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

Active substance:
Bicalutamide	50.0 mg	150.0 mg
Excipients:
Magnesium aluminometasilicate	10.0 mg	30.0 mg
Sodium carboxymethyl starch	4.0 mg	12.0 mg
Magnesium stearate	2.0 mg	6.0 mg
Loudipress in terms of components	134.0 mg	402.0 mg
Lactose Monohydrate	124.6 mg	373.8 mg
Povidone	4.7 mg	14.1 mg
Crospovidone	4.7 mg	14.1 mg
Sheath:
Fallen II yellow 85F32771	8.0 mg	-
(polyvinyl alcohol 35.0-49.00%, talc 9.80-25.00%, macrogol 3350 7.35-35.20%, titanium dioxide and iron oxide yellow 15.15- 30.00%)
Fallen II yellow 85F32733	-	24.0 mg
(polyvinyl alcohol 35.0-49.00%, talc 9.80-25.00%, macrogol 3350 7.35-35.20%, titanium dioxide and iron oxide yellow 15.15- 30.00%)

Description:

Dosage 50 mg: oval tablet biconvex, covered with a film coating of light yellow color. On the cross-section the nucleus is white.

Dosage of 150 mg: rhomboid tablets biconvex form, covered with a film coating of yellow color. On the cross-section the nucleus is white.

Pharmacotherapeutic group:Antitumor agent - antiandrogen

ATX: & nbsp

L.02.B.B.03 Bicalutamide

Pharmacodynamics:

Bicalutamide is an antitumor agent, it is a racemic mixture with non-steroidal antiandrogenic activity predominantly (R) -enantiomer, does not have a different endocrine activity. Bicalutamide binds to androgen receptors on the surface of cells of target organs, suppresses the stimulating effect of androgens, without activating gene expression. As a result, the regression of malignant neoplasms of the prostate gland occurs. In some patients, discontinuing bicalutamide may lead to the development of a clinical syndrome of "withdrawal" of antiandrogens.

Pharmacokinetics:

Suction. After oral administration bicalutamide quickly and completely absorbed from the gastrointestinal tract. Eating does not affect the bioavailability of the drug. Time to reach the maximum concentration (TC_mOh) (R) -enantiomer was 31.3 hours.

Distribution. The association with plasma proteins is high (for a racemic mixture - 96%, for (R) enantiomer 99%).

Metabolism. Intensively metabolized in the liver (by oxidation and the formation of conjugates with glucuronic acid) to inactive (S) - and active (R) -enantiomers.

Excretion. Bicalutamide is excreted as metabolites by the kidneys and with bile in equal proportions. (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 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. When 150 mg of bicalutamide is taken daily, the equilibrium concentration (R) -enantiomer is about 22 μg / ml. At an equilibrium state, about 99% of all enantiomers circulating in the blood is active (R) -enantiomer.

Pharmacokinetics (R) -enantiomer is independent of age, renal function status, mild or moderate liver function disorder.

There is evidence that in patients with severe hepatic impairment, excretion is slowed (R) -enantiomer from the plasma.

Indications:

Prostate cancer:

- treatment of advanced prostate cancer in combination with an analogue of gonadotropin-releasing hormone (analogous to GnRH) or surgical castration;

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

- treatment of locally advanced, non-metastatic prostate cancer in cases where surgical castration or other medical interventions are unacceptable or not applicable.

Contraindications:

Hypersensitivity to bicalutamide or any other component of the drug.

Simultaneous reception of terfenadine, astemizole and cisapride.

Bicalutamide is contraindicated in children and women.

Carefully:

Lactose intolerance, lactase deficiency and glucose-galactose malabsorption (because the preparation contains lactose); abnormal liver function; simultaneous application of "slow" calcium channels with cyclosporine or blockers;simultaneous use with drugs that inhibit microsomal oxidation of drugs (cimetidine or ketoconazole).

Pregnancy and lactation:

The drug is contraindicated in women and should not be given to pregnant women or during breastfeeding.

Dosing and Administration:

Inside, regardless of food intake, with enough liquid.

The drug is given to older men (including the elderly).

With advanced prostate cancer - Inside of 50 mg once a day, in combination with simultaneous initiation of treatment with an analogue of GnRH or surgical castration.

With locally disseminated nonmetastatic prostate cancer - 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: patients with mild violations of liver function correction of the dose is not required. In patients with moderate or severe impairment of liver function, an increased cumulation of bicalutamide is possible, and therefore the drug should be used with caution.

Side effects:

Bicalutamide is well tolerated by most patients, and it is only rarely that it has to be canceled because of the development of side effects.

Side effects recorded more often than single observations are listed below for organs and systems, indicating the frequency of their occurrence.

Definition of frequency; very often (≥ 10%), often (≥ 1% and <10%), infrequently (≥ 0.1% and <1%), rarely (≥ 0.01% and <0.1%), very rarely <0.01%).

Infringements from bodies of a hemopoiesis: often - anemia*.

Disorders from the endocrine system: Often - gynecomastia (may persist after cessation of therapy, especially in case of taking the drug for a long time), tenderness of the mammary glands; often - decreased sexual desire, erectile dysfunction.

Impaired nervous system: Often - drowsiness; often - dizziness*.

Disorders from the psyche: often - when using the drug in a daily dose of 150 mg - depression.

Heart Disease: often - heart failure, myocardial infarction (reported cases with fatal outcome). The risk of complications from the heart arises when bicalutamide is used simultaneously with analogues of GnRH.

Disorders from the vascular system: often - hot flashes to the face.

Disorders from the gastrointestinal tract: Often - diarrhea; often - nausea *, abdominal pain *, constipation *, decreased appetite, indigestion, flatulence.

Disorders from the hepatobiliary system: often - hepatotoxicity, transient increase in the activity of "liver" transaminases, jaundice, cholestasis (described changes in liver function completely disappear or decrease with the continuation of therapy or after drug discontinuation); rarely - hepatic failure (reported cases with fatal outcome).

Disorders from the metabolism and nutrition: often - weight gain, anorexia.

Disturbances from the skin and subcutaneous tissues: Often - skin rash; often - itching; when the drug is used in a daily dose of 150 mg - alopecia, hair regrowth, hirsutism, dry skin.

Disturbances from the respiratory system, chest and mediastinal organs: often - chest pain; infrequently - interstitial lung diseases (reported cases with a fatal outcome).

Disorders from the kidneys and urinary tract: often hematuria.

Immune system disorders: infrequently - reactions of hypersensitivity, including angioedema and urticaria.

Common violations: Often - asthenia; often - peripheral edema.

* When taking the drug Bicane® in a dose of 50 mg in combination with GnRH analogs, a side effect was observed very often.

Overdose:

No cases of overdose have been reported in humans.

Treatment: there is no specific antidote, symptomatic therapy. Dialysis is ineffective, because bicalutamide strongly binds to plasma proteins and is not excreted by the kidneys in unchanged form. The general supportive therapy and control over the vital functions of the body are shown.

Interaction:

There are no data on the pharmacokinetic or pharmacodynamic interactions between bicalutamide and GnRH analogues.

In studies in vitro shown, that (R) - enantiomer of bicalutamide inhibits isoenzyme CYP 3A4, to a lesser extent affects the activity of isoenzymes CYP 2C9, CYP 2C19 and CYP 2D6. When bicalutamide is used for 28 days against the background of midazolam, the area under the kinetic curve "concentration-time" (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 and cisapride is contraindicated.

Care must be taken when bicalutamide is administered simultaneously with cyclosporine or blockers of "slow" calcium channels. In the case of increased effect or the development of side effects, a dose reduction of these drugs will be required. After initiation or discontinuation of bicalutamide therapy, it is recommended that the patient's clinical condition and cyclosporin concentration in the blood plasma be monitored. Simultaneously apply bicalutamide with drugs that depress microsomal oxidation of medicines, such as cimetidine and ketoconazoleCare should be taken with caution. it is possible to increase the concentration of bicalutamide in the blood plasma, which theoretically can lead to an increase in the incidence of side effects.

Bicalutamide enhances the effect of anticoagulants of the indirect action of the coumarin series, for example, warfarin (competition for binding to proteins).

Special instructions:

Bicalutamide is actively metabolized in the liver. Given the possibility of slowing the excretion of bicalutamide and its cumulation in patients with impaired liver function, it is necessary to periodically evaluate liver function (most liver function changes occur within the first 6 months of treatment). In case of severe liver disease, bicalutamide should be discontinued.

Given the possibility of inhibition of bicalutamide isoenzyme CYP 3A4, caution should be exercised when using simultaneously with preparations that are predominantly metabolized with the participation of an isoenzyme CYP 3A4.

When co-administered with cyclosporine, after the use or discontinuation of bicalutamide is started, careful monitoring of the patient's condition and monitoring of cyclosporin concentration in the plasma are recommended.

When bicalutamide is prescribed, patients receiving anticoagulants of the coumarin series are advised to regularly monitor prothrombin time.

With simultaneous use with GnRH agonists, a decrease in glucose tolerance is possible, which may be a manifestation of diabetes mellitus or a decrease in the level of glycemic control in case of an already existing diabetes mellitus.Therefore, the concentration of glucose in the serum should be monitored periodically.

In patients with lactose intolerance, adverse adverse reactions such as flatulence (bloating), abdominal pain, diarrhea, and rarely vomiting may develop. Patients with lactose intolerance should be informed that in each tablet Bicane® 50 mg contains 124.6 mg of lactose monohydrate, in a tablet Bicane® 150 mg - 373.8 mg lactose monohydrate.

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.

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

Care should be taken when driving vehicles and machinery, because Some of the side effects of the drug, such as asthenia, headache, dizziness and sleep disorders, can adversely affect the ability to perform work that requires increased concentration and speed of psychomotor reactions. If these side effects occur, you should refrain from performing these activities.

Form release / dosage:

Film-coated tablets, 50 mg and 150 mg.

Packaging:

By 7, 10 or 14 tablets in a contour cell packaging of polymer film and aluminum foil.

4 contour cell packs (7 tablets each), 3 contiguous cell packs (10 tablets each) or 2 contourcell packs (14 tablets each), along with instructions for use, are placed in a cardboard box.

For 28 or 30 tablets in polymer bottles, ukuporennyh plastic caps. A self-adhesive label is attached to the vial.

One bottle together with the instruction for use is placed in a cardboard box.

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 after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002486

Date of registration:04.06.2014

Date of cancellation:2019-06-04

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

Manufacturer: & nbsp

NATIVA, LLC Russia

Information update date: & nbsp21.11.2015

Illustrated instructions

Instructions

Bicane® (Bicana®)