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

Excipients: corn starch 35 mg, croscarmellose sodium (impellose) 6.5 mg, lactose monohydrate (sugar milk) 44.3 mg, povidone 3.2 mg, sodium stearyl fumarate 1 mg;

composition of film shell: Opadrai II white 4 mg, including: polyvinyl alcohol 1.6 mg, macrogol (polyethylene glycol) 0.808 mg, talc 0.592 mg, titanium dioxide 1 mg.

Dosage of 150 mg

active substance: bicalutamide 150 mg;

Excipients: corn starch 107 mg, croscarmellose sodium (impellosis) 19.5 mg, lactose monohydrate (sugar milk) 132.9 mg, povidone 7.6 mg, sodium stearyl fumarate 3 mg;

composition of film shell: Opadrai II white 12 mg, including: polyvinyl alcohol 4.8 mg, macrogol (polyethylene glycol) 2.424 mg, talc 1.776 mg, titanium dioxide 3 mg.

Description:

The tablets covered with a film membrane of white or almost white color, round, biconcave.

Pharmacotherapeutic group:Antitumor agent - antiandrogen

ATX: & nbsp

L.02.B.B.03 Bicalutamide

Pharmacodynamics:

An antitumor agent, a nonsteroidal antiandrogenic drug is a competitive antagonist of endogenous androgens. By binding to receptors on the surface of the cells of target organs, they make them inaccessible to androgens, thereby increasing the concentration of hormones in the plasma. The result of this is the regression of prostate tumors.

The use of bicalutamide in a dose of 150 mg / day in patients with localized (T₁-T₂, N0 or NX, M0) or locally advanced (T₃-T₄, any N, M0; any T, N+, M0) prostate cancer reduces the risk of progression of the disease and the relative risk of metastasis in the bone.

At the same time, the effectiveness of bicalutamide in relation to survival rates is lower than that for surgical castration.

In some patients, discontinuation may lead to the development of the syndrome of "withdrawal" of antiandrogens (after the abolition of 10-15% of patients, the temporary stabilization of the disease occurs).

Pharmacokinetics:

After intake, quickly and completely absorbed from the gastrointestinal tract (GIT) (eating does not affect absorption). The connection with plasma proteins is 96-99%. Intensively metabolized in the liver (by oxidation and the formation of conjugates with glucuronic acid) to inactive (S) - and active (R) -enantiomers. Time to reach the maximum concentration in the blood plasma (TC_mOh) (R) -enantiomer was 31.3 hours.

(R) -enantiomer is eliminated much faster from the body (R) -enantiomer, half-life (T_1/2) the last - about 7 days. With a daily intake of bicalutamide at a dose of 150 mg / day, the equilibrium concentration in the blood plasma (Css) (R) -enantiomer, 22 μg / ml. When Css About 99% of all enantiomers circulating in the blood are active (R) -enantiomer. With daily intake of concentration (R) -enantiomer in plasma increases approximately 10-fold due to prolonged T_1/2. It is excreted as metabolites by the kidneys and with bile in equal proportions. Pharmacokinetics (R) -enantiomer does not depend on age, the state of kidney function against a background of moderate impairment of liver function; In patients with severe impairment of liver function, elimination is slowed (R) -enantiomer from the plasma.

Indications:

- Monotherapy or adjuvant therapy, in combination with an analogue of gonadotropin-releasing hormone (GnRH) or surgical castration, a common prostate cancer;

- treatment of locally advanced prostate cancer (T₃-T₄, any N, M0, T₁-T₂, N+, M0) as monotherapy or adjuvant therapy in combination with radical prostatectomy or radiotherapy;

- treatment of locally advanced nonmetastatic prostate cancer in cases where surgical castration or other drugs are not effective or unacceptable.

Contraindications:

- Hypersensitivity to bicalutamide or other components of the drug;

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

- women;

- childhood;

- simultaneous reception with terfenadine, astemizole and cisapride.

Carefully:

When the liver function is impaired.

Pregnancy and lactation:

Bicalutamide Canon is contraindicated in women and should not be given to pregnant women or during lactation.

Dosing and Administration:

Adult men, including the elderly:

When common prostate cancer in combination with an analogue of GnRH or surgical castration: inside by 50 mg once a day.

With locally advanced prostate cancer: inside by 150 mg once a day.

Bicalutamide should be taken continuously for at least 2 years.

If signs of disease progression appear, the drug should be discontinued.

Impaired renal function:

Correction of the dose is not required.

Impaired liver function:

With a mild violation of liver function, dose adjustment is not required. In patients with violations of the liver function of medium and severe degree, cumulation of the drug may be observed - dose correction is required.

Side effects:

Classification of WHO frequency of development of side effects:

very often - ≥1/10 appointments (> 10%)

often from ≥1/100 up to < 1/10 appointments (>1 % and <10%)

infrequently - from ≥1/1000 up to <1/100 appointments (>0,1% and <1%)

rarely from ≥1/10000 up to <1/1000 appointments (>0,01% and <0,1%)

very rarely - <1/10000 appointments (<0,01%)

Classification of undesirable adverse reactions in accordance with the damage to organs and organ systems (medical dictionary for regulatory activities Med-DRA)

Immune system disorders:

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

Disorders from the endocrine system:

very often - gynecomastia (can persist even after cessation of therapy, especially in case of taking the drug for a long time), tenderness of the mammary glands; often - reduced sexual desire, erectile dysfunction, decreased or increased body weight, hyperglycemia, diabetes mellitus.

Impaired nervous system:

often - asthenic syndrome, dizziness, insomnia or drowsiness, anxiety, decreased appetite; rarely - depression, "hot flashes" of blood to the face.

Heart Disease:

often - angina, development or aggravation of heart failure, increased blood pressure.

Disturbances from the respiratory system, organs of the thorax and mediastinum:

rarely - 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, gastric bleeding, dryness of the oral mucosa.

Disorders from the liver and bile ducts:

rarely - transient increase in the activity of "liver" transaminases, cholestasis, 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.

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 region.

Laboratory and instrumental data:

often: anemia.

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 in the urine unchanged.

Interaction:

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

In studies in vitro shown, that (R) -enantiomer of bicalutamide inhibits CYP 3A4, to a lesser extent affecting the activity of isoenzymes CYP 2С9, 2С19, 2D6. In clinical studies using phenazone as a marker of cytochrome P450 activity (CYP), the potential ability of the drug to interact with other drugs was not revealed, however, when bicalutamide was used for 28 days against the background of midazolam, the area under the concentration-time curve (AUC) of 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, blockers of "slow" calcium channels; drugs that inhibit microsomal liver enzymes, for example, with cimetidine or ketoconazole (a dose reduction of these drugs may be required). Simultaneous application can lead to an increase in bicalutamide concentration in the plasma and, possibly, an increase in the incidence of side effects.

It enhances the effect of anticoagulants of the coumarin series, including warfarin (competition for protein binding). 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. Given the possibility of slowing down excretion of bicalutamide and accumulation of bicalutamide in patients with severe hepatic impairment, it is advisable to periodically assess 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 and severe hepatic impairment.

Heavy violations of the liver with the use of the drug are rare, reported cases with fatal outcome. In the case of pronounced changes in liver function and / or functional tests, more than 2 once taken, the drug should be discontinued.

When co-administered with cyclosporin, after the start of use or withdrawal bicalutamide recommended careful monitoring of cyclosporin plasma concentrations and condition of the patient.

In patients with progression of the disease against a background of increasing concentrations of prostate-specific antigen (ASA), 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.

Form release / dosage:

Film-coated tablets, 50 mg and 150 mg.

Packaging:

For tablets with a dosage of 50 mg: 7, 10 or 30 tablets per contour cell packaging made of polyvinyl chloride film and aluminum foil printed lacquered. By 2, 4 contour cell packs of 7 tablets or 1, 3, 6 contour cell packs of 10 tablets, or 1, 2 circuit cell packs of 30 tablets together with the instructions for use are placed in a pack of cardboard.

For tablets with a dosage of 150 mg: 7, 10 or 15 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil printed lacquered. By 2, 4 contour cell packs of 7 tablets or 1, 3, 6 contour cell packs of 10 tablets, or 2, 4 circuit cells per 15 tablets together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001745

Date of registration:02.07.2012

Expiration Date:02.07.2017

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Representation: & nbspCANONFARMA PRODUCTION CJSC CANONFARMA PRODUCTION CJSC Russia

Information update date: & nbsp21.11.2015

Illustrated instructions

Instructions

Bicalutamide Canon (Bicalutamide Canon)