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

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 syndrome of "withdrawal" of antiandrogens.

When using bicalutamide in a daily dose of 150 mg daily for the treatment of patients with locally advanced (T3-T4, any N, M0; T1-T2, N+, M0) prostate cancer, as an immediate hormonal therapy or as an adjuvant therapy, significantly reduces the risk of progression of the disease and bone metastases. 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 in a dose of 150 mg as immediate therapy or adjuvant therapy, compared with standard therapy (surgical treatment, radiation therapy).

An increase in life expectancy among patients with locally advanced prostate cancer has been shown,who received bicalutamn at a dose of 150 mg as immediate monotherapy or adjuvant treatment in combination with radiotherapy.

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

With daily intake of bicalutamide, the 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 blood 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.

On the pharmacokinetics (R) -enantiomer does not affect age, impaired renal function, mild or moderate liver function disorder. There is evidence that in patients with severe degree of liver function impairment, elimination is slowed (R) -enantiomer from the blood plasma.

The association with blood 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 by the kidneys and intestines in approximately equal proportions.

Average concentration (R) -enantiomer in the semen of men who received bicalutamide and a dose of 150 mg, is 4.9 μg / ml.

Indications:

- Bicalutamide in a dose of 50 mg in combination with an analogue of GnRH (gonadotropin-releasing hormone) or surgical castration is indicated for the treatment of advanced prostate cancer;

- bicalutamide 150 mg is indicated for the treatment of locally advanced prostate cancer (T3-T4, any N, M0; T1-T2, N+, MO) as monotherapy or adjuvant therapy in combination with radical prostatectomy or radiotherapy;

- Bicalutamide 150 mg is also indicated for the treatment of locally advanced nonmetastatic prostate cancer in cases where surgical castration or other medical interventions are not acceptable or not suitable for the patient.

Contraindications:

- Hypersensitivity to bicalutamide or other components of the drug;

- simultaneous reception with terfenadine, astemizole and cisapride;

- bicalutamide should not be given to children and women.

Carefully:

- Violation of the function of the liver;

- lactose intolerance;

- deficiency of lactase and glucose-galactose malabsorption.

Pregnancy and lactation:

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

Dosing and Administration:

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 Bicalutamide should begin at the same time as the start of the GnRH analogue or surgical castration.

With locally advanced prostate cancer: inside by 150 mg once a day. Bicalutamide should be taken for a long time, at least for 2 years. If signs of disease progression appear, the drug should be discontinued.

Correction of the dosing regimen

Renal impairment

Correction of the dose is not required.

Dysfunction of the liver

With mild violations of liver function, dose adjustment is not required. In patients with moderate to severe hepatic impairment, an increased cumulation of bicalutamide may be observed (see section "Special instructions").

Side effects:

Bicalutamide is generally well tolerated. Only in rare cases, the use of bicalutamide is canceled because of side-effects caused by the drug. According to WHO recommendations, the side effects that can cause bicalutamideare classified according to the frequency of their development as follows: very often ≥ 10%, often ≥ 1% and <10%, infrequently ≥ 0.1% and <1%, rarely ≥ 0.01% and <0 , 1%, very rarely - <0.01%, is unknown (can not be estimated based on available data).

Below are the side effects that occurred with the use of bicalutamide 150 mg once a day and with simultaneous application of bicalutamide 50 mg once a day with analogues of GnRH.

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 (libido), depression.

Disturbances from the nervous system

Often: dizziness**;

often: drowsiness, headache *, paresthesia *, insomnia *, anxiety *.

Vascular disorders

Often: "hot flashes" **;

often: aphypertension.

Heart Disease

often: myocardial infarction (reported as fatal) *;

infrequently: heart failure.

Disorders from the gastrointestinal tract

Often: abdominal pain **, constipation **, nausea **, diarrhea *;

often: dyspepsia, flatulence, vomiting *.

Disturbances from the respiratory system, chest and mediastinal organs

Often: dyspnea;

often: increased cough *, pharyngitis *, bronchitis *, pneumonia *, rhinitis *;

infrequently: interstitial lung diseases (reported fatal cases) (postmarketing experience).

Disturbances from the liver and bile ducts

often: transient changes on the part of the liver (hepatotoxicity), incl. increased activity of "liver" transaminases, jaundice, increased activity of alkaline phosphatase * (described changes in liver function were rarely evaluated as serious, often transient, completely disappeared or decreased after drug withdrawal);

rarely: hepatic insufficiency (the cause-and-effect relationship with bicalutamide is not reliably established) (postmarketing experience).

Disturbances from the skin and subcutaneous tissues

Often: rash***;

often: alopecia, hirsutism / hair regrowth, dry skin, itchy skin, increased sweating *.

Disturbances from musculoskeletal and connective tissue

often: pain in the bones *, myasthenia gravis *, arthralgia *, arthritis *, back pain *, pathological fractures *.

Disturbances of the kidneys and bile ducts

Often: hematuria **, night urination to urinate *;

often: urinary tract infection *, frequent urination *, urinary retention *, urination disorder *, urinary incontinence *.

Violations of the genitals and mammary gland

Often: gynecomastia (can persist even after cessation of therapy, especially if the drug is taken for a long time) and tenderness of the mammary glands;

often: impotence / erectile dysfunction.

Disorders from the endocrine system

often: hyperglycemia *;

frequency is unknown: decrease in glucose tolerance (postmarketing experience) *.

Disorders from the metabolism and nutrition

Often: asthenia;

often: anorexia, weight gain, weight loss *.

General disorders and disorders at the site of administration

Often: chest pain **, peripheral edema **, pain *, pelvic pain *, infection *;

often: influenza-like syndrome *.

* These side effects were observed only with the simultaneous administration of bicalutamide (50 mg once daily) with analogues of GnRH.

** These side effects were observed with bicalutamide 150 mg once and the day was often, and not very often.

*** These side effects were observed with the simultaneous administration of bicalutamide (50 mg once daily) with GnRH analogues often, and not very often.

Overdose:

Cases of overdose in humans are not described. There is no specific antidote. Treatment is symptomatic. Dialysis is ineffective, because bicalutamide strongly binds to plasma proteins and is not excreted by the kidneys unchanged. It shows general supportive therapy and monitoring of vital body functions.

Interaction:

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

In studies in vitro shown, that (R) -enantiomer of bicalutamide is an isoenzyme inhibitor CYP3A4, and to a lesser extent affecting isoenzyme activity CYP 2C9, CYP 2C19 and CYP 2D6. In clinical studies using phenazone as a marker of cytochrome P450 activity (CYP) did not reveal the potential ability of bicalutamide to interact with other drugs, but with bicalutamide for 28 days against the medication of midazolam, the area under the concentration-time curve (AUC) of midazolam increased by 80%.

Contraindicated simultaneous use of bicalutamide with drugs such as terfenadine, astemizole and cisapride. Caution should be exercised in prescribing bicalutamide simultaneously with cyclosporine or blockers of "slow" calcium channels. It may be necessary to reduce the dose of these drugs, especially if side effects develop. After the beginning of the application or elimination of bicalutamide, it is recommended that the concentration of cyclosporin in the blood plasma and the clinical state of the patient be carefully monitored.

Caution should be exercised with simultaneous administration of bicalutamide and drugs depressing microsomal liver enzymes, for example, with cimetidine or ketoconazole,since their simultaneous application can lead to an increase in the concentration of bicalutamide in the blood plasma and, possibly, an increase in the incidence of side effects.

Bicalutamide enhances the effect of indirect anticoagulants coumarinovogo series, including warfarin, tk. competes with them for binding to proteins. It is recommended that prothrombin time be regularly monitored when bicalutamide is administered to patients receiving indirect coumarin anticoagulants.

Special instructions:

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.

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

Taking into account the possibility of bicalutamide inhibition of the activity of cytochrome P450 (isoenzyme CYP 3A4) caution should be exercised with the simultaneous administration of bicalutamide with drugs predominantly metabolized with the participation of the isoenzyme CYP 3A4 (see para.sections "Contraindications" and "Interaction with other medicinal products").

In patients taking GnRH agonists, a decrease in glucose tolerance was observed. This effect can lead to the development of diabetes mellitus or a decrease in tolerance to glucose in patients with diabetes mellitus. In connection with this, patients receiving bicalutamide in combination with GnRH agonists, it is necessary to monitor the concentration of glucose in the blood.

Patients with lactose intolerance should be informed that each 50 mg tablet of bicalutamide contains 61 mg of lactose monohydrate.

Use in patients with impaired hepatic function

Bicalutamide is extensively metabolized in the liver. Given the possibility of slowing the excretion of bicalutamide and cumulation of bicalutamide 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 treatment with bicalutamide.

Bicalutamide should be used with caution in patients with moderate to severe hepatic impairment.

Changes in liver function of severe degree with the use of bicalutamide occur rarely (see Fig.section "Side effect"), there are reports of cases with a fatal outcome.

In case of pronounced changes in liver function, bicalutamide should be discontinued.

Precautions for use

When handling the drug, special precautions are not required.

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

When using bicalutamide, drowsiness and dizziness may occur. When these undesirable phenomena appear, one should refrain from performing these activities.

Form release / dosage:

Tablets, film-coated, 50 mg.

Packaging:

For 14 tablets in a planar cell pack of aluminum foil and PVC film.

2 contour packs with instructions for use in a cardboard pack.

For 10 tablets in a planar cell pack of aluminum foil and PVC film.

3 contour packs with instructions for use in a cardboard pack.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002921

Date of registration:20.03.2015

Date of cancellation:2020-03-20

The owner of the registration certificate:BIOCAD, CJSC BIOCAD, CJSC Russia

Manufacturer: & nbsp

BIOCAD, CJSC Russia

Representation: & nbspBIOCAD CJSC BIOCAD CJSC Russia

Information update date: & nbsp21.11.2015

Illustrated instructions

Instructions

Bicalutamide (Bicalutamide)