Casodex - instructions for use, doses, side effects, contraindications

Round, biconvex tablets of white color, covered with a film membrane; With the engraving of the logo in the form of a rounded arrow on one side and Casodex 150 - another.

Pharmacotherapeutic group:antitumor agent - antiandrogen

ATX: & nbsp

L.02.B.B.03 Bicalutamide

Pharmacodynamics:

Casodex® is a racemic mixture with non-steroidal antiandrogenic activity predominantly (R) -enantiomer, does not have a different endocrine activity.

Casodex® binds to androgen receptors and, without activating gene expression, suppresses the stimulating effect of androgens. The result is regression of malignant neoplasms of the prostate gland.

In some patients, discontinuation of Kasodex® may lead to the development of a clinical syndrome of "withdrawal" of anti-androgens.

When using Casodex® 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 an immediate hormonal therapy or as adjuvant therapy, significantly reduces the risk of progression of the disease and metastases in the bone.

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® as immediate therapy or adjuvant therapy compared to standard therapy (surgicalradiotherapy).

An increase in life expectancy among patients with locally advanced prostate cancer has been shown,Kasodeks® treated with a dose of 150 mg as immediate monotherapy or as adjuvant treatment in combination with radiotherapy.

Application Kasodeks® drug in a dose of 150 mg when compared with surgical castration in patients with locally advanced non-metastatic prostate cancer showed no statistically significant differences in survival and time to disease progression at a statistically significant advantage of sexual function and physical condition.

Pharmacokinetics:

After oral administration, it is quickly and completely absorbed from the gastrointestinal tract. Eating does not affect absorption.

(S) -enantiomer is eliminated much faster from the body (R) -enantiomer, the half-life of the latter is about 7 days.

With daily intake of bicalutamide, the concentration (R) -enantiomer in plasma increases approximately 10-fold due to a long half-life, which makes it possible to take the drug once a day.

With a daily intake of bicalutamide in a dose of 150 mg, the equilibrium concentration (R) enantiomer in plasma is about 22 μg / ml. At an equilibrium state, about 99% of all enantiomers circulating in the blood is active (R) -enantiomer.

On the pharmacokinetics (R) -enantiomer do not affect age, impaired renal function, mild and moderate impairment of liver function. There is evidence that in patients with severe impairment of liver function, elimination is slowed (R) -enantiomer from the plasma.

The association with plasma proteins is high (for a racemic mixture of 96%, for (R) -enantiomer 99.6%). 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.

Average concentration (R) -enantiomer in the semen of men receiving Casodex® 150 mg is 4.9 μg / ml. The amount of bicalutamide that can potentially be detected in women after sexual intercourse is low and is about 0.3 μg / kg (this value is lower than required for changes in fetal development in laboratory animals).

Indications:

- As immediate monotherapy or as adjuvant therapy in combination with radical prostatectomy or radiation therapy in patients with locally advanced prostate cancer;

- as a monotherapy for the treatment of patients with locally advanced nonmetastatic prostate cancer, when other medical interventions are unacceptable or not applicable.

Contraindications:

- Hypersensitivity to bicalutamide or other components of the drug;

- simultaneous reception with terfenadine, astemizole and cisapride;

- Casodex® should not be given to children or women.

Carefully:

- Impaired liver function;

- lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Pregnancy and lactation:

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

Dosing and Administration:

Adult men (including the elderly)): inside 150 mg once a day. Casodex® 150 mg should be taken for a long time, at least for 2 years.

If signs of disease progression appear, the drug should be discontinued.

Impaired renal function: correction of the dose is not required.

Dysfunction of the liver: with mild violations of the liver, dose adjustment is not required. In patients with moderate to severe hepatic impairment, an increased cumulation of Casodex® can occur.

Side effects:

Except where noted, the incidence of adverse events is calculated from the data of monotherapy with Casodex® 150 mg of early prostate cancer:

- 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 desire, erectile dysfunction, chest pain , oedema, weight gain, increased transaminase levels, hepatotoxicity, jaundice, anemia, decreased appetite.

- infrequently (≥0,1% - <1%): hypersensitivity reactions, including angioedema and urticaria, interstitial lung diseases (reported cases of fatal outcome) *.

- rarely (≥0,01 - <0,1%): photosensitivity reaction, hepatic insufficiency (reported cases with fatal outcome) *.

The transient increase in the activity of "liver" transaminases, cholestasis and jaundice has been rarely estimated as serious, transient, completely disappeared or decreased with continued therapy or after drug withdrawal.Very rarely bicalutamide treatment developed liver failure, but the causal relationship between the development of hepatic insufficiency and treatment with Kasodex® was not reliably established.

* According to the post-marketing application of the drug.

Overdose:

The case of overdose in humans is not described.

There is no specific antidote.

Treatment symptomatic. Dialysis is ineffective, because bicalutamide strongly binds to proteins and is not excreted in the urine unchanged. It shows general supportive therapy and monitoring of vital body functions.

Interaction:

Evidence of pharmacokinetic or pharmacodynamic interaction between Casodex® and GnRH analogues has not been obtained.

In studies in vitro shown, that (R) -enantiomer of bicalutamide is an isoenzyme inhibitor CYP 3A4, to a lesser extent affecting the activity of isoenzymes CYP 2С9, 2С19 and 2D6. The potential for the drug Casodex® to interact with other drugs has not been detected, but with the use of the preparation Casodex® for 28 days against the background of the administration of midazolam, the area under the concentration-time curve (AUC) midazolam increases by 80%.

Incompatible with terfenadine, astemizole, cisapride.

Caution should be exercised when using 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 the development of adverse reactions. After the application or discontinuation of the Kasodex® is recommended, careful monitoring of the plasma cyclosporine concentration and the clinical state of the patient is recommended.

The simultaneous use of the preparation of Kasodex® and drugs that inhibit microsomal liver enzymes, for example with cimetidine or ketoconazole, can lead to an increase in bicalutamide concentration in the plasma and, possibly, an increase in the incidence of side effects.

Strengthens the effect of indirect anticoagulants coumarinovogo number, including warfarin.

Special instructions:

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 six months of treatment with Casodex®.

In the case of pronounced changes in liver function, the use of Kasodex® should be discontinued.

In patients with progression of the disease against a background of increasing concentrations of prostate-specific antigen (PSA), consideration should be given to discontinuing the treatment with Casodex®.

When prescribing Casodex®, patients who receive anticoagulants of the coumarin series are advised to monitor prothrombin time on a regular basis.

Taking into account the possibility of inhibition of the activity of cytochrome P450 (isoenzyme) CYP 3A4), caution should be exercised while using the preparation Casodex® with preparations that are predominantly metabolized with the participation of the isoenzyme CYP 3A4.

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

It is recommended to regularly monitor prothrombin time when prescribing Casodex® to patients receiving indirect coumarinic anticoagulants.

Effect on the ability to drive transp.cf. and fur:

When using Kasodex®, drowsiness and dizziness may occur. In this connection, care should be taken when driving vehicles or other moving mechanisms.

Form release / dosage:

Tablets, film-coated, 150 mg.

Packaging:

14 tablets in a blister of Al / PVC; 2 blisters with instructions for use in a cardboard bundle with the control of the first autopsy.

Storage conditions:

At temperatures below 30 ° C, out of the reach of children.

Shelf life:

4 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013043 / 01

Date of registration:15.02.2011

The owner of the registration certificate:AstraZeneca UK LtdAstraZeneca UK Ltd United Kingdom

Manufacturer: & nbsp

CORDEN PHARMA, GmbH Germany

ASTRAZENECA UK, Ltd. United Kingdom

ZIO-HEALTH, JSC Russia

Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.

Information update date: & nbsp22.11.2015

Illustrated instructions

Instructions

Casodex® (Casodex®)