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Anastrozol Kabi

Препарат Анастрозол Каби. Fresenius Kabi Gmbh (Фрезениус Каби) Германия

Producer: Fresenius Kabi Gmbh (Frezenius Kabi) Germany

Code of automatic telephone exchange: L02BG03

Release form: Firm dosage forms. Tablets.

Indications to use: Breast cancer.

General characteristics. Structure:

Active ingredient: 1 mg of an anastrozol.

Excipients: lactoses monohydrate, sodium carboxymethylstarch, K30 povidone, magnesium stearate.

Structure of a cover: опадрай white (Y-1-7000) (gipromelloza of 5 cP, titanium dioxide, macrogoal 400).

Pharmacological properties:

Pharmacodynamics. Antineoplastic drug, inhibitor of synthesis of estrogen. Anastrozol is the high-selection nonsteroid inhibitor of aromatase - enzyme by means of which at women in a postmenopause androstendion in peripheral fabrics turns into estrone and further into oestradiol. Decrease in concentration of the circulating oestradiol at patients with cancer of a mammary gland renders therapeutic effect. In a postmenopause анастрозол in a daily dose of 1 mg causes decrease in concentration of oestradiol by 80% in women.

Anastrozol has no progestagenny, androgenic and oestrogenic activity. In daily doses to 10 mg does not render effect on secretion of cortisol and Aldosteronum, therefore, at use of an anastrozol replaceable introduction of corticosteroids is not required.

Pharmacokinetics. Absorption and distribution. After intake анастрозол it is quickly soaked up from a GIT. Cmax in a blood plasma is usually reached during 2 h after intake (on an empty stomach). Food slightly reduces the absorption speed, but not its degree and does not lead to clinically significant influence on equilibrium concentration of drug in a blood plasma at a single dose of a daily dose of an anastrozol. There are no data on dependence of pharmacokinetic parameters of an anastrozol from time or a dose.

After 7-day administration of drug about 90-95% of equilibrium concentration of an anastrozol in a blood plasma are reached. Communication with proteins of a blood plasma - 40%.

Metabolism and removal. Anastrozol is extensively metabolized at women in a postmenopause, at the same time less than 10% are excreted by kidneys in not changed look during 72 h after administration of drug. T1/2 of an anastrozol makes 40-50 h of a blood plasma. Metabolism of an anastrozol is carried out by N - dealkylation, a hydroxylation and a glyukuronidation. Metabolites of an anastrozol are removed preferential by kidneys. The main metabolite of an anastrozol - the triazole defined in a blood plasma has no pharmacological activity.

Pharmacokinetics in special clinical cases. The pharmacokinetics of an anastrozol does not depend on age of women in a postmenopause.

The clearance of an anastrozol after oral administration at cirrhosis or a renal failure does not change.

Indications to use:

— adjuvant therapy of an early breast cancer, with positive hormonal receptors at women in a postmenopause, including after 2-3 summer adjuvant therapies by Tamoxifenum;

— the first line of therapy of a locally-spread or metastatic breast cancer, with positive or unknown hormonal receptors at women in a postmenopause;

— the second line of therapy of the widespread breast cancer progressing after treatment by Tamoxifenum.

Route of administration and doses:

Appoint 1 mg of 1 times/days. The tablet should be swallowed entirely, washing down with water.

It is recommended to accept drug at the same time regardless of meal.

Duration of treatment depends on a form and disease severity (at adjuvant therapy the recommended treatment duration - 5 years). At emergence of signs of progressing of a disease administration of drug should be stopped.

Features of use:

Use at pregnancy and feeding by a breast. Drug use Anastrozol Kabi is contraindicated at pregnancy and during breastfeeding.

Use at abnormal liver functions. Use at the expressed liver failure is contraindicated (safety and efficiency is not established).

With care it is necessary to use drug at an abnormal liver function.

The clearance of an anastrozol after oral administration at cirrhosis does not change.

Use at renal failures. The clearance of an anastrozol after oral administration at a renal failure does not change.

With care it is necessary to use drug at a heavy renal failure (KK <20 ml/min.).

Use for children. Contraindication: children's age. Safety and efficiency at children is not established.

Special instructions. In case of doubts in the hormonal status of the patient the menopause has to be confirmed with definition of concentration of sex hormones in blood serum.

In case of the remaining uterine bleeding against the background of reception of an anastrozol consultation and observation of the gynecologist is necessary.

There are no data on use of an anastrozol for patients with heavy degree of abnormal liver functions.

At patients with osteoporosis or with the increased risk of development of osteoporosis, the mineral density of a bone tissue should be estimated by a densitometry method, for example, DEXA scanning (a two-power x-ray absorbtsiometriya) in an initiation of treatment and it is regular on its extent. If necessary it is necessary to appoint treatment or prevention of osteoporosis and to watch carefully a condition of the patient.

As анастрозол reduces concentration of the circulating oestradiol, it can lead to decrease in mineral density of a bone tissue. Currently there are no sufficient data of rather positive influence of bisfosfonat on loss of mineral density of the bone tissue caused anastrozoly or their advantage at use for the purpose of prevention.

There are no data on simultaneous use of an anastrozol and drugs - GNRG analogs.

At women with a retseptorootritsatelny tumor to estrogen efficiency of an anastrozol was not shown, except those cases when there was a previous affirmative clinical answer on Tamoxifenum.

The drugs containing estrogen should not be appointed along with anastrozoly since these drugs will level its pharmacological action.

Efficiency and safety of an anastrozol and Tamoxifenum at their simultaneous use regardless of the status of hormonal receptors are comparable with those when using one Tamoxifenum. The exact mechanism of this phenomenon is not known yet.

It is unknown whether improves анастрозол results of treatment when sharing with chemotherapy.

Influence on ability to driving of motor transport and to control of mechanisms. Some side effects of an anastrozol, such as adynamy and drowsiness, can negatively influence ability of performance of the work demanding the increased concentration of attention and speed of psychomotor reactions. In this regard it is recommended to be careful at emergence of these symptoms at control of vehicles and mechanisms.

Side effects:

Frequency of the side reactions given below was defined according to the following criteria: very often (≥1/10), it is frequent (> 1/100, <1/10); sometimes (> 1/1000, <1/100); seldom (> 1/10000, <1/1000); very seldom (<1/10000, including separate messages).

From cardiovascular system: very often - "inflows" of blood to the person.

From a musculoskeletal system: very often — an arthralgia; seldom — a trigger finger.

From reproductive system: often - dryness of a mucous membrane of a vagina, vulval bleedings (generally within the first weeks after cancellation or change of the previous hormonal therapy on анастрозол).

From skin and skin appendages: very often - skin rash; often - thinning of hair, an alopecia; very seldom - a mnogoformny erythema (Stephens-Johnson's syndrome).

From the alimentary system: very often - nausea; often - diarrhea, vomiting, anorexia.

From gepatobiliarny system: often - increase in activity of ALT, nuclear heating plant and ShchF; seldom - increase in activity of GGT and concentration of bilirubin, hepatitis.

From a nervous system: very often - a headache; often - the increased drowsiness, a syndrome of a carpal tunnel (it was generally observed at patients with risk factors on this disease).

From metabolism: often - a hypercholesterolemia. Administration of drug can cause decrease in mineral density of a bone tissue in connection with decrease in concentration of the circulating oestradiol, thereby increasing risk of developing of osteoporosis and fractures of bones.

Allergic reactions: often - allergic reactions; very seldom - anaphylactoid reactions, a Quincke's disease, a small tortoiseshell, an acute anaphylaxis.

Others: very often - an adynamy.

Interaction with other medicines:

Researches on medicinal interaction with phenazone and Cimetidinum indicate that combined use of an anastrozol with other drugs will hardly lead to clinically significant medicinal interaction mediated by P450 cytochrome.

Clinically significant medicinal interaction at reception of an anastrozol along with other often appointed drugs is absent.

At the moment there are no data on use of an anastrozol in a combination with other antineoplastic drugs.

The drugs containing estrogen reduce pharmacological action of an anastrozol in this connection they should not be appointed along with anastrozoly.

It is not necessary to appoint Tamoxifenum along with anastrozoly as it can weaken pharmacological action of the last.

Contraindications:

— premenopauzny period;

— the expressed liver failure (safety and efficiency is not established);

— the accompanying therapy by Tamoxifenum or drugs containing estrogen;

— pregnancy;

— lactation period (feedings by a breast);

— children's age (safety and efficiency at children is not established);

— hypersensitivity to an anastrozol or other components of drug.

With care it is necessary to use drug at osteoporosis, a hypercholesterolemia, an ischemic heart disease, an abnormal liver function, a heavy renal failure (KK <20 ml/min.), insufficiency of lactase, a lactose intolerance, glyukozo-galaktozny malabsorption (the dosage form of drug contains lactose).