Bicalutamide - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 58.45 mg (50 mg dosage) and 175.35 mg (150 mg dosage), povidone 3.50 mg (50 mg dosage) and 10.50 mg (150 mg dosage), sodium carboxymethyl starch 12.11 mg ( dosage of 50 mg) and 36.33 mg (150 mg dosage), magnesium stearate 0.94 mg (50 mg dosage) and 2.82 mg (150 mg dosage);

shell: opada white Y-1-7000 (hypromellose, titanium dioxide, macrogol) 3.0 mg (dosage of 50 mg) and 8.0 mg (dosage of 150 mg).

Description:

Round, biconvex tablets, covered with a film coat of white color. On the fracture tablets from white to almost white.

Pharmacotherapeutic group:Antitumor agent - antiandrogen

ATX: & nbsp

L.02.B.B.03 Bicalutamide

Pharmacodynamics:

Bicalutamide is a selective non-steroidal anti-androgenic, not possessing other kinds of endocrine activity. It is a racemic mixture with non-steroidal antiandrogenic activity predominantly (R) -enantiomer.

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

In some patients, discontinuing bicalutamide may lead to the development of a syndrome of "cancellation" of antiandrogens.

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 daily administration of bicalutamide at a dose of 50 mg, the equilibrium concentration of the (R) enantiomer in plasma 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.

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

Intensively and stereospecifically metabolized in the liver (by oxidation and the formation of conjugates with glucuronic acid). Metabolites are inactive, excreted by the kidneys and intestines in approximately equal proportions.

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 blood plasma.

Indications:

- Common prostate cancer in combination with an analogue of gonadotropin-releasing hormone (GnRH) or surgical castration;

- Locally spread prostate cancer (T3-T4, any N, M0, T1-T2, N +, M0) as monotherapy or adjuvant therapy in combination with radical prostatectomy or radiotherapy;

- Locally disseminated nonmetastatic prostate cancer in cases where surgical castration or other medical interventions are not applicable or are unacceptable.

Contraindications:

- Hypersensitivity to any component of the drug;

- simultaneous administration with terfenadine, astemizole, cisapride;

- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption (the preparation contains lactose);

- childhood.

It should not be given to female patients.

Carefully:

Violation of the function of the liver.

Dosing and Administration:

Inside.

Adult men (including the elderly)

With advanced prostate cancer in combination with an analogue of GnRH or surgical castration: 50 mg once a day. Treatment with bicalutamide should begin at the same time as the beginning of the GnRH analogue or surgical castration.

With locally advanced prostate cancer: 150 mg once daily. Bicalutamide 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: correction of the dose is not required.

Dysfunction of the liver: with a mild violation of liver function, dose adjustment is not required. In patients with moderate to severe hepatic impairment, an increased cumulation of bicalutamide may be observed.

Side effects:

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

- Often (>10%): gynecomastia (may persist even after cessation of therapy, especially if the drug is taken for a long time), soreness of the breast glands, "tides" of blood to the face;

- often (≥1% and <10%): diarrhea, nausea, transient, increased activity of "liver" transaminases, cholestasis and jaundice (described changes in liver function were rarely evaluated as serious, transient, completely disappeared or decreased with continued therapy or after drug withdrawal), itching, asthenia; when using the drug at a daily dose of 150 mg - alopecia or hair regrowth, decreased sexual desire, sexual dysfunction, weight gain.

- rarely (≥0,1% - <1%): hypersensitivity reactions, including angioedema and urticaria, interstitial lung diseases; angina pectoris,prolongation of the QT interval, heart rhythm disturbances; when using the drug in a daily dose of 150 mg - abdominal pain, depression, dyspepsia, hematuria.

- rarely (≥0,01% - <0,1%): vomiting, dry skin (with the use of the drug in a daily dose of 150 mg, dry skin is often observed), liver failure (cause-and-effect relationship with bicalutamide is not reliably established), thrombocytopenia.

With the simultaneous use of bicalutamide and GnRH analogues, the following adverse events with a frequency of ≥1% can also be observed (a causal relationship with the drug administration has not been established, some of the noted side effects have been observed in elderly patients):

From the cardiovascular system: heart failure.

From the digestive system: anorexia, dry mouth, indigestion, dysphagia, constipation, flatulence.

From the nervous system: dizziness, headache, insomnia, increased drowsiness.

From the respiratory system: dyspnea.

From the urinary system: nocturia, urinary tract infection, dysuria, urinary retention, frequent urination, polyuria, hydronephrosis.

From the hematopoietic system: anemia, and leukopenia.

From the skin and its appendages: alopecia, rash, excessive sweating, hirsutism.

From the laboratory indicators: hyperglycemia, increased activity of "liver" transaminases.

Other: abdominal pain, chest pain, pelvic pain, back pain, decreased or increased body weight, swelling, diabetes, fever.

Overdose:

Cases of overdose in humans are not described.

There is no specific antidote.

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

Interaction:

There is no evidence of pharmacokinetic or pharmacodynamic interactions between bicalutamide and GnRH analogues.

In studies in vitro shown, that (R) -enantiomer of bicalutamide inhibits CYP 3A4, to a lesser extent affecting the activity of CYP 2C9, 2C19, and 2D6. The potential for bicalutamide to interact with other drugs has not been revealed, however, when bicalutamide is used for 28 days with midazolam, the area under the concentration-time curve (AUC) of midazolam increases by 80%.

Incompatible with terfenadine, astemizole, cisapride.

Caution should be exercised in prescribing bicalutamide simultaneously with cyclosporine or calcium channel blockers. It may be necessary to reduce the dose of these drugs, especially in the case of potentiation or the development of side effects. After the beginning of the use or elimination of bicalutamide, it is recommended that the concentration of cyclosporin in the plasma be carefully monitored and the patient's clinical condition monitored.

Simultaneous application of bicalutamide and drugs that inhibit microsomal oxidation of drugs, such as ketoconazole or cimetidine may lead to an increase in plasma concentrations of bicalutamide, and possibly an increase in the incidence of adverse effects.

Strengthens the effect of anticoagulants coumarinovogo number, incl. warfarin (competition for communication with proteins).

Special instructions:

Given the possibility of slowing the excretion 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 bicalutamide.

In case of pronounced changes in liver function, the drug should be stopped.

In patients with progression of the disease against a background of increased levels of prostate-specific antigen (PSA), consideration should be given to discontinuing bicalutamide treatment.

When bicalutamide is prescribed, patients receiving anticoagulants of the coumarin series are advised to regularly monitor prothrombin time.

Taking into account the possibility of bicalutamide inhibition of cytochrome P450 (CYP 3A4), caution should be exercised while simultaneously prescribing bicalutamide with drugs predominantly metabolized with CYP 3A4.

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

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:The film-coated tablets are 50 mg and 150 mg.

Packaging:

For 14 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil.

2 contour squares, together with instructions for use, are placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:PL-000398

Date of registration:28.02.2011 / 04.07.2016

The owner of the registration certificate:Heterose Labs LimitedHeterose Labs Limited India

Manufacturer: & nbsp

HETERO LABS, Limited India

MAKIZ-PHARMA, LLC Russia

Representation: & nbspHeterose Labs LimitedHeterose Labs LimitedIndia

Information update date: & nbsp21.11.2015

Illustrated instructions

Instructions

Bicalutamide (Bicalutamide)