Bilumid - instructions for use, doses, side effects, contraindications

composition of the shell: hydroxypropylmethylcellulose, povidone, polysorbate, talc, titanium dioxide, yellow water-soluble dye or quinoline yellow.

Description:

The tablets covered with a cover of yellow color, round, biconcave form (for a dosage of 50 mg).

The tablets covered with a cover of yellow color, round, biconcave form. On the cross-section, two layers are visible (for a dosage of 150 mg).

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. The result is regression of malignant neoplasms of the prostate gland.

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

Pharmacokinetics:

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

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

With a daily intake of 150 mg of bicalutamide, the equilibrium concentration (R) -enantiomer in plasma increases approximately 10-fold due to a long half-life, which makes it possible to take the drug once a day.

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

Pharmacokinetics (R) -enantiomer does not depend on age, renal dysfunction, mild or moderate liver function disorder. There is evidence that in patients with severe impairment of liver function, elimination is slowed (R) -enantiomer from the plasma.

The association with 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 in urine and bile approximately in equal proportions.

Indications:

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

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

- mDisseminated nonmetastatic prostate cancer in cases where surgical castration or other medical interventions are inapplicable or unacceptable.

Contraindications:

- Hypersensitivity to bicalutamide or any other auxiliary components included in the formulation;

- simultaneous reception with terfenadine, astemizole and cisapride;

- Bilumide® should not be administered to women or children.

Carefully:Violation of the function of the liver.

Dosing and Administration:

Adults and older men:

With advanced prostate cancer in combination with an analogue of GnRH or surgical castration: inside of 50 mg (1 tablet of 50 mg) once a day.

Treatment with Bilumide® it is necessary to start at the same time as the beginning of the GnRH analogue or surgical castration.

With locally advanced prostate cancer: inside by 150 mg (1 a tablet of 150 mg or 3 tablets of 50 mg) once a day. Bilumide® should be taken for a long time, at least for 2 years. If signs of disease progression appear, the drug should be discontinued.

Renal impairment: dose adjustment is not required.

Dysfunction of the liver: with a mild violation of liver function correction of the dose is not required. In patients with moderate to severe hepatic impairment, an increased cumulation of Bilumida®.

Side effects:

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

- very often (> 10%): gynecomastia (can persist even after cessation of therapy, especially in case of taking the drug for a long time), tenderness of the mammary glands, hot flushes;

- often (> 1% and <10%): diarrhea, nausea, transient increase in the activity of "liver" transaminases, cholestasis and jaundice (described changes in liver function were rarely evaluated as serious, transient, completely disappeared or decreased with continued therapy or after 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 hives, interstitial lung diseases; when using the drug in a daily dose of 150 mg - abdominal pain, depression, dyspepsia, hematuria;

- very rarely (> 0.01% - <0,1%): vomiting, dry skin (with the use of the drug in a daily dose of 150 mg, dry skin is often observed), liver failure (the cause-and-effect relationship with bicalutamide is not established reliably).

With the simultaneous use of bicalutamide and GnRH analogues, the following adverse events with a frequency of> 1% can also be observed (the cause-effect relationship with the drug intake is not established, some of the noted side effects occurred in elderly patients):

From the cardiovascular system: heart failure.

From the digestive system: anorexia, dry mouth, indigestion, constipation, flatulence.

From the nervous system: dizziness, headache, insomnia, increased drowsiness.

Co of the respiratory system: dyspnea.

Co the side of the genitourinary system: sexual dysfunction, nocturia.

Co side of the hematopoietic system: anemia.

From the skin and its appendages: alopecia, 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.The general supportive therapy and control over the vital functions of the body are shown.

Interaction:

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

In studies in vitro shown, that (R) -enantiomer of bicalutamide is an inhibitor CYP 3A4, to a lesser extent affects the activity CYP 2С9, 2С19 and 2D6.

The potential for bicalutamide to interact with other drugs has not been revealed, however, when bicalutamide is used for 28 days against the background of the administration of midazolam, the area under the curve AUC Midazolam increased by 80%.

Incompatible with terfenadine, astemizole and cisapride.

Caution should be exercised in prescribing bicalutamide simultaneously with cyclosporine or calcium channel blockers. It may be necessary to reduce the dose of these drugs, especially when potentiating or developing unwanted reactions. After the beginning of use or elimination of bicalutamide, it is recommended that the concentration of cyclosporin in the blood plasma and the clinical condition of the patient be carefully monitored.

The simultaneous use of bicalutamide and drugs depressing microsomal oxidation of drugs, for example, with cimetidine or ketoconazole 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 anticoagulants coumarin series, warfarin (competition for the connection with proteins).

Special instructions:

Given the possibility of slowing the excretion of bicalutamide and its cumulation in patients with impaired 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.

In the case of pronounced changes in liver function, Bilumida® it is necessary to stop.

In patients with progression of the disease against a background of increased levels of prostate-specific antigen (PSA), consideration should be given to discontinuing Bilumide treatment®.

When appointing Bilumida® patients receiving anticoagulants of the coumarin series, it is recommended to monitor prothrombin time on a regular basis.

Taking into account the possibility of bicalutamide inhibition of cytochrome P450 (CYP 3A4), caution should be exercised with simultaneous administration of Bilumida® with preparations predominantly metabolized with the participation of CYP 3A4.

Patients with lactose intolerance should be informed that each Bilumida tablet® 50 mg contains 55.2 mg of lactose and a 150 mg tablet contains 165.6 mg of lactose.

Effect on the ability to drive transp. cf. and fur:Bilumide® does not affect the ability of patients to drive vehicles or engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Tablets coated with a coating, 50 mg and 150 mg.

Packaging:

Tablets of 50 mg, coated. For 7 or 10 tablets in a planar cell package. For 28 or 30 tablets in cans of orange glass. For 1 bank, 4 contour squares for 7 tablets, or 3 contour packs of 10 tablets together with instructions for use in a cardboard bundle.

Tablets of 150 mg, coated. For 7, 10 or 14 tablets in a planar cell pack. For 28 or 30 tablets in cans of orange glass. For 28 tablets in cans or bottles of polymer materials.For 28 tablets in a polymer can SC- a cover consisting of two parts: an external screw cap and an inner membrane with a ring to control the first opening or a polymer can with a shock absorber and a lid stretched with the control of the first opening. 1 bottle or bottle, 4 contour packs of 7 tablets each, or 3 contour packs of 10 tablets, or 2 contour packs of 14 tablets together with instructions for use in a cardboard pack.

Storage conditions:

At a temperature of no higher than 25 ° C in a dry, protected from light and out of reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-000723

Date of registration:03.08.2010

Expiration Date:Unlimited

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Representation: & nbspVEROPHARM, AO VEROPHARM, AO Russia

Information update date: & nbsp11.02.2017

Illustrated instructions

Instructions

Bilumide® (Bilumide®)