Bicalutamide - instructions for use, dose, side effects, contraindications

auxiliary substances (core): lactose monohydrate (sugar milk) 29.50 mg, microcrystalline cellulose 10.30 mg, sodium carboxymethyl starch 4.00 mg, povidone-K17 4.00 mg, magnesium stearate 0.70 mg, water 1.50 mg;

auxiliary substances (shell): hypromellose 1.65 mg, macrogol-4000 0.45 mg, titanium dioxide 0.90 mg.

1 tablet, film-coated, 150.0 mg contains:

active substance: bicalutamide 150.0 mg;

auxiliary substances (core): lactose monohydrate (milk sugar) 88.50 mg, microcrystalline cellulose 30.90 mg, sodium carboxymethyl starch 12.00 mg, povidone-K17 12.00 mg, magnesium stearate 2.10 mg, water 4.50 mg;

auxiliary substances (shell): hypromellose 4.95 mg, macrogol-4000 1.35 mg, titanium dioxide 2.70 mg.

Description:

Round, biconvex tablets, covered with a film shell of white or almost white color.

Pharmacotherapeutic group:Antitumor agent - antiandrogen

ATX: & nbsp

L.02.B.B.03 Bicalutamide

Pharmacodynamics:

Bicalutamide is a racemic mixture with non-steroidal antiandrogenic activity predominantly (R) -enantiomer, does not have a different endocrine activity. Bicalutamide binds to androgen receptors and, without activating the expression of genes, suppresses the stimulating effect of androgens on them. The result of this is the regression of prostate tumors.

In some patients, discontinuation may lead to the development of a clinical syndrome of anti-androgen withdrawal.

When bicalutamide is used in a daily dose of 150 mg daily for the treatment of patients with locally advanced (T3-T4, any N, M0 or any T, N+, M0) with prostate cancer as monotherapy or adjuvant therapy significantly reduces the risk of disease progression and bone metastases.

With locally advanced prostate cancer, there has been a trend towards improved life expectancy without signs of disease progression in the groups of patients taking bicalutamide in a dose of 150 mg as monotherapy or adjuvant therapy in comparison with standard therapy (surgical treatment, radiotherapy).

An increase in life expectancy among patients with locally advanced prostate cancer who received bicalutamide in a dose of 150 mg as a monotherapy and as an adjuvant treatment in combination with radiation therapy.

Pharmacokinetics:

After oral administration bicalutamide quickly and completely absorbed from the gastrointestinal tract. Eating does not affect absorption.

(S) -enantiomer is eliminated much faster from the body (R) -enantiomer, half-life (T_1/2) of the last - about 7 days.

With daily intake of bicalutamide, the concentration (R) -enantiomer in the blood plasma increases approximately 10-fold due to prolonged T_1/2, which makes it possible to take the drug 1 time per day.

With a daily intake of bicalutamide in a dose of 50 mg, the equilibrium concentration (Css) (R)-enantiomer in plasma is about 9 μg / ml, 150 mg at about 22 μg / ml. At an equilibrium state, about 99% of all enantiomers circulating in the blood is active (R) -enantiomer.

Binding to plasma proteins is high (for a racemic mixture of 96%, for (R)-enantiomer, 99.6%). Intensively metabolized in the liver (by oxidation and the formation of conjugates with glucuronic acid). Metabolites are excreted by the kidneys and intestines in approximately equal proportions.

Average concentration (R) -enantiomer in the semen of men receiving the drug at a dose of 150 mg is 4.9 μg / ml.

On the pharmacokinetics (R) -enantiomer does not affect age, impaired renal function, mild or moderate liver function disorder. There is evidence that in patients with severe impairment of liver function, elimination is slowed down (R)-enantiomer from the plasma.

Indications:

Bicalutamide 50.0 mg

In combination with an analogue of GnRH (gonadotropin-releasing hormone) or surgical castration for the treatment of advanced prostate cancer.

Bicalutamide 150.0 mg

As monotherapy or adjuvant therapy in combination with radical prostatectomy or radiotherapy for patients with locally advanced prostate cancer (T3-T4, any N, M0; T1-T2, N+, M0).

As a monotherapy for the treatment of patients with locally advanced nonmetastatic prostate cancer,When surgical castration or other medical interventions are not acceptable or not applicable.

Contraindications:

- Hypersensitivity to bicalutamide or other components of the drug;

- simultaneous reception with terfenadine, astemizole and cisapride;

- children's age, female sex.

Carefully:

- Impaired liver function;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- simultaneous use of "slow" calcium channels with cyclosporine or blockers;

- simultaneous use with drugs that inhibit microsomal oxidation of drugs (cimetidine or ketoconazole).

Pregnancy and lactation:

Bicalutamide is contraindicated in women and should not be given to pregnant and lactating mothers.

Dosing and Administration:

Inside, regardless of food intake, drink a sufficient amount of liquid.

Adult and elderly men with advanced prostate cancer in combination with an analogue of GnRH or surgical castration - 50 mg once a day. Treatment with the drug must begin at the same time as the start of the GnRH analogue or surgical castration.

Adults and elderly men, with locally advanced prostate cancer - 150 mg once a day. The drug should be taken for a long time, at least for 2 years. If signs of disease progression appear, the drug should be discontinued.

There is no need for dose adjustment in patients with impaired renal function, mild violations of liver function. In patients with moderate to severe hepatic impairment, an increased cumulation of bicalutamide may be observed.

Side effects:

The frequency of adverse reactions listed below was determined according to the following criteria: very often (not less than 1/10), often (more than 1/100, less than 1/10); infrequently (more than 1/1000, less than 1/100); rarely (more than 1/10000, less than 1/1000); very rarely (less than 1/10000), including individual messages.

Immune system disorders:

Rarely - reactions of hypersensitivity, including angioedema, hives, skin rashes.

Disorders from the endocrine system:

Very often - gynecomastia (can persist even after discontinuation of therapy, especially in case of taking the drug for a long time), tenderness of the mammary glands;

Often - a decrease in sexual desire, erectile dysfunction, weight gain, hyperglycemia.

Impaired nervous system:

Often - asthenia, headache, dizziness, insomnia or drowsiness, anxiety, decreased appetite;

Rarely - depression, "tides" of blood to the face.

Heart Disease:

Often - myocardial infarction (reported cases with fatal outcome) *, development or aggravation of heart failure *, increased blood pressure.

Disturbances from the respiratory system, chest and mediastinal organs:

Rarely - shortness of breath, chest pain, cough, pharyngitis, bronchitis, pneumonia, interstitial lung diseases (including fatal outcome), rhinitis.

Disorders from the gastrointestinal tract:

Often - nausea;

Rarely - abdominal pain, indigestion, constipation, diarrhea, vomiting, flatulence.

Disorders from the liver and bile ducts:

Rarely - transient increase in the activity of "liver" transaminases, jaundice;

Very rarely - liver failure (including fatal outcome).

Disturbances from the skin and subcutaneous tissues:

Often - alopecia, hirsutism or restoration of hair growth, dry skin, itchy skin. Disturbances from the musculoskeletal and connective tissue;

Often - myasthenia gravis, myalgia, cramps, arthritis, joint contractures.

Disorders from the kidneys and urinary tract:

Infrequently - dysuria, polyuria, urinary retention, peripheral edema;

Rarely, hematuria.

General disorders and disorders at the site of administration:

Often - fever, flu-like syndrome, chills, increased sweating, pain in the pelvic area, infection.

Violations from the blood and lymphatic system:

Often: anemia.

* were observed in the treatment of prostate cancer in combination with the GnRH analogue. The risk of developing increased with simultaneous application of bicalutamide in a dose of 50 mg with the analogue of GnRH. In the case of bicalutamide 150 mg as monotherapy for the treatment of prostate cancer, an increase in the frequency of development was not evident.

Overdose:

Cases of overdose in humans are not described.

There is no specific antidote.

Treatment of overdose: symptomatic, it is necessary to monitor vital body functions. Hemodialysis is ineffective, since bicalutamide strongly binds to plasma proteins and is not excreted by the kidneys in unchanged form.

Interaction:

There is no evidence of pharmacokinetic or pharmacodynamic interactions between bicalutamide and GnRH analogues.

(R) -enantiomer of bicalutamide is an isoenzyme inhibitor CYP3A4, to a lesser extent, affect the activity of isoenzymes CYP2C9, 2C19 and 2D6. The potential for bicalutamide to interact with other drugs was not detected, however, when using the drug for 28 days against the medication of midazolam, the area under the concentration-time curve (AUC) Midazolam increases by 80%.

Inhibition of isoenzyme CYP 3A4 under the action of bicalutamide can make a difference when using drugs with a narrow therapeutic index, which are metabolized in the liver. In this regard, the simultaneous use of bicalutamide with terfenadine, astemizole, cisapride is contraindicated.

Caution should be exercised in prescribing bicalutamide simultaneously with cyclosporine or blockers of "slow" calcium channels. It may be necessary to reduce the dose of these drugs, especially in case of potentiation or the development of adverse reactions. After the beginning of the use or elimination of bicalutamide, it is recommended that the concentration of cyclosporin in the plasma be carefully monitored and the patient's clinical condition monitored.

The simultaneous use of bicalutamide and drugs depressing microsomal oxidation of drugs, for example cimetidine or ketoconazole, can lead to an increase in bicalutamide concentration in the plasma and, possibly, the incidence of side effects.

Enhances the effect of anticoagulants coumarinic series (warfarin).

Special instructions:

Bicalutamide is extensively metabolized in the liver. Considering the possibility of slowing the excretion of bicalutamide and the cumulation of bicalutamide in patients with severe impairment of liver function, it is advisable to periodically evaluate liver function. Most liver function changes occur during the first six months of treatment with the drug.

Bicalutamide should be used with caution in patients with moderate to severe hepatic impairment.

Heavy violations of the liver with the use of the drug are rare, reported cases with fatal outcome. In case of pronounced changes in liver function and / or increase in functional tests, the drug intake should be stopped more than twice.

When combined with cyclosporine,after the start of use or elimination of bicalutamide, careful monitoring of the plasma cyclosporin concentration and the patient's condition is recommended.

In patients with progression of the disease against a background of increasing concentrations of prostate-specific antigen (PSA), consideration should be given to discontinuing bicalutamide treatment.

Taking into account the possibility of drug inhibition of the activity of cytochrome P450 (isoenzyme CYP 3A4), caution should be exercised when bicalutamide is used simultaneously with preparations that are predominantly metabolized with the participation of an isoenzyme CYP 3A4. It is recommended that prothrombin time be regularly monitored when bicalutamide is administered to patients receiving indirect coumarin anticoagulants.

In patients taking GnRH agonists, a decrease in glucose tolerance was observed. This effect can lead to the development of diabetes mellitus or a decrease in glucose tolerance in patients with diabetes mellitus. In connection with this, patients receiving bicalutamide in combination with GnRH agonists, it is necessary to monitor the concentration of glucose in the blood.

Effect on the ability to drive transp. cf. and fur:

When using bicalutamide, drowsiness and dizziness may occur, so care should be taken when driving vehicles or other moving mechanisms. If these side effects occur, you should refrain from performing these activities.

Form release / dosage:

Tablets, film-coated, 50.0 mg and 150.0 mg.

Packaging:

For 10, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50, 60 or 100 tablets in cans of polyethylene terephthalate.

One jar or 1, 2, 3, 4, 5, 6 or 10 contour squares, together with the instructions for use, are placed in a cardboard package (bundle).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002358

Date of registration:03.02.2014

Expiration Date:03.02.2019

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp25.01.2017

Illustrated instructions

Instructions

Bicalutamide (Bicalutamide)