Anastrozole: the steroid you need

Release Form

Tablets, film-coated.

Composition

1 tablet contains:

Active ingredients: 1 mg anastrozole.

Excipients: lactose monohydrate (200 mesh), lactose monohydrate (spray dried), Povidone K30, sodium carboxymethylstarch (type A), magnesium stearate.

The composition of the film-coating: Opadry White 02G28619 (hypromellose (E464), titanium dioxide (E171), macrogol 6000, macrogol 400).

Packaging

28 or 56 pieces.

pharmachologic effect

pharmacodynamics

Anticancer agent, an inhibitor of estrogen synthesis.

Anastrozole is highly selective nonsteroidal aromatase inhibitor – an enzyme, whereby in postmenopausal women androstenedione in peripheral tissues is converted into estrone and then to estradiol. Reducing the concentration of circulating estradiol in women with breast cancer has a therapeutic effect. In postmenopausal women, anastrozole at a daily dose of 1 mg estradiol concentration causes a decrease of 80%.

Anastrozole has no progestogenic, androgenic and estrogenic activity. The daily doses of 10 mg to no effect on the secretion of aldosterone and cortisol, therefore the application is not required substitution anastrozole corticosteroids. Details

Pharmacokinetics

Absorption and distribution

 

After oral anastrozole is rapidly absorbed from the gastrointestinal tract. Cmax plasma is usually achieved within 2 hours after ingestion (fasting). Food slightly decreases the rate of absorption, but not its extent and does not result in a clinically significant effect on the Css in plasma drug in single dose daily dose of anastrozole.

 

After 7-day dosing is achieved approximately 90-95% Css anastrozole plasma. Recorded anastrozole pharmacokinetic parameters depending on the time or dose not. Binding to plasma proteins – 40%.

 

Metabolism and excretion

 

Anastrozole is extensively metabolised in postmenopausal women, with less than 10% excreted by the kidneys in unchanged form within 72 hours after ingestion. T1 / 2 of anastrozole plasma is 40-50 hours. Metabolism anastrozole carried N-dealkylation, hydroxylation and glucuronidation. The metabolites of anastrozole are derived primarily by the kidneys. Anastrozole major metabolite – triazol determined in blood plasma does not possess pharmacological activity.

 

Pharmacokinetics in special clinical situations

 

The pharmacokinetics of anastrozole is independent of age in postmenopausal women.

 

Clearance of anastrozole after oral intake in liver cirrhosis or renal dysfunction does not change.

 

testimony

Adjuvant treatment of early breast cancer with positive hormone receptors in postmenopausal women;

first-line treatment of locally advanced breast cancer with positive or unknown hormone receptor in postmenopausal women;

a second line therapy for advanced breast cancer progressing after treatment with tamoxifen.

Contraindications

  • Premenopauznom period;
  • severe hepatic impairment (safety and efficacy have not been established);
  • concomitant therapy with tamoxifen or drugs containing estrogen;
  • pregnancy;
  • lactation (breastfeeding);
  • Children’s age (safety and efficacy in children has not been established);
  • hypersensitivity to anastrozole or other components of the preparation.

Precautions: should be prescribed for osteoporosis, hypercholesterolemia, coronary heart disease, liver dysfunction, severe renal insufficiency (creatinine clearance <20 mL / min), lactase deficiency, lactose intolerance, malabsorption of glucose / galactose (in the dosage form of the drug contains lactose). Read more

 

Dosing and Administration

The drug is taken orally. The tablet is swallowed whole with water. It is recommended to take the drug at the same time, regardless of the meal.

 

Adults, including the elderly, appoint 1 mg orally 1 time / day for a long time. If signs of progression of the disease taking the drug should be discontinued. As an adjuvant therapy recommended duration of treatment – 5 years.

 

If the kidney function dose adjustment is required.

 

Dose adjustment in patients with mild to moderate impaired liver function is not required.

 

Pregnancy and breast-feeding

Contraindicated use of the drug during pregnancy and lactation.

 

Side effects

The frequency of adverse reactions listed below was determined according to the following criteria:

 

  • very often (? 1/10);
  • common (> 1/100, <1/10);
  • sometimes (> 1/1000, <1/100);
  • rare (> 1/10 000, <1/1000);
  • very rare (<1/10 000), including isolated reports.

Since the cardiovascular system: very often – flushing.

 

From the musculoskeletal system: very often – arthralgia; rarely – trigger finger.

 

On the part of the reproductive system: often – dryness of the vaginal mucosa, vaginal bleeding (mainly in the first weeks after the cancellation or replacement of prior hormonal therapy anastrozole).

 

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

 

From the digestive system: very often – nausea; often – diarrhea, vomiting, anorexia.

 

On the part of the hepatobiliary system: increased ALT, AST and alkaline phosphatase; rarely – increased activity of GGT and bilirubin, hepatitis.

 

From the nervous system: very often – headache; often – increased drowsiness, carpal tunnel syndrome (mainly observed in patients with risk factors for the disease).

 

On the part of metabolism: often – hypercholesterolemia. The drug can cause a reduction in bone mineral density due to reduced circulating estradiol concentrations, thereby increasing the risk of osteoporosis and bone fractures.

 

Allergic reactions: often – allergic reactions; very rare – anaphylactoid reactions, angioedema, urticaria, anaphylactic shock.

 

Other: very often – asthenia.

 

Drug interactions

Studies on the interaction with the drug cimetidine and antipyrine indicate that clinically significant drug interactions mediated by cytochrome P450 isozymes in the combined use with other drugs anastrozole unlikely. Clinically significant drug interactions when using anastrozole in conjunction with other commonly prescribed drugs available. At the moment, there are no data on the use of anastrozole in combination with other anticancer drugs. Formulations containing estrogen, anastrozole reduced pharmacological action, and therefore, they should not be administered concurrently with anastrozole. There should be appointed along with tamoxifen anastrozole, because it can weaken the pharmacological action of the latter. Details