Description
Pharmacological action of
Pharmacotherapeutic group: Antitumor agent – antiandrogen
ATX:
L.02.BB03 Bicalutamide
Pharmacodynamics: Antitumor agent, non-steroidal antiandrogen drug – competitive antagonist. By binding to receptors on the surface of the cells of target organs, it makes them inaccessible to androgens, while increasing the concentration of hormones in the plasma. The result is a regression of prostate neoplasms.
The use of bicalutamide at a dose of 150 mg / day in patients with localized (T1-T2, N0 or NX, M0) or locally advanced (T3-T4, any N, M0 any T, N +, M0) prostate cancer reduces the risk of disease progression and relative risk of bone metastasis.
However, the effectiveness of bicalutamide with respect to survival rates is lower than that when performing surgical castration.
In some patients, discontinuation of treatment may lead to the development of antiandrogen withdrawal syndrome (after cancellation, 10-15% of patients have a temporary stabilization of the disease).
Pharmacokinetics: After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract (GIT) (food intake does not affect absorption). Communication with plasma proteins – 96-99%. It is intensively metabolized in the liver (by oxidation and the formation of conjugates with glucuronic acid) to inactive (S) – and active (R) -enantiomers. The time to reach maximum plasma concentration (TCmax) of the (R) -enantiomer is 31.3 hours.
(R) -enantiomer is excreted much faster than the (R) -enantiomer, the half-life (T1 / 2) of the latter is about 7 days. With a daily intake of bicalutamide at a dose of 150 mg / day, the equilibrium concentration in the blood plasma (Css) of the (R) enantiomer is 22 Ñg / ml. With Css, about 99% of all enantiomers circulating in the blood are the active (R) -enantiomer. With daily use, the concentration of (R) -enantiomer in plasma increases by about 10 times due to prolonged T1 / 2. It is excreted in the form of metabolites by the kidneys and with bile in equal proportions. The pharmacokinetics of the (R) -enantiomer does not depend on age, the state of renal function against the background of moderate hepatic impairment in patients with severe hepatic impairment, the elimination of the (R) -enantiomer from plasma slows down.
Indications
– Monotherapy or adjuvant therapy, in combination with an analogue of gonadotropin-releasing hormone (GnRH) or surgical castration, common prostate cancer
– treatment of locally advanced prostate cancer (T3-T4, any N, T2, T0, T1, T1, T1, T1, T1 , N +, M0) as monotherapy or adjuvant therapy in combination with radical prostatectomy or
radiotherapy – treatment of locally advanced non-metastatic prostate cancer in cases where surgical castration or other drugs are not effective or unacceptable.
Contraindications
– Hypersensitivity to bicalutamide or other components of the
preparation – lactase deficiency, lactose intolerance, glucose-galactose malabsorption
– women
– children
– simultaneous administration with terfenadine, astemizole and cisapride.
Precautions: In case of impaired liver function.
Use during pregnancy and lactation
Bicalutamide Canon is contraindicated in women and should not be prescribed to pregnant women or during lactation.
Special instructions
Bicalutamide is extensively metabolized in the liver. Given the possibility of slowing the elimination of bicalutamide and the cumulation of bicalutamide in patients with severe impaired liver function, 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 with the use of the drug are rare, fatal cases have been reported. In the case of the development of marked changes in liver function and / or increased functional tests more than 2 times, the drug should be discontinued.
When taken together with cyclosporine, after the start of use or cancellation of bicalutamide, it is recommended to carefully monitor the concentration of cyclosporine in the plasma and the patient’s condition.
In patients with disease progression amid an increase in the concentration of prostate-specific antigen (ASA), consideration should be given to discontinuing treatment with bicalutamide.
Given the possibility of inhibition by the drug of the activity of cytochrome P450 (CYP 3A4 isoenzyme), caution should be exercised while using bicalutamide with drugs, predominantly metabolized with the participation of the CYP 3A4 isoenzyme. It is recommended that prothrombin time be regularly monitored when prescribing bicalutamide to patients receiving indirect coumarin anticoagulants.
Patients taking GnRH agonists have 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. In this connection, in patients taking bicalutamide in combination with GnRH agonists, it is necessary to control the concentration of glucose in the blood.
Impact on the ability to drive transp. Wed and fur.: When using bicalutamide, drowsiness and dizziness may occur, and therefore caution should be exercised when driving vehicles or other moving mechanisms.
Composition
Active substance: bicalutamide 150 mg
excipients: corn starch ) 19.5 mg, lactose monohydrate (milk sugar) 132.9 mg, povidone 7.6 mg, sodium stearyl fumarate 3 mg
film composition: Opadry II white 12 mg, including: polyvinyl alcohol 4.8 mg, macrogol (polyethylene glycol) 2.424 mg, talc 1.776 mg, titanium dioxide 3 mg.
Dosage and administration
Adult men, including the elderly: For advanced prostate cancer in combination with a GnRH analog or surgical castration: 50 mg orally once a day.
For locally advanced prostate cancer: 150 mg orally once a day.
Bicalutamide should be taken continuously for at least 2 years.
If signs of disease progression appear, the drug should be discontinued.
Impaired renal function: Dose adjustment not required.
Impaired liver function: With mild impaired liver function, dose adjustment is not required. In patients with moderate to severe hepatic impairment, cumulation of the drug may be observed – dose adjustment is required.
Side effects
WHO classification of the incidence of side effects: very often -? 1/10 prescriptions (> 10%)
often – from 1/100 to <1/10 prescriptions (> 1% and < 10%) infrequently – from? 1/1000 to <1/100 appointments (> 0.1% and <1%) rarely – from? 1/10000 to <1/1000 appointments (> 0.01% and < 0.1%) very rare – <1/10000 prescriptions (<0.01%) Classification of unwanted adverse reactions according to damage to organs and organ systems (medical dictionary for regulatory activity Med-DRA) Violations from immune system: rarely – hypersensitivity reactions, including angioedema, urticaria, skin rash. Disorders from the endocrine system: very often – gynecomastia (can persist even after discontinuing therapy, especially if the drug is taken for a long time), breast tenderness often – decreased sex drive, erectile dysfunction, decreased or increased body weight, hyperglycemia, diabetes. Disorders of the nervous system: often – asthenic syndrome, dizziness, insomnia or drowsiness, anxiety, decreased appetite rarely – depression, flushing. Disorders of the heart: often – angina pectoris, development or worsening of heart failure, increased blood pressure. Disorders of the respiratory system, chest and mediastinal organs: rarely – chest pain, cough, pharyngitis, bronchitis, pneumonia, interstitial pulmonary disease (including fatal outcome), rhinitis. Disorders of the gastrointestinal tract: often – nausea rarely – abdominal pain, dyspepsia, constipation, diarrhea, vomiting, flatulence, gastric bleeding, dry oral mucosa. Disorders of the liver and biliary tract: rarely – a transient increase in the activity of hepatic transaminases, cholestasis, jaundice very rarely – liver failure (including with a fatal outcome). Disorders of the skin and subcutaneous tissues: often – alopecia, hirsutism or restoration of hair growth, dry skin. Violations of the musculoskeletal and connective tissue: often – myasthenia gravis, myalgia, cramps, 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. Laboratory and instrumental data: often: anemia. Drug Interactions There are no data on pharmacokinetic or pharmacodynamic interactions between bicalutamide and GnRH analogues. In vitro studies have shown that the (R) -enantiomer of bicalutamide inhibits CYP 3A4, to a lesser extent affect the activity of CYP 2C9, 2C19, 2D6 isoenzymes. In clinical studies using phenazone as a marker of the activity of cytochrome P450 (CYP), the drug s potential ability to interact with other drugs was not found, however, when using bicalutamide for 28 days while taking midazolam, the area under the concentration-time curve (AUC) of midazolam increased by 80%. The simultaneous use of bicalutamide with such drugs as terfenadine, astemizole and cisapride is contraindicated. Caution should be exercised when using bicalutamide simultaneously with cyclosporine, slow calcium channel blockers with drugs that inhibit microsomal liver enzymes, for example, with cimetidine or ketoconazole (a dose reduction of these drugs may be required). The simultaneous use can lead to an increase in the concentration of bicalutamide in plasma and, possibly, to an increase in the incidence of side effects. Enhances the effect of indirect coumarin anticoagulants, including warfarin (competition for protein binding). It is recommended that prothrombin time be regularly monitored when prescribing bicalutamide to patients receiving indirect coumarin anticoagulants. Overdose Cases of overdose in humans are not described. There is no specific antidote. Overdose treatment: symptomatic, monitoring of vital body functions is necessary. Hemodialysis is ineffective, since bicalutamide is firmly bound to plasma proteins and is not excreted unchanged in urine. Storage conditions In a dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children. Expiration 2 years. Deystvuyuschee substances Bykalutamyd Form of Treatment tablets