Bicalutamide pills 150mg, 30pcs – Pharmasyntez

Composition

1 tablet:

Active ingredient: bicalutamide 150 mg;

excipients:  lactose monohydrate 397 mg, povidone-K 30 10 mg, magnesium stearate 6 mg, sodium carboxymethyl starch 24 mg, colloidal silicon dioxide 3 mg;

film shell composition: Instacoat film coating 10 mg, hypromellose 4 mg, macrogol 2 g, talc 2 mg, titanium dioxide 2 mg

Pharmacological action

Pharmacotherapy group

Antitumor agent-antiandrogen

ATX code

L02BB03

Pharmacodynamics :

Bicalutamide is a racemic mixture with non-steroidal antiandrogenic activity mainly of the (R) – enantiomer and has no other endocrine activity. Bicalutamide binds to androgen receptors and suppresses the stimulating effect of androgens without activating gene expression. The result is a regression of malignant neoplasms of the prostate gland.

In some patients, discontinuation of bicalutamide may lead to the development of a clinical syndrome of” withdrawal ” of antiandrogens.

When bicalutamide is administered at a daily dose of 150 mg daily for the treatment of patients with locally advanced (T3-T4+ N M 0; T1-T2 N + M 0) prostate cancer as immediate hormone therapy or as adjuvant therapy, the risk of disease progression and bone metastases is significantly reduced. In locally advanced prostate cancer, there was a tendency to improve life expectancy without signs of disease progression in groups of patients taking bicalutamide at a dose of 150 mg as immediate therapy or adjuvant therapy compared to standard therapy (surgical treatment, radiation therapy).

An increase in life expectancy was shown among patients with locally advanced prostate cancer who received bicalutamide at a dose of 150 mg as immediate monotherapy or adjuvant treatment in combination with radiation therapy.

Pharmacokinetics:

After oral use, it is rapidly and completely absorbed from the gastrointestinal tract. Food intake does not affect absorption.

The (S)-enantiomer is eliminated from the body much faster than the (R) – enantiomer. The half-life of the latter is about 7 days.

With daily use of bicalutamide, the concentration of the (R)-enantiomer in blood plasma increases approximately 10 times due to a long half-life, which makes it possible to take the drug once a day.

When bicalutamide is taken daily at a dose of 50 mg, the steady-state concentration of the (R) – enantiomer in blood plasma is about 9 micrograms/ml. When taking 150 mg of bicalutamide daily, the steady-state concentration of the (R) – enantiomer is approximately 22 micrograms / ml. At steady state, about 99% of all enantiomers circulating in the blood are the active (R)-enantiomer.

The pharmacokinetics of the (R)-enantiomer are not affected by age renal impairment mild to moderate hepatic impairment. There is evidence that the elimination of the (R)-enantiomer from blood plasma slows down in patients with severe hepatic impairment.

The relationship with plasma proteins is high (96% for the racemic mixture and 996% for the (R) – enantiomer). It is intensively metabolized in the liver (by oxidation and formation of conjugates with glucuronic acid). Metabolites are excreted by the kidneys and intestines in approximately equal proportions.

The average concentration of the (R)-enantiomer in the semen of men treated with bicalutamide at a dose of 150 mg is 49 mcg / ml.

Indications

– bicalutamide at a dose of 150 mg is indicated for the treatment of locally advanced prostate cancer (T 3-T 4, any N M 0 T 1-T 2 N+ MO) as monotherapy or adjuvant therapy in combination with radical prostatectomy or radiation therapy;

– bicalutamide at a dose of 150 mg is also indicated for the treatment of locally advanced nemetallicheskih prostate cancer in the cases where surgical castration or other medical intervention is appropriate or not appropriate to the patient.

Use during pregnancy and lactation

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

Contraindications

-Hypersensitivity to bicalutamide or other components of the drug;

– concomitant use with terfenadine astemizole and cisapride;

– bicalutamide should not be prescribed to children and women.

With caution:

– Impaired liver function;

– lactose intolerance;

– lactase deficiency and glucose-galactose malabsorption.

Side effects

Bicalutamide is generally well tolerated. Only in rare cases, the use of bicalutamide is canceled due to side effects recognized by the drug. According to WHO recommendations, the side effects that bicalutamide can cause are classified according to the frequency of their development as follows: very common – ≥ 10% often – ≥ 1% and < 10% infrequently – ≥ 01% and < 1% rarely – ≥ 001% and < 01% very rare –

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

Disorders of the blood and lymphatic system

often: anemia.

Immune system disorders

infrequently: hypersensitivity reactions (including angioedema and urticaria*).

Mental disorders

are common: decreased sexual desire (libido) depression.

Nervous system disorders

very common: dizziness**;

often: drowsiness headache * Paresthesia* insomnia* anxiety*.

Vascular disorders

very common: hot flashes**;

often: arterial hypertension*.

Cardiac disorders

common: myocardial infarction (fatal cases have been reported)* ;

infrequently: heart failure.

Gastrointestinal disorders

very common: abdominal pain * * constipation* * nausea* * diarrhea*;

common: dyspepsia flatulence vomiting*.

Respiratory, thoracic, and mediastinal

disorders very common: shortness of breath;

common: increased coughing* pharyngitis* bronchitis* pneumonia* rhinitis*;

uncommon: interstitial lung disease (fatal cases reported) (post-marketing experience).

Violations of the liver and biliary tract

often: transient changes in the liver (hepatotoxicity), including increased activity of “liver” transaminases, jaundice increased activity of alkaline phosphatase* (described changes of liver function is rarely assessed as serious often were transient completely disappeared or decreased after drug withdrawal);

rare: hepatic failure (causal connection with the admission of bicalutamide significantly not installed) (post-marketing experience).

Skin and subcutaneous tissue disorders

are very common: rash***;

common: alopecia hirsutism / restoration of hair growth dry skin pruritus increased sweating*.

Musculoskeletal and connective tissue

disorders common: bone pain * myasthenia gravis* arthralgia* Arthritis* Back pain* abnormal fractures*.

Kidney and biliary tract

disorders very common: hematuria * * nocturnal urination*;

common: urinary tract infection* frequent urination* urinary retention* urinary disorders* urinary incontinence*.

Disorders of the genitals and breast

very often: gynecomastia (may persist even after discontinuation of therapy, especially if the drug is taken for a long time) and breast tenderness;

often: impotence/erectile dysfunction.

Endocrine disorders

common: hyperglycemia*;

frequency unknown: decreased glucose tolerance (post-marketing experience)*.

Metabolic and nutritional

disorders very common: asthenia;

often: anorexia weight gain weight loss*.

General disorders and disorders at the injection

site very often: chest pain* * peripheral edema* * pain* pelvic pain* infections*;

often: flu-like syndrome*.

* These side effects were observed only when bicalutamide (50 mg once a day) was co-administered with GnRH analogues.

* * These side effects were observed when bicalutamide was used 150 mg once a day and were often and not very often.

* * * These side effects were observed with concomitant use of bicalutamide (50 mg once a day) with GnRH analogues, but not very often.

Interaction

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

In vitro studies have shown that the (R)-enantiomer of bicalutamide is an inhibitor of the CYP3A4 isoenzyme and to a lesser extent affects the activity of the CYP 2C9, CYP 2C19 and CYP 2D6 isoenzymes. In clinical studies using phenazone as a marker of cytochrome P 450 (CYP) activity, bicalutamide was not found to interact with other drugs; however, when bicalutamide was used for 28 days while taking midazolam, the area under the concentration-time curve (AUC) of midazolam increased by 80%.

Concomitant use of bicalutamide with drugs such as terfenadine astemizole and cisapride is contraindicated. Caution should be exercised when prescribing bicalutamide concomitantly with cyclosporine or slow calcium channel blockers.It may be necessary to reduce the dose of these drugs, especially in case of side effects. After starting the use or discontinuation of bicalutamide, it is recommended to carefully monitor the concentration of cyclosporine in blood plasma and the patient’s clinical condition.

Caution should be exercised when concomitantly prescribing bicalutamide and drugs that inhibit microsomal liver enzymes for example with cimetidine or ketoconazole since their simultaneous use may lead to an increase in the concentration of bicalutamide in blood plasma and possibly to an increase in the frequency of side effects.

Bicalutamide enhances the action of indirect coumarin anticoagulants, including warfarin, because it competes with them for protein binding. It is recommended to regularly monitor prothrombin time when prescribing bicalutamide to patients receiving coumarin-type indirect anticoagulants.

How to take, course of use and dosage

Adult males (including the elderly)

For advanced prostate cancer in combination with an analog of GnRH or surgical castration: inside 50 mg once a day. Treatment with Bicalutamide should be started simultaneously with the start of taking the GnRH analog or surgical castration.

For locally advanced prostate cancer: inside 150 mg once a day. Bicalutamide should be taken continuously for at least 2 years. If there are signs of disease progression, the drug should be discontinued.

Correction of the dosage regimen

Impaired renal function

No dose adjustment is required.

Liver function disorders

No dose adjustment is required for mild hepatic impairment. Patients with moderate to severe hepatic impairment may experience increased accumulation of bicalutamide (see section “Special instructions”).

Overdose

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

Special instructions

Discontinuation of bicalutamide treatment should be considered in patients with progressive disease with elevated prostate-specific antigen (PSA) concentrations.

When prescribing bicalutamide to patients receiving coumarin-type anticoagulants, it is recommended to regularly monitor prothrombin time.

Given the possibility that bicalutamide may inhibit the activity of cytochrome P450 (the CYP 3A4 isoenzyme), caution should be exercised when prescribing bicalutamide concomitantly with drugs primarily metabolized with the participation of the CYP3A4 isoenzyme (see sections “Contraindications” and “Interaction with other drugs”).

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 glucose tolerance in patients with diabetes mellitus. Therefore, in patients taking 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 bicalutamide 50 mg tablet contains 61 mg of lactose monohydrate.

Use in patients with impaired liver function

Bicalutamide is extensively metabolized in the liver. Given the possibility of slowing the elimination of bicalutamide and accumulation 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 bicalutamide treatment.

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

Severe changes in liver function with bicalutamide are rare (see section “Side effects”). fatal cases have been reported.

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

Precautions for use

No special precautions are required when handling the product.

Influence on the ability to drive vehicles and mechanisms:

When using bicalutamide, drowsiness and dizziness may occur. If the described adverse events occur, you should refrain from performing these types of activities.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 30 °C.

Keep out of the reach of children.

Shelf

life is 4 years.

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

Active ingredient

Bicalutamide

Conditions of release from pharmacies

By prescription

Dosage form

Tablets