Casodex, pills 150 mg, 28 pcs.

Composition

1 tablet contains:

Active ingredient:

bicalutamide 150 mg.

Auxiliary substances:

lactose monohydrate – 183 mg,

sodium carboxymethyl starch-22.5 mg,

povidone-15 mg,

magnesium stearate-4.5 mg.

Shell composition:

hypromellose – 7.5 mg,

macrogol 300-1.5 mg,

titanium dioxide (E 171) – 2.3 mg

. Pharmacological action

Pharmacodynamics

Antiandrogenic nonsteroidal drug. It is a racemic mixture, and the antiandrogenic activity is mainly due to the (R) – enantiomer. The drug does not have other types of endocrine activity. Casodex® binds to androgen receptors and, without activating gene expression, suppresses the stimulating effect of androgens. As a result, there is a regression of prostate neoplasms.

In some patients, discontinuation of Casodex may lead to the development of clinical antiandrogen withdrawal syndrome.

When using Casodex 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 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 the groups of patients taking Casodex ® 150 mg as immediate therapy or adjuvant therapy, compared with standard therapy (surgical treatment, radiation therapy).

An increase in life expectancy was shown among patients with locally advanced prostate cancer who received Casodex® at a dose of 150 mg as immediate monotherapy and as 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 non-metastatic prostate cancer did not reveal a statistically significant difference in life expectancy and time to progression, with a statistically significant advantage in sexual function and physical condition.

Pharmacokinetics

Suction

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

Distribution

When Casodex is taken daily at a dose of 150 mg, the C_ss (R) – enantiomer in plasma is about 22 micrograms/ml. At steady state, 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 approximately 10 times due to a long T_1/2, which allows you to take Casodex 1 time/day.

Plasma protein binding is high (96% for the racemic mixture,99.6% for the (R) – enantiomer).

The average concentration of the (R)-enantiomer in the semen of men treated with Casodex 150 mg is 4.9 micrograms / ml. The amount of bicalutamide that can potentially be detected in women after sexual intercourse is low and is approximately 0.3 mcg/kg (the value of this indicator is lower than required for changes in fetal development in laboratory animals).

Metabolism

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

Deduction

Metabolites are excreted in the urine and bile in approximately equal proportions. The (S) – enantiomer is eliminated from the body much faster than the (R) – enantiomer, T_1/2 of the latter is about 7 days.

Pharmacokinetics in special clinical cases

The pharmacokinetics of the (R)-enantiomer are not affected by age, renal impairment, or mild to moderate hepatic impairment.

There is evidence that in patients with severe hepatic impairment, the elimination of the (R)-enantiomer from plasma slows down.

Patients with moderate to severe hepatic impairment may experience accumulation of bicalutamide in the body.

Indications

• 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.

Use during pregnancy and lactation

Casodex® is contraindicated in women and should not be administered to pregnant women or during lactation.

Contraindications

• Concomitant use with terfenadine, astemizole, cisapride;
• hypersensitivity to bicalutamide and other components of the drug;
• Casodex® is not prescribed to women and children.

With caution: use Casodex® in patients with impaired liver function, lactose intolerance, lactase deficiency and glucose / galactose malabsorption syndrome.

Side effects

With the exception of specially specified cases, the frequency of side effects was calculated based on studies of monotherapy with Casodex® for early prostate cancer.

Very common (≥10%): gynecomastia (may persist even after discontinuation of therapy, especially if the drug is taken for a long time), breast tenderness, skin rash, asthenia.

Frequently (≥1%-

Infrequently (≥ 0.1%- *.

Rarely (≥ 0.01%- *

Increased hepatic transaminase activity, cholestasis, and jaundice were rarely assessed as serious, were transient in nature, and completely disappeared or decreased with continued therapy or after discontinuation of the drug. Very rarely, hepatic insufficiency developed while taking bicalutamide, but the causal relationship between the development of liver failure and treatment with Casodex has not been reliably established.

* – according to the data of post-marketing use of the drug.

Interaction

There are 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-of CYP2C9, CYP2C19, and CYP2D6. 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%.

Concomitant use of Casodex with drugs such as terfenadine, astemizole and cisapride is contraindicated.

Caution should be exercised when prescribing Casodex simultaneously with cyclosporine or calcium channel blockers. It may be necessary to reduce the dose of these drugs, especially in case of potentiation or development of adverse reactions. After starting to use or discontinuing Casodex, it is recommended to carefully monitor the concentration of cyclosporine in blood plasma and the patient’s clinical condition.

Concomitant administration of Casodex and drugs that inhibit microsomal oxidation of drugs (cimetidine, ketoconazole) may lead to an increase in the concentration of bicalutamide in plasma and, possibly, to an increase in the frequency of adverse reactions.

Casodex ® enhances the effect of indirect coumarin anticoagulants (warfarin), as it can displace these drugs from the sites of their binding to proteins.

How to take, course of administration and dosage

Casodex® is prescribed to adults and elderly men at a dose of 150 mg 1 time / day. Casodex® should be taken for a long time, at least for 2 years. If there are signs of disease progression, the drug should be discontinued.

In patients with impaired renal function and mild hepatic impairment, no dose adjustment is required.

Patients with moderate to severe hepatic impairment may experience increased accumulation of the drug.

Overdose

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 strongly to proteins and is not excreted unchanged in the urine.

General maintenance therapy and monitoring of vital body functions are indicated.

Special instructions

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 treatment with Casodex.

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

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

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

Given the possibility of Casodex inhibiting the activity of cytochrome P450 (CYP3A4), caution should be exercised when concomitantly prescribing Casodex with drugs that are mainly metabolized with the participation of CYP3A4.

Patients with lactose intolerance should be informed that each 150 mg Casodex tablet contains 183 mg of lactose monohydrate.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

When using Casodex, drowsiness and dizziness may occur, and therefore caution should be exercised when driving vehicles or other moving mechanisms.

Form of production

Coated tablets.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

4 years

Active ingredient

Bicalutamide

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Weight

Weight: 22 gr.