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

core tablet: active substance: bicalutamide 50.00 mg; Excipients: lactose monohydrate 60.15 mg, sodium carboxymethyl starch 8.40 mg, povidone 7.98 mg, corn starch 11.80 mg, magnesium stearate 1.67 mg;

film sheath: Opadry Y1-18128 3.00 mg (contains methylcellulose 1.80 mg, titanium dioxide 0.90 mg, triacetin 0.30 mg).

Dosage of 150 mg

core tablet: active substance: bicalutamide 150.00 mg; Excipients: lactose monohydrate 200.66 mg, sodium carboxymethyl starch 16.55 mg, povidone 23.94 mg, corn starch 24.80 mg, magnesium stearate 4.05 mg;

film sheath: Opadry YS-1-7003 8.00 mg (contains hypromellose 4.78 mg, titanium dioxide 2.50 mg, macrogol 0.64 mg, polysorbate 80 0.08 mg)

Description:

White, round, biconvex tablets, covered with a film membrane.

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 on the surface of the cells of target organs without activating the expression of genes, thereby inhibiting the effect of androgens. The result is regression of prostate tumors.

In some patients, discontinuation of bicalutamide 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 ingestion quickly and completely absorbed from the gastrointestinal tract (regardless of food intake). The connection with plasma proteins is 96-99%. Intensively is 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 (R) -enantiomer was 31.3 parts.

(R) -enantiomer is displayed from the body much faster (R) -enantiomer, the half-life of the latter is about 7 days. With a daily intake of bicalutamide at a dose of 150 mg / day, the saturation concentrationR) -enantiomer in plasma is 22 μg / ml.

With daily intake of concentration (R) -enantiomer in plasma increases approximately 10-fold due to a long half-life.

Displayed in the form of metabolites by the kidneys and with bile in equal proportions. Pharmacokinetics (R) -enantiomer is independent of age, condition kidney function, against a background of mild liver function disorder; In patients with severe impairment of liver function, elimination is slowed down (R)- enantiomer from the plasma.

Indications:

- Monotherapy or as part of complex therapy before radical prostatectomy or radiation therapy in patients with locally advanced prostate cancer and a high probability of disease progressionBicalutamide Sandoz® in a dose of 150 mg).

- Treatment of patients with nonmetastatic locally advanced prostate cancer, in which other medical interventions are not appropriate or possible (Bicalutamide Sandoz® in a dose of 150 mg).

- Treatment of advanced prostate cancer in combination with an analogue of GnRH (gonadotropin-releasing hormone) or surgical castration (Bicalutamide Sandoz® in a dose of 50 mg).

Contraindications:

- Hypersensitivity to bicalutamide and other components of the drug;

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

- simultaneous reception with terfenadine, astemizole, cisapride;

- bicalutamide should not be assigned to women and children.

Carefully:

Hepatic insufficiency of moderate and severe severity, cardiovascular diseases, simultaneous use with drugs that extend the interval QT or causing the ventricular tachycardia such as "pirouette" (antiarrhythmic drugs class IA (eg, quinidine, disopyramide), Class III (for example, amiodarone, sotalol, dofetilide, ibutilide), methadone, moxifloxacin, neuroleptics, etc.)

Pregnancy and lactation:

This drug is not used in women.

Dosing and Administration:

Adult men (including the elderly)

With advanced prostate cancer in combination with an analogue of GnRH or surgical castration: inside, 50 mg once a day, regardless of food intake. Treatment should begin at the same time or 3 days before the start of the GnRH analogue or simultaneously with surgical castration.

With locally advanced prostate cancer: inside, 150 mg once a day, regardless of food intake. Treatment with drug Bicalutamide Sandoz® should be continuous, at least for 2 years. If signs of disease progression appear, the drug should be discontinued.

Dysfunction of the liver

In patients with mild violations of liver function, dose adjustment is not required. If the liver function of moderate and severe severity, there may be an increased cumulation of bicalutamide.

Renal impairment

In patients with impaired renal function, dose adjustment is not required.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development as follows: very often (≥1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, < 1/100), rarely (≥1 / 10000, <1/1000), very rarely (<1/10000), the frequency is unknown (can not be estimated based on available data).

When you receive bIcalutamide 150 mg once daily

Violations of the blood and lymphatic system

often: anemia.

Immune system disorders

infrequently: hypersensitivity reactions (including angioedema and urticaria).

Disorders of the psyche

often: decreased sexual desire, depression.

Violations from the nervous systems

often: dizziness, drowsiness.

Disorders from the cardiovascular system

often: "tides" of blood to the face;

frequency is unknown: elongation interval QT.

Disorders from the gastrointestinal tract

often: abdominal pain, constipation, indigestion, flatulence, nausea.

Disturbances from respiratory system, chest organs and the mediastinum

infrequently: interstitial lung diseases (reported cases with fatal outcome).

Disturbances from the liver and bile ducts

often: hepatotoxicity, transient changes in the liver, incl. increased activity of "liver" transaminases, jaundice (these changes in liver function were rarely estimated as serious, transient, completely disappeared or decreased with continued therapy or after withdrawal preparation);

rarely: hepatic insufficiency (including fatal outcome;the cause-and-effect relationship with the administration of bicalutamide is not reliably established).

Disturbances from the skin and subcutaneous tissue

Often: rash;

often: alopecia, hirsutism / hair regrowth, dry skin, itching;

rarely: reaction photosensitivity.

Disorders from the kidneys and urinary tract, pathways

often: hematuria.

Violations of the genitals and mammary gland

Often: gynecomastia and tenderness of the mammary glands;

often: impotence.

Disorders from the metabolism and nutrition

often: decreased appetite.

General disorders

Often: asthenia;

often: pain in the chest, swelling, weight gain.

With the simultaneous use of bicalutamide (50 mg once a day) and GnRH analogues

Violations of the blood and lymphatic system

Often: anemia.

Immune system disorders

infrequently: hypersensitivity reactions (including angioedema and urticaria).

Disorders of the psyche

often: decreased sexual desire, depression.

Disturbances from the nervous system

Often: dizziness; often: drowsiness.

Vascular disorders

Often: "tides" of blood to the face.

Heart Disease

often: myocardial infarction (reported cases of fatal outcome), cardiac failure;

frequency is unknown: elongation interval QT.

Violations with the sides of the digestive system

Often: abdominal pain, constipation, nausea;

often: dyspepsia, flatulence.

Disturbances from the respiratory system, chest and mediastinal organs

infrequently: interstitial lung diseases (reported cases with fatal outcome).

Disturbances from the liver and bile ducts

rarely: hepatic insufficiency (including fatal outcome, cause-and-effect relationship with bicalutamide is not reliably established).

Disturbances from the skin and subcutaneous tissue

often: rash, alopecia, hirsutism / hair regrowth, dry skin, itching;

rarely: reaction photosensitivity.

Disorders from the kidneys and urinary tract

Often: hematuria.

Violations of the genitals and mammary gland

Often: gynecomastia and tenderness of the mammary glands;

often: impotence.

Disorders from the endocrine system

frequency is unknown: decline tolerance to glucose (postmarketing experience).

Disorders from the metabolism and nutrition

often: decreased appetite.

General disorders

Often: asthenia, swelling;

often: pain in the chest, weight gain.

Overdose:

Until now, when taking bicalutamide, clinical signs of an overdose and the need for urgent medical interventions did not arise.

Treatment: symptomatic. There is no specific antidote. Dialysis is ineffective, because bicalutamide strongly binds to blood plasma proteins and is not excreted in the urine unchanged. It shows general supportive symptomatic therapy and monitoring of vital body functions.

Interaction:

(R) -bicalutamide is an inhibitor of the isoenzyme CYP 3A4 and has a weak inhibitory effect on the activity of isoenzymes CYP 2С9, 2С19 and 2D6. Clinical studies using antipyrine as a marker of cytochrome P450 activity (CYP) have not provided evidence of possible drug interaction with bicalutamide, but when applied bicalutamide for 28 days against the background of admission midazolam area under the curve "concentration-time" (AUC) Midazolam increases by 80%. For drugs with a low therapeutic index, this increase may be significant. In this regard, the simultaneous use of bicalutamide with terfenadine, astemizole and cisapride is contraindicated.

When co-administration of cyclosporine or blockers of "slow" calcium channels with bicalutamide, caution is necessary. It may be necessary to reduce the dose of these drugs, especially if there is an increase in the effect or the development of side effects. When cyclosporine is used after starting or stopping bicalutamide, careful monitoring of its plasma concentrations as well as the patient's condition is recommended.

When prescribing bicalutamide together with other drugs that can inhibit microsomal oxidation of drugs, for example, cimetidine and ketoconazole, caution should be exercised. In theory, it is possible to increase the concentration of bicalutamide in the blood plasma with the subsequent increase in the incidence of adverse reactions. Bicalutamide can replace the coumarin anticoagulant warfarin from the binding sites with proteins. Therefore, before beginning treatment with bicalutamide, patients already receiving anticoagulants of the coumarin series need careful monitoring prothrombin time.

Since with antiandrogen therapy, there is a risk of lengthening the interval QT, caution should be exercised with the simultaneous use of bicalutamide 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, etc.There is no data on the pharmacodynamic and pharmacokinetic interactions of bicalutamide with analogues of GnRH.

Special instructions:

Treatment with drug Bicalutamide Sandoz® should be performed under the control of the activity of "liver" transaminases in the blood. Most liver function changes occur within the first six months. Cases of death or hospitalization due to severe liver damage (hepatic insufficiency) have been documented in the postmarketing experience in connection with the use of bicalutamide. In case of pronounced changes in liver function, bicalutamide should be discontinued.

When using the drug Bicalutamide Sandoz® in patients receiving coumarinic anticoagulants is recommended to regularly monitor prothrombin time.

Given the potential for inhibition of cytochrome P450 (isoenzyme CYP3A4) activity by bicalutamide, caution should be exercised when concomitant administration of the drug Bicalutamide Sandoz^® with preparations predominantly metabolized with the participation of the CYP3A4 isoenzyme.

In patients receiving bicalutamide in combination with GnRH analogues, it is necessary to control the concentration of glucose in the blood.

In patients with progression of the disease against the background of an increase in prostate-specific antigen (PSA), consideration should be given to discontinuing drug treatment Bicalutamide Sandoz®.

With antiandrogen therapy, there is a risk of lengthening the interval QT. Before prescribing the drug Bicalutamide Sandoz® should carefully evaluate the relationship between the benefit and risk of ventricular pirouette tachycardia in patients with known risk factors for lengthening the interval QT or taking drugs that extend the interval QT (see section "Interaction with other medicinal products"). preparations ").

Special precautions for the destruction of unused medicinal product

There is no need for special precautions when destroying an unused preparation Bicalutamide Sandoz®.

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

During the treatment period, care should be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions due to the possibility of developing dizziness and drowsiness.

Form release / dosage:

Film-coated tablets, 50 mg and 150 mg.

Packaging:

For a dosage of 50 mg:

For 7 or 10 tablets in a blister of PVC / PVDC / Al or from PVC / Aclar/Al .

1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 blisters of 10 tablets are placed in a cardboard box together with instructions for medical use.

For 4 blisters of 7 tablets are placed in a cardboard box together with instructions for medical use.

For a dosage of 150 mg:

For 7 or 10 tablets in a blister of PVC / Aclar/Al.

For 4, 8 or 12 blisters, 7 tablets are placed in a cardboard box together with instructions for medical use.

1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 blisters of 10 tablets are placed in a cardboard box together with instructions for medical use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002032

Date of registration:22.03.2013 / 10.01.2014

Expiration Date:22.03.2018

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp25.01.2017

Illustrated instructions

Instructions

Bicalutamide Sandoz® (Bicalutamide Sandoz®)