Composition, form of production and packaging
The tablets covered with a film shell of white color, round, biconcave, with an engraved logo in the form of a rounded arrow on one side and "Casodex 150" on the other.
bicalutamide 150 mg
Excipients: lactose monohydrate - 183 mg, sodium carboxymethyl starch - 22.5 mg, povidone - 15 mg, magnesium stearate - 4.5 mg.
Sheath composition: hypromellose 7.5 mg, macrogol 300-1.5 mg, titanium dioxide (E171) 2.3 mg.
14 pcs. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
Antiandrogenic nonsteroid drug. It is a racemic mixture, with anti-androgenic activity predominantly possessing the (R) -enantiomer. The drug does not have other kinds of endocrine activity. Casodex В® binds to androgen receptors and, without activating the expression of genes, suppresses the stimulating effect of androgens. As a result, regression of prostate tumors occurs.
In some patients, discontinuing the use of Casodex can lead to the development of a clinical syndrome of anti-androgen withdrawal.
When Casodex is administered at 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 immediate hormonal therapy or as adjuvant therapy, 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 150 mg of Casodex В® as immediate therapy or adjuvant therapy compared to standard therapy (surgical treatment, radiation therapy).
An increase in life expectancy has been shown in patients with locally advanced prostate cancer who received CasodexВ® at a dose of 150 mg as immediate monotherapy and as an adjuvant treatment in combination with radiation therapy.
The use of Casodex at a dose of 150 mg compared with surgical castration in patients with locally advanced nonmetastatic prostate cancer did not reveal a statistically significant difference in life expectancy and time to progression with a statistically significant benefit of sexual function and physical condition.
After oral administration, it is quickly and completely absorbed from the digestive tract. Simultaneous food intake does not affect absorption.
With daily administration of Casodex, a dose of 150 mg of the C ss (R) enantiomer in plasma is about 22 Ојg / ml. At an equilibrium state, about 99% of all enantiomers circulating in the blood form the active (R) -enantiomer.
With the daily administration of Casodex, the concentration of the (R) enantiomer in the plasma increases by about 10 times due to prolonged T 1/2 , which allows us to take the Casodex 1 time / day.
The association with plasma proteins is high (for a racemic mixture of 96%, for the (R) -enantiomer of 99.6%).
The average concentration of the (R) -enantiomer in the semen of men receiving Casodex 150 mg is 4.9 Ојg / ml. The amount of bicalutamide that can potentially be detected in women after sexual intercourse is low and is about 0.3 Ојg / kg (this value is lower than required for changes in fetal development in laboratory animals).
Intensively metabolized in the liver by oxidation and the formation of conjugates with glucuronic acid.
Metabolites are excreted in urine and bile approximately in equal proportions.
(S) -enantiomer is eliminated from the body much faster (R) -enantiomer, T 1/2 of the latter about 7 days.
Pharmacokinetics in special clinical cases
The pharmacokinetics of the (R) -enantiomer are not affected by age, renal dysfunction, mild or moderate hepatic impairment.
There is evidence that in patients with severe impairment of liver function, the elimination of the (R) enantiomer from the plasma is slowed.
In patients with moderate and severe violations of liver function, cumulation of bicalutamide in the body can be observed.
- locally advanced prostate cancer as immediate monotherapy or as adjuvant therapy in combination with radical prostatectomy or radiation therapy;
- locally advanced non-metastatic prostate cancer as monotherapy in cases where surgical castration or other medical interventions are unacceptable or not applicable.
Casodex В® is prescribed for adults and elderly men in a dose of 150 mg 1 time / day. Kasodex В® should be taken for a long time, at least for 2 years. If signs of disease progression appear, the drug should be discontinued.
Patients with impaired renal function and with mild violations of liver function do not need dose adjustment.
In patients with moderate and severe impairment of liver function, an increased cumulation of the drug may be observed.
With the exception of specially specified cases, the incidence of side effects is calculated from the data of studies of monotherapy with Casodex В®, an early prostate cancer.
Very often (? 10%): gynecomastia (can persist even after discontinuation of therapy, especially in case of taking the drug for a long time), tenderness of the mammary glands, skin rash, asthenia.
Often (? 1% - <10%): depression, anorexia, dizziness, drowsiness, hot flashes, itching, abdominal pain, constipation, dyspepsia, flatulence, alopecia or hair regrowth, hirsutism, dry skin, hematuria, nausea, decreased sexual impulses, erectile dysfunction, chest pain, swelling, weight gain, increased hepatic transaminase activity, hepatotoxicity, jaundice, anemia, decreased appetite.
Infrequent (? 0.1% - <1%): hypersensitivity reactions, angioedema, hives, interstitial lung diseases (reported cases of fatal outcome) *.
Rarely (? 0.01% - <0.1%): liver failure (reported cases with fatal outcome). *
Increased activity of hepatic transaminases, cholestasis and jaundice have rarely been evaluated as serious, transient, completely disappearing or decreasing with continued therapy or after drug withdrawal. Very rarely on the background of bicalutamide, hepatic insufficiency developed, but the cause-and-effect relationship between the development of hepatic insufficiency and the treatment with Casodex was not reliably established.
* According to the post-marketing application of the drug.
- simultaneous administration with terfenadine, astemizole, cisapride;
- hypersensitivity to bicalutamide and other components of the drug;
Casodex В® is not prescribed for women and children.
CaudexВ® is used with caution in patients with impaired liver function, with lactose intolerance, lactase deficiency, and glucose / galactose malabsorption syndrome.
PREGNANCY AND LACTATION
Casodex В® is contraindicated in women and should not be given to pregnant women or during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function are not required to adjust the dose.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with minor violations of the function of the liver dose adjustment is not required. Caution is used with caution in patients with impaired hepatic function.Given the possibility of slowing the excretion of bicalutamide and cumulation of bicalutamide in patients with impaired hepatic function, it is advisable to periodically evaluate liver function
APPLICATION FOR CHILDREN
Casodex is not prescribed for children.
APPLICATION IN ELDERLY PATIENTS
The application is possible according to the dosing regimen.
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 Casodex.
In the case of development of pronounced changes in the function of the liver, Casodex should be discontinued.
In patients with progression of the disease against a background of increased levels of prostate-specific antigen (PSA), consideration should be given to discontinuing treatment with Casodex.
When appointing Casodex, patients receiving anticoagulants of the coumarin series are advised to regularly monitor prothrombin time.
Given the possibility of inhibition of cytochrome P450 (CYP3A4) activity by Casodex, Caution should be exercised while prescribing Casodex with drugs that are predominantly metabolized with CYP3A4.
Patients with lactose intolerance must be informed that each 150 mg Casodex tablet contains 183 mg of lactose monohydrate.
Impact on the ability to drive vehicles and manage mechanisms
When using Casodex, drowsiness and dizziness may occur, and care must be taken when driving vehicles or other moving mechanisms.
Cases of overdose in humans are not described. There is no specific antidote, so if necessary, symptomatic therapy is performed. Dialysis is ineffective, because bicalutamide binds firmly to proteins and is not excreted in the urine unchanged. It shows general supportive therapy and monitoring of vital body functions.
There is no data on the pharmacodynamic or pharmacokinetic interaction between Casodex and GnRH analogues.
In vitro studies have shown that the (R) -enantiomer of Casodex is an inhibitor of CYP3A4, to a lesser extent - CYP2C9, CYP2C19, CYP2D6. The potential capacity of Casodex to interact with other drugs has not been revealed. However, when Casodex was used for 28 days, midazolam AUC of midazolam increased by 80%.
Contraindicated simultaneous use of Casodex with such drugs as terfenadine, astemizole and cisapride.
Caution should be exercised in appointing Casodex along with cyclosporine or calcium channel blockers. It may be necessary to reduce the dose of these drugs, especially when potentiating or developing unwanted reactions. After the beginning of use or withdrawal of Casodex, it is recommended to carry out a careful monitoring of the concentration of cyclosporine in the blood plasma and the clinical state of the patient.
Simultaneous administration of Casodex and drugs depressing microsomal oxidation of drugs (cimetidine, ketoconazole) may lead to an increase in bicalutamide concentration in the plasma and, possibly, an increase in the incidence of undesirable reactions.
Kasodex В® enhances the effect of indirect anticoagulants coumarinovogo series (warfarin), tk. can displace these drugs from the sites of their binding to proteins.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 30 В° C. Shelf life - 4 years.