Bikalutamide Grindeks - instructions for use, dose, side effects, contraindications

Bicalutamide is a competitive antagonist of endogenous androgens. By binding to receptors on the surface of cells of target organs, bicalutamide makes them inaccessible to endogenous androgens, while increasing the concentration of hormones in the plasma. The result is regression of malignant neoplasms of the prostate gland. In some patients, discontinuing bicalutamide may lead to the development of a clinical syndrome of "withdrawal" of antiandrogens.

Pharmacokinetics:

After oral administration bicalutamide quickly and completely absorbed from gastrointestinal tract (eating does not affect absorption).

Bicalutamide is extensively metabolized in the liver by oxidation and the formation of conjugates with glucuronic acid: inactive (S) - and active (R) -enantiomers, the bond of the latter with plasma proteins is 96-99%.

TS_m_Oh (R) -enantiomer, 31.3 parts (S) -enantiomer is eliminated much faster from the body (R) -enantiomer, T_1/2the last - about 7 days. Due to the long half-life, the concentration (R) -enantiomer in plasma increases approximately 10-fold. With a daily intake of bicalutamide in a dose of 50 mg, the equilibrium concentration (R) -enantiomer in plasma is 9 μg / ml. When taking the drug at a dose of 150 mg / day, the equilibrium concentration in the plasma is 22 μg / ml. Displayed bicalutamide in the form of metabolites by the kidneys and with bile in equal proportions.

Pharmacokinetics (R) -enantiomer does not depend on age, kidney function, mild or moderate liver function disorder; In patients with severe impairment of liver function, elimination is slowed (R) -enantiomer from the plasma.

Indications:

- Common prostate cancer in combination with an analogue of GnRH (gonadotropin-releasing hormone) or surgical castration.

- Locally spread prostate cancer (T3-T4, any N, M0, T1-T2, N +, M0) as monotherapy or adjuvant therapy in combination with radical prostatectomy or radiotherapy.

- Locally non-metastatic prostate cancer in cases where surgical castration or other medical interventions are not applicable or are unacceptable.

Contraindications:

- Hypersensitivity to bicalutamide and auxiliary components of the drug;

- simultaneous reception with terfenadine, astemizole and cisapride;

- bicalutamide should not be assigned to children and women.

Carefully:- Liver failure;

lactose intolerance;

- deficiency of lactase, glucose-galactose malabsorption.

Pregnancy and lactation:

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

Dosing and Administration:

With advanced prostate cancer In combination with an analogue of GnRH or surgical castration, BIKALOUTAMIDE GRINDEX is taken internally at 50 mg / day.

With locally advanced prostate cancer as a monotherapy or adjuvant therapy - 150 mg / day.

BIKALUTAMIDE GRINDEX should be taken continuously for at least 2 years. If signs of disease progression appear, the drug should be discontinued.

If there is a violation of kidney function, dose adjustment is not required.

Patients with moderate and severe impairment of liver function require a dose adjustment due to possible cumulation of the drug. With mild violations of the liver, dose adjustment is not required.

Side effects:

The pharmacological action of bicalutamide can cause the following side effects:

Often (> 10%): gynecomastia (may persist even after cessation of therapy, especially if the drug is taken for a long time), tenderness of the mammary glands, hot flushes;

often (≥1% and <10%): diarrhea, nausea, transient increase in activity "hepatic" transaminases, cholestasis and jaundice (described changes in liver function were rarely evaluated as serious, transient, completely disappeared or decreased with continued therapy or after drug withdrawal), itching, asthenia; when using the drug in a daily dose of 150 mg - alopecia or hair regrowth, decreased sexual desire, sexual dysfunction, weight gain;

rarely (≥0.1% - <1%): hypersensitivity reactions, including angioedema and urticaria, interstitial lung diseases; when using the drug in a daily dose of 150 mg - abdominal pain, depression, dyspepsia, hematuria;

rarely (> 0.01% - <0.1%): vomiting, dry skin (with the use of the drug in a daily dose of 150 mg, skin dryness is often observed), liver failure (cause-and-effect relationship with bicalutamide is not established).

With the simultaneous use of bicalutamide and GnRH analogs, the following adverse events with a frequency of ≥ 1% can also be observed:

- from the cardiovascular system: heart failure;

- from the gastrointestinal tract: anorexia, dry mouth, indigestion, constipation, flatulence;

- from the central nervous system: dizziness, headache, insomnia, increased drowsiness;

- from the respiratory system: shortness of breath;

- from the genitourinary system: sexual dysfunction, nocturia;

- from the hematopoietic system: anemia;

- from the skin and subcutaneous tissues: alopecia, skin rash, excessive sweating, hirsutism;

- Other: diabetes, hyperglycemia, increased or decreased body weight, abdominal pain, chest pain, pelvic pain, chills.

Overdose:

Cases of overdose in humans are not described. There is no specific antidote.

Treatment symptomatic. Dialysis is ineffective, because bicalutamide strongly binds to proteins and is not excreted in the urine unchanged. It shows general supportive therapy and monitoring of vital body functions.

Interaction:

Evidence of pharmacokinetic or pharmacodynamic interaction between the preparation BIKALUTAMIDE GRINDEX and analogues of GnRH is not obtained.

In studies in vitro It was shown that the (R) -enantiomer of bicalutamide is an inhibitor of the CYP 3A4 isoenzyme, to a lesser extent affecting the activity of the CYP 2C9, 2C19, and 2D6 isoenzymes. In clinical studies using phenazone as a marker for the activity of cytochrome detected P450 (CYP) potential to bicalutamide for interaction with other drugs, however, the application of bicalutamide for 28 days in patients receiving midazolam area under "concentration-time" curve (AUC) Midazolam increased by 80%.

Contraindicated with the simultaneous use of bicalutamide with drugs such as terfenadine, astemizole and cisapride.

Care should be taken when using bicalutamide simultaneously with cyclosporine or blockers of "slow" calcium channels. It may be necessary to reduce the dose of these drugs, especially if side effects develop. After the beginning of the application or removal of bicalutamide, careful monitoring of the concentration of cyclosporin in the plasma and the clinical state of the patient is recommended.

Be cautious with the simultaneous use of bicalutamide and drugs that inhibit microsomal liver enzymes, for example, with cimetidine or ketoconazole. Simultaneous application may lead to an increase in bicalutamide concentration in the plasma and possibly an increase in the incidence of side effects.

Strengthens the effect of indirect anticoagulants coumarinovogo number, including warfarin (competition for communication with proteins). It is recommended that prothrombin time be regularly monitored when bicalutamide is administered to patients receiving indirect coumarin anticoagulants.

Special instructions:

Bicalutamide is extensively metabolized in the liver. Taking into account the possibility of slowing down the excretion, bicalutamide and cumulation of bicalutamide in patients with pronounced impairment of liver function, it is advisable to periodically evaluate liver function.

Most changes in liver function occur during the first six months of treatment with bicalutamide. Bicalutamide should be used with caution in patients with moderate to severe liver dysfunction. Heavy hepatic changes with bicalutamide rarely occur, reports of fatal cases have been reported. In case of pronounced changes in liver function, bicalutamide should be discontinued.

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.

Given the potential for inhibition of cytochrome P450 (isoenzyme CYP3A4) activity by bicalutamide, caution should be exercised with simultaneous the use of bicalutamide with drugs predominantly metabolized with the participation of the 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:

Bicalutamide does not affect the ability of patients to drive vehicles or engage in other potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 50 mg.

Packaging:

For 10 tablets in a planar cell package made of a polyvinylchloride film and aluminum foil or in a contoured cell pack made of a polyvinyl chloride film with a polyvinylidene chloride coating and aluminum foil.

3 contour packs of 10 tablets together with instructions for use are placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-001398

Date of registration:28.12.2011

Expiration Date:28.12.2016

Date of cancellation:2018-04-09

The owner of the registration certificate:GRINDEX, JSC GRINDEX, JSC Latvia

Manufacturer: & nbsp

Grindeks, JSC Latvia

Representation: & nbspGrindeks Rus, Open CompanyGrindeks Rus, Open CompanyRussia

Information update date: & nbsp09.04.2018

Illustrated instructions

Instructions

Bicalutamide Grindeks (Bicalutamid Grindex)