Casodex tablets 50mg, 28

CasodexЃ is prescribed for adult men (including the elderly) with advanced prostate cancer in combination with a GnRH analog or with surgical castration at a dose of 50 mg 1 time / day. Treatment should be started at the same time as the initiation of a GnRH analog or surgical castration.

Patients with impaired renal function and mild impaired liver function do not require dose adjustment. In patients with moderate and severe impairment of liver function, an increased cumulation of the drug may be observed.

Film-coated tablets

1 tab. bicalutamide

• simultaneous reception with terfenadine, astemizole, cisapride; hypersensitivity to bicalutamide and other components of the drug.

• CasodexЃ is not prescribed for women and children.

• CasodexЃ is used with caution in patients with impaired liver function, lactose intolerance, lactase deficiency and glucose / galactose malabsorption syndrome.

pharmachologic effect

Antiandrogenic non-steroidal drug. It is a racemic mixture, with antiandrogenic activity being predominantly (R) -enantiomer. The drug has no other types of endocrine activity. CasodexЃ binds to androgen receptors and, without activating gene expression, suppresses the stimulating effect of androgens. As a result, regression of prostate neoplasms occurs. In some patients, discontinuation of Casodex may lead to the development of a clinical antiandrogen withdrawal syndrome.

Pharmacokinetics

Suction

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. Concomitant food intake does not affect absorption.

Distribution

With a daily intake of Casodex at a dose of 50 mg of Css (R) -enantiomer in plasma, it is about 9 ?g / ml. At equilibrium, about 99% of all enantiomers circulating in the blood are the active (R) -enantiomer. With daily intake of Casodex, the concentration of the (R) -enantiomer in plasma increases by about 10 times due to prolonged T1 / 2, which allows Casodex to be taken 1 time / day. The connection with plasma proteins is high (for the racemic mixture 96%, for the (R) -enantiomer 99.6%).

Metabolism

It is extensively metabolized in the liver by oxidation and the formation of conjugates with glucuronic acid.

Withdrawal

Metabolites are excreted in urine and bile in approximately equal proportions. The (S) -enantiomer is excreted from the body much faster than the (R) -enantiomer, T1 / 2 of the last about 7 days.

Pharmacokinetics in special clinical situations

The pharmacokinetics of the (R) -enantiomer is not affected by age, impaired renal function, mild to moderate impairment of liver function. There is evidence that in patients with severe liver dysfunction, the elimination of the (R) -enantiomer from plasma slows down. In patients with moderate to severely impaired liver function, accumulation of bicalutamide in the body may be observed.

Side effect

CasodexЃ is well tolerated by most patients, and only in rare cases it has to be canceled due to side effects caused by it. The pharmacological action of Casodex can cause the following side effects. Very often (> 10%): gynecomastia (may persist even after stopping therapy, especially if the drug has been taken for a long time), breast tenderness, hot flashes. Often (? 1% - <10%): hot flashes *, anemia *, dizziness *, abdominal pain *, constipation *, nausea *, peripheral edema *, hematuria *, hepatotoxicity, transient elevated liver transaminases, cholestasis, and jaundice (the described changes in liver function were rarely assessed as serious, were transient in nature and completely disappeared or decreased, despite continued therapy or after discontinuation of the drug),decreased appetite, decreased libido, depression, drowsiness, dyspepsia, flatulence, alopecia, hirsutism or hair regrowth, dry skin, pruritus, erectile dysfunction, chest pain, weight gain. Rarely (? 0.1% - <1%): hypersensitivity reactions, angioedema, urticaria, interstitial pulmonary diseases (fatal cases reported), heart failure. Very rare (? 0.01% - <0.1%): hepatic failure (cases with a fatal outcome have been reported).interstitial lung disease (fatal cases reported), heart failure. Very rare (? 0.01% - <0.1%): hepatic failure (cases with a fatal outcome have been reported).interstitial lung disease (fatal cases reported), heart failure. Very rare (? 0.01% - <0.1%): hepatic failure (cases with a fatal outcome have been reported).

* With the simultaneous use of Casodex and GnRH analogues, the side effect was often observed.

Application during pregnancy and lactation

CasodexЃ is contraindicated in women and should not be administered to pregnant or lactating women.

Application for violations of liver function

No dose adjustment is required for patients with minor liver dysfunction. Casodex is used with caution in patients with impaired liver function. Considering the possibility of slowing down the elimination of bicalutamide and the accumulation of bicalutamide in patients with impaired liver function, it is advisable to periodically assess liver function

Application for impaired renal function

No dose adjustment is required in patients with impaired renal function.

Application in children

Casodex is not prescribed for children.

Use in elderly patients

Application is possible according to the dosage regimen.

special instructions

The drug is metabolized in the liver. Considering the possibility of slowing down the elimination of bicalutamide and the accumulation of bicalutamide in patients with severe liver dysfunction, it is advisable to periodically assess liver function. Most changes in liver function occur during the first 6 months of treatment with Casodex. CasodexЃ should be used with caution in patients with moderate to severe hepatic impairment. Severe liver dysfunctions with Casodex are rare (fatal cases have been reported). In case of development of pronounced changes in liver function, taking Casodex should be discontinued. In patients with progression of the disease against the background of increased levels of prostate-specific antigen (PSA), it is necessary to consider discontinuing treatment with Casodex.Considering the possibility of Casodex inhibition of the activity of cytochrome P450 (CYP3A4), caution should be exercised while administering Casodex with drugs that are mainly metabolized with the participation of CYP3A4. A decrease in glucose tolerance was observed in patients taking GnRH agonists. 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 CasodexЃ and GnRH agonists, it is necessary to monitor blood glucose concentrations. Influence on the ability to drive vehicles and control mechanisms When using Casodex, drowsiness and dizziness may occur, and therefore, care should be taken when driving vehicles or other moving mechanisms.A decrease in glucose tolerance was observed in patients taking GnRH agonists. 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 CasodexЃ and GnRH agonists, it is necessary to monitor blood glucose concentrations. Impact on the ability to drive vehicles and control mechanisms When using Casodex, drowsiness and dizziness may occur, and therefore, care should be taken when driving vehicles or other moving mechanisms.A decrease in glucose tolerance was observed in patients taking GnRH agonists. 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 CasodexЃ and GnRH agonists, it is necessary to monitor blood glucose concentrations. Impact on the ability to drive vehicles and control mechanisms When using Casodex, drowsiness and dizziness may occur, and therefore, care should be taken when driving vehicles or other moving mechanisms.it is necessary to control the concentration of glucose in the blood. Impact on the ability to drive vehicles and control mechanisms When using Casodex, drowsiness and dizziness may occur, and therefore, care should be taken when driving vehicles or other moving mechanisms.it is necessary to control the concentration of glucose in the blood. Impact on the ability to drive vehicles and control mechanisms When using Casodex, drowsiness and dizziness may occur, and therefore, care should be taken when driving vehicles or other moving mechanisms.

Overdose

Overdose cases in humans have not been described. There is no specific antidote, therefore, symptomatic therapy is carried out if necessary. Dialysis is ineffective because bicalutamide binds strongly to proteins and is not excreted unchanged in the urine. Shown is general supportive therapy and monitoring of vital body functions.

Drug interactions

There are no data on pharmacodynamic or pharmacokinetic interactions 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. In clinical studies using phenazone as a marker of cytochrome P450 activity, the potential ability of Casodex to interact with other drugs was not found. However, when using Casodex for 28 days while taking midazolam, the AUC of midazolam increased by 80%. The simultaneous use of Casodex with drugs such as terfenadine, astemizole and cisapride is contraindicated. Caution should be exercised when prescribing Casodex concomitantly with cyclosporine or slow calcium channel blockers. It may be necessary to reduce the dose of these drugs,especially in the case of potentiation or development of undesirable reactions. After starting the use or discontinuation of Casodex, it is recommended to carefully monitor the concentration of cyclosporine in the blood plasma and the clinical condition of the patient. Caution should be taken simultaneously with CasodexЃ and drugs that inhibit liver microsomal enzymes (for example, cimetidine, ketoconazole). The use of these combinations can lead to an increase in the concentration of bicalutamide in plasma and, possibly, to an increase in the incidence of adverse reactions. CasodexЃ enhances the effect of indirect coumarin anticoagulants (including warfarin), because can displace these drugs from their protein binding sites. It is recommended to regularly monitor the prothrombin time when prescribing Casodex to patientsreceiving indirect anticoagulants of the coumarin series.