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

Round, biconvex tablets, covered with a film shell of white color, with engraving of the logo in the form of a rounded arrow on one side and Cdx - 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 endocryna 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.

Pharmacokinetics:

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

(S) -enantiomer is eliminated from the body much faster (R) -enantiomer, half-life of the latter - 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 50 mg, the equilibrium concentration (R) -enantiomer is about 9 μg / ml. When 150 mg of bicalutamide is taken daily, the equilibrium concentration (R) -enantiomer 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.

Indications:

- Casodex® in a dose of 50 mg in combination with an analogue of GnRH (gonadotropin-releasing hormone) or surgical castration is indicated for the treatment of advanced prostate cancer;

- Casodex® in a dose of 150 mg is indicated for the treatment of locally advanced prostate cancer (T3-T4, any N, M0; T1-T2, N+, M0) as monotherapy or adjuvant therapy in combination with radical prostatectomy or radiotherapy;

- Casodex® in a dose of 150 mg is also indicated for the treatment of locally advanced,nonmetastatic prostate cancer in cases where surgical castration or other medical interventions are unacceptable or unsuitable for the patient

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):

With advanced prostate cancer in combination with an analogue of GnRH or surgical castration: inside by 50 mg once a day. Treatment with Casodex® should be started at the same time as the beginning of the GnRH analogue or surgical castration.

When locally advanced prostate cancer: inside by 150 mg once a day. Casodex® should be taken for a long time, at least for 2 years.

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

Renal impairment: dose adjustment is not required.

Hhepatic function: with a mild violation of liver function correction of the dose is not required. In patients with moderate to severe hepatic impairment, increased cumulation of Casodex® can be observed (see section "Special instructions").

Side effects:

Casodex®, in general, is well tolerated, only in rare cases the drug is canceled because of the side effects caused.

The pharmacological action of bicalutamide can cause the following side effects;

- very often (> 10%): gynecomastia (may persist even after discontinuation of therapy, especially in case of taking the drug for a long time), tenderness of the mammary glands, asthenia, rash.

- often (≥1% - <10%): "Hot flashes" *, anemia *, dizziness *, abdominal pain *, constipation *, nausea *, peripheral edema *, hematuria *, hepatotoxicity, transient increase in the activity of "liver" transaminases, jaundice (described changes in liver function were rarely evaluated as serious, often transient,completely disappeared or decreased with continued treatment or after discontinuation of the drug), decreased appetite, decreased libido, depression, somnolence, dyspepsia, flatulence, alopecia, hirsutism, and hair regrowth, dry skin, itchy skin, erectile dysfunction, chest pain, weight increase body, myocardial infarction (reported cases of fatal outcome) **, heart failure **.

- rarely (≥0.1% - <1%): reactions hypersensitivity, angioneurotic edema, urticaria, interstitial lung diseases (reported cases with fatal outcome), photosensitivity reaction **.

- rarely (≥0,01% - <0,1 %): hepatic failure (reported cases with fatal outcome).

* When taking the drug Kasodex® at a dose of 50 mg in combination with GnRH analogs, a side effect was observed very often.

** A side effect was observed with a 50 mg dose of Kasodex® in combination with GnRH analogues.

Overdose:

Cases of overdose in humans are not described.

There is no specific antidote, the treatment is 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, affect the activity of isoenzymes CYP 2С9, 2С19 and 2D6. In clinical studies using phenazone as a marker of cytochrome P450 (CYP) activity, the potential ability of Casodex® to interact with other drugs has not been detected, however, with the use of Casodex® for 28 days against midazolam, the area under the concentration curve -time "(AUC) of midazolam increased by 80%.

Contraindicated concurrent use of the drug Casodex ® with drugs such as terfenadine, astemizole and cisapride.

Caution should be exercised when using Casodex® simultaneously with cyclosporine or blockers of "slow" calcium channels.It may be necessary to reduce the dose of these drugs, especially if side effects develop. 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.

Be cautious when using Kasodex® and drugs that inhibit microsomal liver enzymes, for example, with cimetidine or ketoconazole. Simultaneous application 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 (competition for communication with proteins). It is recommended to regularly monitor prothrombin time when prescribing Casodex® to patients receiving indirect coumarinic anticoagulants.

Special instructions:

Kasodex® is extensively metabolized in the liver. Given the possibility of slowing down excretion of bicalutamide and accumulation of bicalutamide in patients with severe hepatic impairment, it is advisable to periodically assess liver function.Most changes in liver function occur during the first six months of treatment with Casodex®.

Casodex® should be used with caution in patients with moderate to severe hepatic impairment.

Severe hepatic changes with the use of the drug Casodex ® are rare (see section "Side effect"), reported cases with fatal outcome.

In the case of development of pronounced changes in liver function, the administration 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®.

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 (see "Contraindications" and "Interaction with other drugs and other types of drug interactions").

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

In patients taking GnRH agonists, a decrease in glucose tolerance was observed. 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 Casodex ® in combination with GnRH agonists, it is necessary to monitor the concentration of glucose in the blood.

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

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

Form release / dosage:Tablets, film-coated, 50 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:

5 years.

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

Terms of leave from pharmacies:On prescription

Registration number:P N 013292/01

Date of registration:19.02.2010

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®)