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

Active substance:	50 mg	150 mg
Bicalutamide	50.0 mg	150.0 mg
Excipients:
Lactose Monohydrate	62.7 mg	188.0 mg
Povidone K-25	5.0 mg	15.0 mg
Carboxymethyl starch of sodium (type A)	7.5 mg	22.5 mg
Magnesium stearate	1.5 mg	4.5 mg
Film Sheath:
Опадрай ОY-S-9622 * white	3.0 mg	8.0 mg
* Foam OY-S-9622 white consists of:
Hypromellose	2.57 mg	6.85 mg
Titanium dioxide	0.28 mg	0.74 mg
Propylene glycol	0.15 mg	0.41 mg

Description:

50 mg tablets: torifle, biconvex tablets, covered with a film shell of white color.

150 mg tablets: round, biconvex tablets, covered with a film shell of white color, with a risk.

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 and does not have other endocrine activity. Bicalutamide binds to androgen receptors and, without activating gene expression, suppresses androgenic activity. The result is a regression of prostate tumors. Termination of bicalutamide in some patients may lead to the development of a clinical syndrome of "withdrawal" of antiandrogens.

When bicalutamide is used in a daily dose of 150 mg daily for the treatment of patients with locally advanced (T3-T4, any N, M0 or any T, N+, M0) prostate cancer, as an adjuvant therapy, significantly reduces the risk of disease progression and metastasis in the bone.

With locally advanced prostate cancer, there has been a trend towards improved life expectancy without signs of disease progression in the groups of patients taking bicalutamide as immediate therapy or adjuvant therapy, compared with standard therapy (radical prostatectomy, radiation therapy).

Life expectancy was increased among patients with locally advanced prostate cancer with bicalutamide at a dose of 150 mg as immediate monotherapy and adjuvant treatment in combination with radiotherapy.

Pharmacokinetics:

Bicalutamide is rapidly and completely absorbed after ingestion. Food has no clinically significant effect on the bioavailability of the drug.

(S) -enantiomer is eliminated faster than (R) -enantiomer. The half-life (T_1/2) (R) -enantiomer from the blood plasma is about 1 week.

With prolonged use of bicalutamide, the maximum concentration (R) enantiomer in the blood plasma increases approximately 10 times, due to prolonged T_1/2, 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 blood plasma is about 9 μg / ml. When bicalutamide is used at a dose of 150 mg / day, the equilibrium concentration (R) -enantiomer is 22 μg / ml. Thanks to the long T_1/2, equilibrium concentration is reached approximately in 1 month after the beginning of therapy. 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 and does not change if renal function is impaired, mild or moderate liver function impairment. There is evidence that in patients with severe impairment of liver function, excretion (R) -enantiomer from the blood plasma is slowed down.

Bicalutamide is closely associated with plasma proteins (racemic mixture - 96%, (R) -enantiomer - more than 99%) and is actively metabolized (by oxidation and formation of conjugates with glucuronic acid). Metabolites are excreted by the kidneys and intestines approximately equally.

In the clinical study, the mean concentration (R) -enantiomer in the semen of men who received bicalutamide 150 mg / day, was 4.9 μg / ml.

Indications:

For a dose of 50 mg:

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

For a dose of 150 mg:

- Treatment of locally advanced prostate cancer (T3-T4, any N, M0, T1-T2, N +, M0) as immediate monotherapy or adjuvant therapy in combination with radical prostatectomy or radiation therapy.

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

Contraindications:

- Hypersensitivity to bicalutamide or other components of the drug;

- simultaneous application with terfenadine, astemizole and cisapride;

- Balutar® is not used in women and children.

Carefully:

Dysfunction of the liver, lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (preparation Balutar^® contains lactose).

Pregnancy and lactation:

The preparation Balutar® is not used in women, it is intended only for men.

Dosing and Administration:

Inside, regardless of food intake, once a day, drink a sufficient amount of liquid.

Adult men (including the elderly)

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

Treatment with Balutar® should be started at the same time as the beginning of the GnRH analogue or surgical castration.

With locally advanced prostate cancer: inside by 150 mg once a day. The drug Balutar® should be taken for a long time, at least for 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 Balutar^®.

Side effects:

Preparation Balutar^® in general, is well tolerated, only in rare cases, the drug is canceled because of the developed side effects.

Classification of the frequency of development of side effects of the World Health Organization (WHO):

very often -> 1/10

often from> 1/100 to <1/10

infrequently - from> 1/1000 to <1/100

rarely from> 1/10000 to <1/1000

very rarely - <1/10000

frequency is unknown - can not be estimated from the available data.

Side effects are presented in accordance with the Classification Med-DRA

Except for separately specified cases, the incidence of side effects is indicated by the results of clinical studies of monotherapy with Balutar® in a dose of 150 mg of locally advanced prostate cancer (T3-T4, any N, M0, T1-T2, N +, M0).

Classification by Med-DRA	Frequency of development of side effects	By-effect
Violations from the blood and lymphatic system:	Often	Anemia
Immune system disorders:	Infrequently:	Reactions hypersensitivity, including angioedema and urticaria;
Disorders from the metabolism and nutrition:	Often	Decreased appetite;
Disorders of the psyche:	Often	Decreased libido, depression;
Impaired nervous system:	Often	Dizziness, drowsiness;
Heart Disease:	Often	Myocardial infarction (reported cases of fatal outcome) *, heart failure *;
Vascular disorders:	Often:	Sensation of "tides";
Disturbances from the respiratory system, chest and mediastinal organs:	Infrequently:	Interstitial lung diseases (reported cases with fatal outcome);
Infringements from gastrointestinal tract:	Often:	Abdominal pain, constipation, indigestion, flatulence, nausea;
Disorders from the liver and bile ducts:	Often:	Hepatotoxicity , jaundice , increased activity of "hepatic" transaminases *;
Disorders from the liver and bile ducts:	Rarely:	Hepatic failure (reported cases with fatal outcome) *;
Disturbances from the skin and subcutaneous tissues:	Often:	Skin rash;
Disturbances from the skin and subcutaneous tissues:	Often:	Skin itching, dry skin, hirsutism / hair regrowth, alopecia;
Disorders from the kidneys and urinary tract:	Often:	Hematuria;
Violations of the genitals and breast:	Often:	Gynecomastia, tenderness of the mammary glands;
Violations of the genitals and breast:	Often:	Erectile disfunction;
General disorders and disorders at the site of administration:	Often	Asthenia
	Often	Pain in the chest, swelling;
Laboratory and instrumental data:	Often	Decreased body weight.

* Transient increase in the activity of "hepatic" transaminases, cholestasis and jaundice has been rarely estimated as serious, transient (transitory), completely disappeared or decreased with continued therapy or after drug withdrawal. In very rare cases, the development of hepatic insufficiency is described, but a cause-and-effect relationship with the use of bicalutamide is not established.

** Have been observed in the treatment of prostate cancer in combination with the GnRH analogue. The risk of developing increased with simultaneous application of bicalutamide in a dose of 50 mg with the analogue of GnRH. In the case of bicalutamide 150 mg as monotherapy for the treatment of prostate cancer, an increase in the frequency of development was not evident.

Side effects that were observed with the simultaneous use of bicalutamide in a dose of 50 mg and analogs of GnRH:

Violations of the blood and lymphatic system

very often: anemia;

very rarely: thrombocytopenia.

Disorders from the metabolism and nutrition:

often: diabetes, weight gain; infrequently: anorexia, weight loss, hyperglycemia.

Impaired nervous system:

very often: decreased libido;

often: dizziness, insomnia; infrequently: drowsiness.

Heart Disease:

very rarely: angina, conduction disturbance, including lengthening of intervals PR and QT on ECG, arrhythmias and nonspecific changes on the ECG.

Violation from the vessels:

very often: a sense of "tides";

often: hypertension.

Disturbances from the respiratory system, chest and mediastinal organs:

very often: dyspnea.

Disorders from the gastrointestinal tract:

very often: abdominal pain, diarrhea, constipation, nausea;

often: vomiting, increased activity of alkaline phosphatase;

infrequently: dryness of the oral mucosa, dyspepsia, flatulence.

Disturbances from the skin and subcutaneous tissues:

often: skin rash, hirsutism, increased sweating;

infrequently: alopecia.

Disorders from the kidneys and urinary tract:

very often: hematuria, nocturia.

Violations of the genitals and breast:

very often: erectile dysfunction, impotence.

General disorders and disorders at the site of administration:

very often: asthenia, infection;

very common: general pain, pelvic pain, back pain;

very often: peripheral edema;

often: chills, arthralgia;

infrequently: chest pain, headache, neck pain, flu-like syndrome.

Overdose:

Cases of overdose in humans are not described.

There is no specific antidote.

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

Interaction:

There is no data on the pharmacodynamic or pharmacokinetic interaction between bicalutamide and analogues of GnRH.

Research in vitro showed that (R) -enantiomer of bicalutamide inhibits isoenzyme CYP 3A4, to a lesser extent, affect the activity of isoenzymes CYP 2С9, 2С19 and 2D6. The degree of inhibition of this isoenzyme is not clinically significant for most drugs metabolized by cytochrome P450, However, with simultaneous application of bicalutamide from midazolam within 28 days the area under the curve "concentration-time" (AUC) of midazolam increased 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 connection with this simultaneous application of bicalutamide from terfenadine, astemisole and cisapride it is contraindicated.

Care should be taken when using bicalutamide simultaneously from cyclosporine and blockers of "slow" calcium channels. It may be necessary to reduce the dose of these drugs, especially in the case of potentiation or development of adverse events. After the beginning of bicalutamide application or after its cancellation it is recommended to apply ciclosporin under the control of its concentration in the blood plasma and the clinical state of the patient.

Simultaneously apply with drugs that inhibit microsomal liver enzymes, such as cimetidine and ketoconazole, Care 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 can displace an anticoagulant of indirect action (coumarin series), warfarin from the complex with blood plasma proteins, which leads to an increase in the effect of warfarin.

Special instructions:

The preparation Balutar® 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 advisable to periodically evaluate liver function. Most changes in liver function occur during the first 6 months of therapy.

In the case of severe liver function disorders, the drug should be discontinued. Considering the possibility of Balutar® inhibition of isoenzyme CYP 3A4, caution should be exercised when using simultaneously with preparations that are predominantly metabolized with the participation of an isoenzyme CYP 3A4.

With the progression of the disease against a background of increasing concentrations of prostate-specific antigen (PSA), it is necessary to consider the question of stopping the drug.

It is recommended that prothrombin time be regularly monitored with Balutar® in patients receiving indirect coumarin anticoagulants.

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

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

When the use of Balutar® can cause drowsiness and dizziness, and therefore care should be taken when driving vehicles or working with moving machinery. When drowsiness and dizziness occur, one should refrain from performing these activities.

Form release / dosage:

Film-coated tablets, 50 mg and 150 mg.

Packaging:

10 tablets are placed in a blister of the combined material PVC / PVDC and aluminum foil.

3 blisters are placed in a pack of cardboard along with instructions for use.

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 expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002117

Date of registration:02.07.2013

Expiration Date:02.07.2018

Date of cancellation:2018-04-12

The owner of the registration certificate:TAD Pharma GmbHTAD Pharma GmbH Germany

Manufacturer: & nbsp

Genepharm, S.A. Greece

TAD PHARMA, GmbH Germany

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp12.04.2018

Illustrated instructions

Instructions

Balutar® (Balutar®)