Tamoxifen HEXAL - instructions for use, dose, side effects, contraindications

lactose 1H₂0 71.3 mg or 142.6 mg or 213.9 mg or 285.2 mg; sodium starch glycolate 10.0 mg or 20.0 mg or 30.0 mg or 40.0 mg; Povidone 2.5 mg or 5.0 mg or 7.5 mg or 10.0 mg; cellulose microcrystalline 24.8 mg or 49.6 mg or 74.4 mg or 99.2 mg; magnesium stearate 1.2 mg or 2.4 mg or 3.6 mg or 4.8 mg. Shell

Dye white odoris 2.5 mg or 5.0 mg or 7.5 mg or 10.0 mg consisting of: lactose 0.9 mg or 1.8 mg or 2.7 mg or 3.6 mg, titanium dioxide 0 , 65 mg or 1.3 mg or 1.95 mg or 2.6 mg, hypromellose 0.7 mg or 1.4 mg or 2.1 mg or 2.8 mg, PEE 4000 0.25 mg or 0.5 mg or 0.75 mg or 1.0 mg.

Description:

Tablets 10 mg: coated tablets, round, white, or slightly yellowish, biconvex, with a uniform smooth surface. Tablets of 20 mg: coated tablets, round, white, or slightly yellowish with a notch on one side, biconvex, with a uniform smooth surface.

Tablets 30 mg: coated tablets, round, biconvex, white or slightly yellowish with a uniform smooth surface. Tablets 40 mg: coated tablets, round, biconvex, white, or slightly yellowish with a notch on one side, with a uniform smooth surface.

Pharmacotherapeutic group:An antineoplastic agent is an antiestrogen.

ATX: & nbsp

L.02.B.A.01 Tamoxifen

Pharmacodynamics:

Tamoxifen is a non-steroidal drug from the group of triphenylethylenes, which has a combined spectrum of pharmacological action, both antagonist and estrogen agonist in various tissues. In patients with breast cancer in tumor cells tamoxifen mainly manifests an anti-estrogenic effect, preventing the binding of estrogens to estrogen receptors. Tamoxifen, as well as some of its metabolites, compete with estradiol for binding sites with cytoplasmic estrogen receptors in the tissues of the mammary gland, uterus, vagina, anterior lobe of the pituitary gland, and tumors with a high estrogen receptor content. In contrast to the receptor complex of estrogen, the receptor complex of tamoxifen does not stimulate the synthesis of DNA in the nucleus, but inhibits cell division, which leads to regression of tumor cells and their death.

In women with estrogen-positive / unspecified mammary tumors, adjuvant tamoxifen therapy significantly reduces recurrence of the disease and prolongs life expectancy to 10 years. A more pronounced effect is achieved with treatment for five years than with 1 or 2-year treatment and does not depend on age, climacteric condition, dose of tamoxifen or auxiliary chemotherapy.

Approximately 10-20% of postmenopausal women tamoxifen leads to a decrease in the concentration of total cholesterol and low density lipoproteins in blood plasma. In addition, there are reports that in postmenopausal women tamoxifen preserves bone mineral density.

The variability of the clinical response to the use of tamoxifen may be associated with isozyme polymorphism CYP2D6. A low rate of metabolism may be associated with a reduced therapeutic response. There are no recommendations for tamoxifen treatment of "slow" isoenzyme metabolizers CYP2D6.

Pharmacokinetics:

After oral administration tamoxifen well absorbed. The maximum serum concentration is achieved within 4 to 7 hours after taking a single dose. The equilibrium concentration of tamoxifen in the serum with 20-40 mg / day is usually achieved after 3-4 weeks of administration. Communication with plasma proteins is 98%. Metabolized in the liver with the formation of several metabolites. The main serum metabolite, N-desmethyltamoxifen, and subsequent metabolites have almost the same anti-estrogenic properties as the original substance. Tamoxifen and its metabolites accumulate in the liver, lungs, brain, pancreas, skin and bones. Tamoxifen metabolized mainly by isoenzyme CYP3A4 before N-desmethyltamoxifen, which is further metabolized by isoenzyme CYP2D6 to another active metabolite - endoxifene. In patients with enzyme deficiency CYP2D6 the concentration of endoxyphen is approximately 75% lower than in patients with normal activity CYP2D6. The use of strong inhibitors of isoenzyme CYP2D6 in the same degree reduces the concentration of endoxifene in the blood.

Excretion of tamoxifen from the body has a two-phase character with an initial half-life of 7 to 14 hours and with a subsequent slow terminal elimination half-life within 7 days. It is allocated mainly in the form of conjugates, mainly through the intestine and only a small amount of it is excreted by the kidneys.

Indications:Adjuvant therapy for early breast cancer with estrogen-positive receptors; treatment of locally advanced or metastatic breast cancer with estrogen-positive receptors; breast cancer (including men after castration). The drug can also be used in other solid tumors resistant to standard methods of treatment, in the presence of overexpression of estrogen receptors.

Contraindications:

- Hypersensitivity to tamoxifen and / or any other component of the drug.

- Pregnancy and lactation.

- Children's age (up to 18 years).

Carefully:

Renal failure, diabetes, eye diseases (including cataracts), deep vein thrombosis and thromboembolic disease (including history), hyperlipidemia, leukopenia, thrombocytopenia, hypercalcemia, concomitant therapy with indirect anticoagulants, rare hereditary forms of intolerance lactose, a deficiency of lactase or a violation of absorption of glucose / galactose (because the tablet contains lactose).

Pregnancy and lactation:

Contraindicated use of Tamoxifen Hexal during pregnancy. There are reports of spontaneous abortions, congenital malformations and fetal death in women taking tamoxifen during pregnancy, despite the fact that the causal relationship was not established.

Breastfeeding is not possible during therapy with tamoxifen, as it inhibits lactation. With the cessation of tamoxifen, milk production does not begin for several months, due to the continued therapeutic effect of the drug. It is not known whether the tamoxifen in breast milk, so if you need treatment with Tamoxifen Hexal during breastfeeding, you should decide whether to stop breastfeeding.

Dosing and Administration:

Inside.

Tablets should be taken without chewing, squeezed a small amount of liquid, in one dose in the morning or, dividing the necessary dose into two doses, in the morning and in the evening.

The dosage regimen is usually set individually, depending on the indications. The maximum daily dose is 40 mg. As a standard dose, 20 mg of tamoxifen is recommended. When there are signs of progression of the disease, taking the drug is canceled. The duration of treatment depends on the severity of the disease, usually a long-term treatment is required. As an adjuvant therapy in women with breast cancer, the recommended duration of treatment with tamoxifen is about 5 years.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, < 1/100), rarely (> 1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

Immune system disorders: hypersensitivity.

On the part of the blood and lymphatic system often: anemia;

infrequently: leukopenia, thrombocytopenia; rarely: agranulocytosis, neutropenia; rarely: pancytopenia.

From the endocrine system

often: hypercalcemia (especially in patients with bone metastases at the beginning of therapy).

From the side of the metabolism of food

Often: fluid retention in the body;

often: an increase in the concentration of triglycerides in plasma;

rarely: significant increase in plasma concentration

triglycerides sometimes in combination with pancreatitis;

frequency is unknown: weight gain, anorexia.

From the nervous system often: headache, dizziness;

frequency is unknown: depression, confusion, photophobia,

drowsiness.

From the side of the organ of vision

often: visual impairment (sometimes reversible, including cataract, retinopathy, corneal changes);

rarely: Neuropathy of the optic nerve, optic neuritis (in rare cases with the development of blindness).

From the side of the vessels

often: leg cramps, transient ischemic attacks, thromboembolism incl.thromboembolism of pulmonary arteries (the risk of thromboembolic complications increases with combined therapy with other cytotoxic drugs), deep vein thrombosis of the lower limbs; infrequently: stroke.

From the respiratory system, organs of the chest and mediastinum

infrequently: interstitial pneumonitis.

From the gastrointestinal tract Often: nausea; often: vomiting, diarrhea, constipation.

From the liver and biliary tract

often: increased activity of "liver" transaminases, fat

hepatic dystrophy; infrequently: cirrhosis of the liver;

rarely: cholestasis, hepatitis, jaundice, necrosis of liver cells, hepatic insufficiency (including fatal outcome).

From the skin and subcutaneous tissues Often: a rash;

often: urticaria, alopecia, hypersensitivity reactions (including angioedema); rarely: vasculitis;

rarely: systemic lupus erythematosus, polymorphic erythema, Stevens-Johnson syndrome, bullous pemphigoid.

From the side of musculoskeletal and connective tissue often: myalgia;

rarely: ossalgia (pain in the bones).

From the genitals and mammary glands

Often: vaginal bleeding, vaginal discharge, menstrual cycle disorder (including amenorrhea in premenopausal women);

often: itching in the genital area, an increase in uterine fibroids,

proliferative changes in the endometrium (neoplasia, hyperplasia, polyps, rarely endometriosis); infrequently: endometrial cancer;

rarely: polycystic ovary, sarcoma of the uterus (often malignant

Müller's mixed tumor), vaginal polyposis, decreased libido in
men, impotence in men.

Congenital, family and hereditary changes rarely: late cutaneous porphyria.

General disorders and disorders at the site of administration

Often: paroxysmal sensations of heat ("hot flashes") (due to the anti-estrogen effect of tamoxifen);

rarely: pain in the affected area (especially at the beginning of therapy); frequency is unknown: increased body temperature, increased fatigue.

At the beginning of treatment, local exacerbation of the disease is possible - an increase in the size of soft-tissue formations, sometimes accompanied by severe erythema of affected areas and adjacent areas - which usually occurs within 2 weeks.

Overdose:

An acute overdose of tamoxifen in humans was not observed. It should be expected that an overdose can cause an increase in adverse reactions associated with the pharmacological action of the drug. There are also isolated reports that when tamoxifen is used in a standard dose several times a day, the interval may be extended QT.

Treatment: There is no specific antidote, treatment should be symptomatic.

Interaction:

With the simultaneous use of tamoxifen and cytostatics, the risk of thrombosis increases.

There are reports of increased tamoxifen anticoagulant effect of coumarin drugs, such as warfarin (careful monitoring is required to correct the dose of anticoagulants).

Drugs that reduce the excretion of calcium (eg, thiazide diuretics) may increase the risk of hypercalcemia.

Joint use of tamoxifen and tegafur can promote the development of active chronic hepatitis and cirrhosis of the liver.

Simultaneous use of tamoxifen with other hormones (especially estrogen-containing contraceptives) leads to a weakening of the specific action of both drugs.

With the simultaneous use of tamoxifen with drugs metabolized by isoenzyme CYP3A4 (eg, rifampicin), it is possible to reduce the plasma concentration of tamoxifen. The clinical effect is not known.

Because of the possible reduction in plasma concentrations and the clinical effect of tamoxifen when used simultaneously with potent inhibitors of isoenzyme CYP2D6 (eg, paroxetine, fluoxetine, quinidine, zincalcet, bupropion, antidepressants from the group of selective serotonin reuptake inhibitors), such combination therapy, if possible, should be avoided.

With the simultaneous use of tamoxifen and bromocriptine, an increase in plasma concentrations of tamoxifen and N-dezmethyltamoxifen.

Do not use tamoxifen simultaneously with anastrazole, since it can weaken the pharmacokinetic effect of the latter.

Special instructions:

Women who use Tamoxifen Hexal should undergo regular gynecological examination. In the treatment with tamoxifen, an increase in the incidence of endometrial cancer and uterine sarcoma (most often Müller's malignant mixed tumor) was described.The main mechanism of this pathology is unknown, but it can be associated with the estrogen-like action of tamoxifen. When bloody discharge from the vagina or vaginal bleeding occurs, the drug should be discontinued and a comprehensive examination of the patient should be carried out.

There are reports that in patients with breast cancer after treatment with tamoxifen, additional foci of the primary tumor that do not localize in the endometrium and in the opposite affected mammary gland appear. The causal relationship has not been established, the clinical significance of the observations is unknown.

In patients with bone metastases, the concentration of calcium in the serum should be determined periodically at the beginning of the treatment. In case of severe disorders, tamoxifen should be temporarily discontinued.

When signs of thrombosis of the veins of the lower limbs (pain in the legs or their swelling), pulmonary embolism (dyspnea), the use of the drug should be discontinued.

The drug Tamoxifen Hexal can cause ovulation, which increases the risk of pregnancy, in this connection, women who have an active sex life,during (and for about 3 months after) treatment with tamoxifen, the use of a mechanical or non-hormonal contraceptive is recommended.

During the period of therapy, it is necessary to periodically monitor the blood clotting parameters, the calcium content in the blood, the blood picture (leukocytes, platelets), liver function indices, blood pressure, and check with the oculist.

In case of severe thrombocytopenia, leukopenia or hypercalcemia, an individual risk assessment / expected benefit and careful medical supervision of the patient are necessary.

In patients with hyperlipidemia, the concentration of cholesterol and triglycerides in serum should be monitored during treatment.

At the beginning of tamoxifen treatment, the patient should undergo ophthalmological examination. If during the treatment with tamoxifen there are visual impairments (cataract or retinopathy), then an ophthalmological examination should be carried out as soon as possible, as some

Such violations can be eliminated after cessation of treatment, provided that the recognition is at an early stage.

Form release / dosage:

Tablets coated with 10 mg, 20 mg, 30 mg, 40 mg.

For 10 tablets in a contour mesh box made of PVC / PVDC / aluminum foil.

By 3 or 10 contour mesh packages in a cardboard box with instructions for use.

Packaging:(10) - Contour pack of PVC / PVDC / aluminum foil (10) / with instructions for use / - Cardboard tutu
(10) - Contour pack of PVC / PVDC / aluminum foil (3) / with instructions for use / - Cardboard tutu

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011849 / 01

Date of registration:17.11.2011

The owner of the registration certificate:HEXAL AG HEXAL AG Germany

Manufacturer: & nbsp

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp02.09.2015

Illustrated instructions

Instructions

Tamoxifen HEXAL (Tamoxifen HEXAL)