Expiration date: 07/2027
Composition
1 film-coated tablet, 50.0 mg contains:
Active ingredient: bicalutamide 50.0 mg,
auxiliary substances (core): lactose monohydrate (milk sugar) 29.50 mg, microcrystalline cellulose 10.30 mg, sodium carboxymethyl starch 4.00 mg, povidone-K17 4.00 mg, magnesium stearate 0.70 mg, water 1.50 mg,
excipients (shell): hypromellose 1.65 mg, macrogol-4000 0.45 mg, titanium dioxide 0.90 mg.
1 film-coated tablet, 150.0 mg contains:
Active ingredient: bicalutamide 150.0 mg,
auxiliary substances (core): lactose monohydrate (milk sugar) 88.50 mg, microcrystalline cellulose 30.90 mg, sodium carboxymethyl starch 12.00 mg, povidone-K17 12.00 mg, magnesium stearate 2.10 mg, water 4.50 mg,
excipients (shell): hypromellose 4.95 mg, macrogol-4000 1.35 mg, titanium dioxide 2.70 mg.
Dosage form
film-coated tablets
Description
Round, biconvex, film-coated tablets of white or almost white color.
Pharmacodynamics
Bicalutamide is a racemic mixture with nonsteroidal antiandrogenic activity mainly of the (R)-enantiomer, and has no other endocrine activity. Bicalutamide binds to androgen receptors and, without activating gene expression, suppresses the stimulating effect of androgens on them. The result is a regression of prostate neoplasms.
In some patients, discontinuation of the drug may lead to the development of clinical antiandrogen withdrawal syndrome.
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 monotherapy or 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 monotherapy or adjuvant therapy compared with standard therapy (surgery, 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 monotherapy and as adjuvant treatment in combination with radiation therapy.
Pharmacokinetics
After oral administration, bicalutamide 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 (T1/2) of the latter is about 7 days.
With daily administration of bicalutamide, the concentration of the (R)-enantiomer in blood plasma increases approximately 10-fold due to prolonged T1 / 2, which makes it possible to take the drug 1 time per day.
With daily administration of bicalutamide at a dose of 50 mg, the steady-state concentration (Css) (R)-enantiomer in plasma is about 9 mcg / ml, at a dose of 150 mg - about 22 mcg / ml. At steady state, about 99% of all enantiomers circulating in the blood are active (R)-enantiomers.
Binding to plasma proteins is high (96% for the racemic mixture, 99.6% for the (R)-enantiomer). It is extensively metabolized in the liver (by oxidation and formation of conjugates with glucuronic acid). The metabolites are excreted by the kidneys and intestines in approximately equal proportions.
The average concentration of the (R)-enantiomer in the semen of men who received the drug at a dose of 150 mg is 4.9 micrograms/ml.
The pharmacokinetics of the (R)-enantiomer are not affected by age, impaired renal function, and mild to moderate hepatic impairment. There is evidence that plasma elimination of the (R)-enantiomer slows down in patients with severe hepatic impairment.
Indications for use
Bicalutamide 50.0 mg
In combination with an analogue of GnRH (gonadotropin-releasing hormone) or surgical castration for the treatment of advanced prostate cancer.
Bicalutamide 150.0 mg
As monotherapy or adjuvant therapy in combination with radical prostatectomy or radiation therapy in patients with locally advanced prostate cancer (T3-T4, any N, M0, T1-T2, N+, M0).
As monotherapy for the treatment of patients with locally advanced non-metastatic prostate cancer, when surgical castration or other medical interventions are not acceptable or applicable.
Contraindications
Cases of overdose in humans have not been described.
There is no specific antidote.
Overdose treatment: symptomatic, monitoring of vital body functions is necessary. Hemodialysis is ineffective because bicalutamide binds strongly to plasma proteins and is not excreted unchanged by the kidneys.
Use during pregnancy and lactation
Bicalutamide is contraindicated in women and should not be prescribed to pregnant and lactating mothers.
Side effects
The frequency of adverse reactions listed below was determined according to the following criteria: very common (at least 1/10), common (more than 1/100, less than 1/10), infrequent (more than 1/1000, less than 1/100), rare (more than 1/10000, less than 1/1000), very rare (less than 1/10000), including isolated reports.
Disorders of the immune system:
Rarely - hypersensitivity reactions, including angioedema, urticaria, skin rash.
Disorders of the endocrine system:
Very often - gynecomastia (may persist even after discontinuation of therapy, especially if the drug is taken for a long time), breast tenderness,
Often - decreased sexual desire, erectile dysfunction, weight gain, hyperglycemia.
Disorders of the nervous system:
Often - asthenia, headache, dizziness, insomnia or drowsiness, anxiety, decreased appetite,
Rarely - depression, flushes of blood to the face.
Disorders of the heart:
Often - myocardial infarction (fatal cases have been reported)*, development or aggravation of heart failure*, increased blood pressure.
Respiratory, thoracic, and mediastinal disorders:
Rarely - shortness of breath, chest pain, cough, pharyngitis, bronchitis, pneumonia, interstitial lung diseases (including fatal ones), rhinitis.
Disorders of the gastrointestinal tract:
Often - nausea,
Rarely - abdominal pain, dyspepsia, constipation, diarrhea, vomiting, flatulence.
Disorders of the liver and biliary tract:
Rarely - transient increase in liver transaminase activity, jaundice,
Very rarely - liver failure (including fatal).
Disorders of the skin and subcutaneous tissues:
Often - alopecia, hirsutism or restoration of hair growth, dry skin, skin itching. Musculoskeletal and connective tissue disorders,
Often - myasthenia gravis, myalgia, seizures, arthritis, joint contractures.
Disorders of the kidneys and urinary tract:
Infrequently - dysuria, polyuria, urinary retention, peripheral edema,
Rarely - hematuria.
General disorders and disorders at the injection site:
Often - fever, flu-like syndrome, chills, increased sweating, pelvic pain, infections.
Disorders of the blood and lymphatic system:
Often: anemia.
*have been observed in the treatment of prostate cancer in combination with a GnRH analogue. The risk of development increased with the simultaneous use of bicalutamide at a dose of 50 mg with an analog of GnRH. When bicalutamide was used at a dose of 150 mg as monotherapy for the treatment of prostate cancer, an increase in the incidence was not obvious.
Interaction
There are no data on pharmacokinetic or pharmacodynamic interactions between bicalutamide and GnRH analogues.
The (R)-enantiomer of bicalutamide is an inhibitor of the CYP3A4 isoenzyme, to a lesser extent affecting the activity of the CYP2C9, 2C19 and 2D6 isoenzymes. The potential ability of bicalutamide to interact with other drugs has not been found, however, when using the drug for 28 days while taking midazolam, the area under the concentration-time curve (AUC) of midazolam increases by 80%.
The inhibition of the CYP 3A4 isoenzyme by bicalutamide may be important when using drugs with a narrow therapeutic index that are metabolized in the liver. In this regard, the simultaneous use of bicalutamide with terfenadine, astemizole, 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 potentiation or the development of adverse reactions. After starting the use or discontinuation of bicalutamide, careful monitoring of cyclosporine plasma concentrations and the patient's clinical condition is recommended.
The simultaneous use of bicalutamide and drugs that inhibit microsomal oxidation of drugs, such as cimetidine or ketoconazole, may lead to an increase in the concentration of bicalutamide in plasma and, possibly, the frequency of side effects.
Enhances the effect of coumarin anticoagulants (warfarin).
Method of administration and dosage
Inside, regardless of the meal, drink enough liquid.
Adults and elderly men with advanced prostate cancer in combination with a GnRH analogue or surgical castration - 50 mg 1 time per day. Treatment with the drug should begin simultaneously with the start of taking the GnRH analogue or surgical castration.
Adults and elderly men with locally advanced prostate cancer - 150 mg 1 time per day. The drug should be taken for a long time, at least for 2 years. If signs of disease progression appear, the drug should be discontinued.
No dose adjustment is required in patients with impaired renal function or mild hepatic impairment. Increased accumulation of bicalutamide may occur in patients with moderate to severe hepatic impairment.
Overdose
Cases of overdose in humans have not been described.
There is no specific antidote.
Overdose treatment: symptomatic, monitoring of vital body functions is necessary. Hemodialysis is ineffective because bicalutamide binds strongly to plasma proteins and is not excreted unchanged by the kidneys.
Special instructions
Bicalutamide is extensively metabolized in the liver. Given the possibility of slowing the elimination of bicalutamide and accumulation of bicalutamide in patients with severe hepatic impairment, it is advisable to periodically evaluate liver function. Most changes in liver function occur during the first six months of treatment with the drug.
Bicalutamide should be used with caution in patients with moderate to severe hepatic impairment.
Severe liver disorders are rare when using the drug, and fatal cases have been reported. In case of marked changes in liver function and / or an increase in functional tests by more than 2 times, the drug should be discontinued.
When co-administered with cyclosporine, after the start of use or withdrawal of bicalutamide, careful monitoring of the concentration of cyclosporine in plasma and the patient's condition is recommended.
In patients with disease progression with increased prostate-specific antigen (PSA) concentrations, discontinuation of bicalutamide treatment should be considered.
Given the possibility of inhibition of cytochrome P450 activity by the drug (CYP 3A4 isoenzyme), caution should be exercised when using bicalutamide concomitantly with drugs primarily metabolized with the participation of the CYP 3A4 isoenzyme. It is recommended to regularly monitor prothrombin time when prescribing bicalutamide to patients receiving indirect coumarin anticoagulants.
In patients taking GnRH agonists, there was a decrease in glucose tolerance. 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.
Influence on the ability to drive motor vehicles and manage mechanisms
When using bicalutamide, drowsiness and dizziness may occur, and therefore caution should be exercised when driving vehicles or other moving mechanisms. If these side effects occur, you should refrain from performing these activities.
Form of release
Film-coated tablets, 50.0 mg and 150.0 mg.
Conditions of release from pharmacies
By prescription
Storage conditions
In a place protected from light, at a temperature not exceeding 25 C.
Keep out of reach of children.
Expiration date
3 years. Do not use the drug after the expiration date
