CYP isoenzymes.
The rest confirms the same picture. The enzymes involved in the metabolism of anastrozole itself have not been identified. Cimetidine, a weak non-specific inhibitor of the CYP isoenzymes, has no effect on the plasma concentration of anastrozole, and the effect of strong CYP inhibitors is not known. An analysis of safety data from clinical trials found no interactions in patients taking other commonly used medicines at the same time; nor were clinically significant interactions with bisphosphonates observed. Exactly one restriction of practical weight remains, and it has already been named: tamoxifen and oestrogens.
Pregnancy and breastfeeding
There are no data on the use of the product in pregnant women, and animal studies showed reproductive toxicity. Anastrozole is therefore contraindicated in pregnancy — one of only two contraindications it has.
With breastfeeding the position is the same in substance and in wording: there are no data on the use of anastrozole in that period, and the medicine is contraindicated in breastfeeding women. The effect on human fertility has not been studied, and animal studies showed a harmful effect on reproduction.
Adverse effects
The frequencies were calculated from the large phase three ATAC trial, in which 9,366 postmenopausal women with operable breast cancer received adjuvant treatment for 5 years — anastrozole, tamoxifen as monotherapy, or both together. A base like that gives unusually firm figures for an oncology medicine.
- very common: headache, hot flushes, rash, joint pain and stiffness, arthritis, osteoporosis, weakness;
- common: anorexia and hypercholesterolaemia; drowsiness and carpal tunnel syndrome; diarrhoea and vomiting; a rise in serum alkaline phosphatase, ALT and AST activity; thinning and loss of hair, allergic reactions; bone and muscle pain; vaginal dryness and vaginal bleeding;
- uncommon: hypercalcaemia with or without a rise in parathyroid hormone; a rise in gamma-glutamyl transferase activity and serum bilirubin, hepatitis; urticaria; trigger finger;
- rare: erythema multiforme, anaphylactoid reactions, cutaneous vasculitis including cases of Henoch-Schönlein purpura;
- very rare: Stevens-Johnson syndrome and angioedema.
Three items on that list are commented on separately in the product information. Cases of carpal tunnel syndrome were reported in the trials more often on anastrozole than on tamoxifen, but most of them occurred in patients predisposed to that condition. Vaginal bleeding was seen commonly and usually in patients with advanced breast cancer, during the first few weeks after switching from previous hormone therapy to anastrozole; if the bleeding is prolonged, a change of treatment is considered. And most important of all, the bones: at a median follow-up of 68 months the fracture rate was 22 per 1,000 patient-years in the anastrozole group against 15 in the tamoxifen group, and the incidence of osteoporosis 10.5% against 7.3%. There are no data confirming whether those figures reflect a protective effect of tamoxifen, an effect of anastrozole itself, or both at once.
Overdose
Clinical data on accidental overdose are scarce, and judging by the studies the picture is a fairly calm one. In animals the preparation showed low acute toxicity. In clinical studies healthy male volunteers were given up to 60 mg as a single dose, and postmenopausal women with advanced breast cancer up to 10 mg a day, and those doses were well tolerated. A single dose of anastrozole causing life-threatening symptoms has never been established.
There is no specific antidote for overdose and the treatment must be symptomatic. It is borne in mind that the patient may have taken several medicines at once. In a conscious person vomiting may be induced. Since the preparation is not strongly bound to proteins, dialysis may help — an unusual option for oncology tablets. After that, general supportive treatment is indicated with frequent monitoring of vital signs and close observation of the patient.
How to get a prescription for Anastrozol Bluefish online
Anastrozole has one condition without which the medicine simply does not work: the woman must be postmenopausal. Before the menopause the main source of oestrogen is the ovaries, not the peripheral aromatase the medicine acts on. That is why, with any doubt about the hormonal state, the doctor begins with a test for luteinising and follicle-stimulating hormone and oestradiol, not with a prescription. On e-zdrowie.com you fill in a medical questionnaire, the doctor reviews the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the tablets against it.
Begin the questionnaire with the hormonal state and the diagnosis: when your last period was, whether LH, FSH and oestradiol were measured, whether the presence of oestrogen receptors in the tumour was confirmed histologically, and what stage the disease is at. Report the state of your bones separately: whether osteoporosis was diagnosed, and whether and when densitometry was done — it is the one investigation that is repeated regularly during anastrozole treatment. Give any liver and kidney disease along with your latest results: in moderate and severe impairment the medicine is used with caution. And be sure to list your medicines — above all tamoxifen and any preparation containing oestrogens, topical forms included: they weaken the action of anastrozole and simultaneous use should be avoided.
