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

	Tablet 50 mg	Tablet 150 mg
Active substance:
bicalutamide	50 mg	150 mg
Excipients:
lactose monohydrate (milk sugar)	55.7 mg	167.1 mg
potato starch	30.8 mg	92.4 mg
microcrystalline cellulose	8 mg	24 mg
Primogen (sodium carboxymethyl starch)	4.8 mg	14.4 mg
povidone (polyvinylpyrrolidone)	8.0 mg	24.0 mg
magnesium stearate	1.6 mg	4.8 mg
silicon dioxide colloid (aerosil)	1.1 mg	3.3 mg
Shell:
hypromellose (hydroxypropylmethylcellulose)	2, 15 mg	6.45 mg
povidone (polyvinylpyrrolidone)	1.35 mg	4.05 mg
polysorbate (Tween 80)	0.45 mg	1.35 mg
talc	0.6 mg	1.8 mg
titanium dioxide	0.4 mg	1.2 mg
dye quinoline yellow (E 104)	0.05 mg	0.15 mg

Description:The tablets covered with a film cover of yellow color, round, biconcave.On the cross-section, two layers are visible, the inner layer is white or almost white.

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 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, the half-life of the latter is about 7 days.

With daily intake of bicalutamide, the equilibrium concentration (R) -enantiomer in blood 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 50 mg, the equilibrium concentration (R) -enantiomer in plasma is about 9 μg / ml, when taken at a dose of 150 mg - about22 μg / ml. At an equilibrium state, 99% of all enantiomers circulating in the blood is active (R) -enantiomer.

Pharmacokinetics (R) -enantiomer is independent of age, impaired renal function, impaired liver function (mild or moderate). There is evidence that in patients with severe impairment of liver function, elimination (R) -enantiomer from the plasma is slowed down.

Connectivity from plasma proteins 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.

Indications:

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

- 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;

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

Contraindications:

- Hypersensitivity to bicalutamide or any other components of the drug;

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

- simultaneous reception with terfenadine, astemizole and cisapride.

- Bilumide® should not be assigned to women and children.

Carefully:

- If the liver function of moderate and severe severity;

- In patients with known risk factors for lengthening the interval QT or taking drugs that extend the interval QT;

- when used simultaneously with: cyclosporine; blockers of "slow" calcium channels; drugs that inhibit microsomal oxidation of drugs (cimetidine and ketoconazole); drugs predominantly metabolized with the participation of isoenzyme CYP3A4;

- with a deficiency of lactase, lactose intolerance;

- with glucose-galactose malabsorption.

Pregnancy and lactation:

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

Dosing and Administration:

Adults and older men:

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

Treatment - 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 of 150 mg (1 tablet of 150 mg or 3 tablets of 50 mg) once a day. Bilumide® should be taken long, at least for 2 years. When signs of progression appear the drug should be discontinued.

Renal impairment: correction of the dose is not required.

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

Side effects:

Side effects arising from the application of bicalutamide - tablets coated with a film coat, 50 mg:

- very often (≥1 / 10): anemia, gynecomastia (can persist even after cessation of therapy, especially in case of taking the drug for a long time), tenderness of the mammary glands, asthenia, rash;

- often (≥1 / 100 - <1/10): "hot flashes", anemia *, dizziness *, abdominal pain *, constipation *, nausea *, puffiness *, hematuria *, hepatotoxicity, transient increase in activity of "liver" transaminases, jaundice (described changes in liver function were rarely evaluated as serious, often transient, completely disappeared or decreased with continued therapy or after withdrawal of the drug), decreased appetite, decreased libido, depression, drowsiness, dyspepsia, flatulence, alopecia, hirsutism or hair regrowth, dry skin, itchy skin, erectile dysfunction, chest pain, weight gain, myocardial infarction (reported fatal cases) **, heart failure **, lengthening of the interval QT;

- rarely (≥1 / 10,000 - <1/1 000): reactions hypersensitivity, angioneurotic edema, urticaria, interstitial lung diseases (reported fatal cases), photosensitivity reactions **;

- very rarely (≤1 / 10,000): hepatic insufficiency (reported cases with fatal outcome).

* When taking the drug in combination with the analogues of gonadotropin-releasing hormone (GnRH), the side effect was observed very often.

** A side effect was observed when taking the drug.

Side effects arising from the use of bicalutamide - tablets coated with a film coating, 150 mg:

- very often (≥1 / 10): gynecomastia (may persist even after discontinuation of therapy, especially if the drug is taken for a long time), tenderness of the mammary glands, skin rash, asthenia;

- often (≥1 / 100 - <1/10): depression, anorexia, dizziness, drowsiness, hot flashes, itching, abdominal pain, constipation, dyspepsia, flatulence, alopecia or hair regrowth / hirsutism, decreased sexual desire, erectile dysfunction, chest pain, swelling, weight gain, increased transaminase activity , hepatotoxicity, jaundice, anemia, decreased appetite;

- infrequently (≥1 / 1,000 - <1/100): hypersensitivity reactions, including angioedema and hives, interstitial lung diseases (reported fatal cases);

- rarely (≥1 / 10,000 - <1/1 000): Photosensitivity reactions, liver failure (reported cases with fatal outcome) *.

Transient increase in the activity of "liver" transaminases,cholestasis and jaundice were rarely evaluated as serious, transient in nature, completely disappeared or decreased with continued therapy or after drug withdrawal. Very rarely on the background of treatment with bicalutamide, hepatic insufficiency developed, but the cause-and-effect relationship between the development of hepatic insufficiency and treatment with the drug was not established reliably.

* According to the post-registration application of bicalutamide.

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 it has been shown that the (R) -enantiomer of bicalutamide is an inhibitor of CYP3A4, to a lesser extent affects the activity of CYP2C9, CYP2C19 and CYP2D6.

Potential ability of bicalutamide to interact with other medicinalno drugs were found, however, when bicalutamide was used for 28 days against the background of midazolam, the area under the midazolam AUC curve increased by 80%.

Not compatible 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 in case of potentiation or development of 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).

Since with antiandrogen therapy, there is a risk of lengthening the interval QT, caution should be exercised when using bicalutamide simultaneously with drugs that cause lengthening of the interval QT or drugs capable of inducing ventricular tachycardia such as pirouettes, such as antiarrhythmic drugs of the class IA (eg, quinidine, disopyramide), Class III (for example, amiodarone, sotalol, dofetilide, ibutilide), methadone, moxifloxacin, neuroleptics and other

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 case of pronounced changes in liver function, taking Bilumide® should be stopped.

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

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

Given the potential for inhibition of cytochrome P450 (CYP3A4) activity by bicalutamide, caution should be exercised while concomitant administration of Bilumide® with drugs predominantly metabolized with CYP3A4.

With antiandrogen therapy, there is a risk of prolonging the QT interval. Prior to the appointment of the drug should carefully evaluate the relationship between the benefits and risk of ventricular tachycardia such as "pirouette" in patients with known risk factors for prolonging the QT interval or taking drugs that extend the QT interval.

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:Film-coated tablets, 50 mg and 150 mg.

Packaging:

For 7, 10 or 14 tablets in a contour mesh package.

For 28 tablets in a jar of polymer materials.

Each jar or 4 contour squeezed packs of 7 tablets, or 3 contour packs of 10 tablets,or 2 contour packs of 14 tablets together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

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

Terms of leave from pharmacies:On prescription

Registration number:P N003218 / 01

Date of registration:19.12.2008 / 09.10.2015

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: & nbsp05.04.2017

Illustrated instructions

Instructions

Bilumide® (Bilumide®)