Anastrozole, 1 mg 30 pcs

Pharmacodynamics

Antitumor drug. A highly selective non-steroidal inhibitor of aromatase, the enzyme by which, in postmenopausal women, androstenedione is converted in peripheral tissues to estrone and then to estradiol. Anastrozole has no gestagenic, androgenic or estrogenic activity.

In postmenopausal women, anastrozole at a daily dose of 1 mg causes an 80% reduction in estradiol. Anastrozole in daily doses up to 10 mg has no effect on cortisol and aldosterone secretion.

Pharmacokinetics

Intake and distribution

Anastrozole is rapidly absorbed from the gastrointestinal tract after oral administration on an empty stomach. Cmax in plasma is reached within 2 hours. Food slightly reduces absorption rate (but not its degree) and does not lead to clinically significant effect on Css of the drug in plasma in a single daily dose of anastrozole. After 7 days of administration, the plasma Css of anastrozole is approximately 90-95%. Binding to plasma proteins is 40%.

Metabolism and excretion

The metabolism of anastrozole is by N -dealkylation, hydroxylation and glucuronidation. Triazole, the main metabolite determined in plasma, does not inhibit aromatase.

The T1/2 from plasma is 40-50 h. Less than 10% of the dose is excreted unchanged in the urine within 72 hours after drug administration. Metabolites are excreted mainly in the urine.

Pharmacokinetics in special clinical cases

The clearance of anastrozole after oral administration in cirrhosis or renal dysfunction is not changed.

Indications

Prevalent breast cancer in postmenopausal women.

Active ingredient

Composition

Active substances:

Anastrozole 1 mg.

Associates:

Lactose monohydrate 72 mg,

Microcrystalline cellulose 15.6 mg,

povidone 3 mg,

magnesium stearate 0.9 mg,

colloidal silicon dioxide 0.5 mg,

sodium carboxymethyl starch 2 mg.

Composition of the film coating:

Hypromellose 1.65 mg,

Macrogol-4000 0.45 mg,

Titanium dioxide 0.9 mg.

How to take, the dosage

Adults, including elderly patients, should take the drug orally at the same time 1 mg (swallow the tablet whole with water) once a day for a long time. If there are signs of disease progression the drug should be stopped.

Dose adjustment is not required in patients with mild to moderate renal impairment.

Dose adjustment is not required in patients with mild hepatic impairment.

Interaction

Studies on drug interactions with antipyrine and cimetidine indicate that clinically significant drug interactions mediated by cytochrome P450 isoenzymes are unlikely when anastrozole is coadministered with other drugs.

There are no clinically significant drug interactions when anastrozole is used concomitantly with other commonly prescribed drugs.

There is currently no information about the use of anastrozole in combination with other anticancer drugs.

The drugs containing estrogens reduce the pharmacological effects of anastrozole, so they should not be prescribed concomitantly with anastrozole.

Tamoxifen should not be prescribed at the same time as anastrozole, because it may decrease the pharmacologic effects of the latter.

Special Instructions

In women with estrogen receptor-negative tumors, the efficacy of anastrozole has not been demonstrated unless there is a previous positive clinical response to tamoxifen.

If there is any doubt about a patient’s hormonal status, menopause should be confirmed by serum sex hormone testing.

There are no data on the use of anastrozole in patients with severe hepatic impairment or in patients with significant renal impairment (QC < 20 ml/min).

In case of persistent uterine bleeding with anastrozole, a gynecologist should be consulted and monitored.

Oestrogen-containing medications should not be used concomitantly with anastrozole, because they would counteract the pharmacological effects of the latter.

Limiting circulating estradiol levels, anastrozole may decrease bone mineral density.

In patients with osteoporosis (or at risk of osteoporosis) bone mineral density should be assessed by densiometry (e.g., DEXA scan) at the start of treatment and over time. If necessary, treatment or prophylaxis for osteoporosis should be started under close medical supervision.

There are no data on concomitant use of anastrozole and LHRH analogues.

It is not known whether anastrozole improves treatment outcomes when used together with chemotherapy.

Pediatric use

The drug is contraindicated in pediatric patients.

Impact on ability to drive vehicles and other mechanisms requiring increased concentration

Some side effects of anastrozole, such as asthenia and somnolence, may adversely affect the ability to perform potentially hazardous activities requiring increased concentration and rapid psychomotor reactions. In this regard, it is recommended to be cautious while driving vehicles and mechanisms in case of appearance of these symptoms.

Contraindications

Side effects

Definition of the frequency of adverse reactions:

Reproductive system: often – vaginal dryness; rarely – vaginal bleeding (mostly during the first weeks after withdrawal or change of previous hormone therapy to anastrozole).

Digestive system disorders: frequently – nausea, diarrhea; rarely – anorexia, vomiting, increased GGT and ALP activity.

Cardiovascular system: very common – hot flashes.

CNS disorders: often – headache; rarely – somnolence.

Co musculoskeletal system: often – arthralgia.

Dermatological reactions: frequently – thinning of hair, skin rash; very rarely – erythema multiforme (Stevens-Johnson syndrome).

Mechanical disorders: rare – hypercholesterolemia; possibly – decreased bone mineral density in connection with a decrease in circulating estradiol levels (risk of osteoporosis and bone fractures).

Others: frequent – asthenia; very rare – allergic reactions (including angioedema, urticaria, anaphylactic shock).

Overdose

Symptoms: A single dose of anastrozole that could lead to life-threatening symptoms has not been determined.

Treatment: In case of overdose, treatment should be symptomatic.

If the patient is conscious, it is appropriate to induce vomiting.

General supportive therapy, monitoring of the patient and monitoring the function of vital organs and systems is recommended. Dialysis may be performed. There is no specific antidote.