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

Excipients: hypromellose-3Rs 50 mg, sodium lauryl sulfate 10 mg, microcrystalline cellulose 211 mg, crospovidone 35 mg, lactose monohydrate 40 mg, magnesium stearate 4 mg;

composition of the shell: opada white OY-58900 (hypromellose-5cP 62.5%, titanium dioxide 31.25%, macrogol 6.25%) 12 mg.

Description:

White, round, biconvex tablets, covered with a film sheath, embossed with "R"on one side and" 573 "on the other side.

Pharmacotherapeutic group:Antitumor agent - antiandrogen

ATX: & nbsp

L.02.B.B.03 Bicalutamide

Pharmacodynamics:

An antitumor agent, a non-steroidal antiandrogenic drug, is a competitive antagonist endogenous androgens.The drug does not have other kinds of endocrine activity. Linking to androgen receptors on the surface of the cells of target organs, makes them inaccessible to androgens, while increasing the concentration of hormones in the plasma. It does not activate gene expression, suppresses the stimulating effect of androgens. As a result, regression of prostate tumors occurs.

With daily application of bicalutamide in a daily dose of 150 mg, for the treatment of patients with localized (criteria T1-T2, N0 or NX, M0) or locally advanced (criteria T3-T4, any N, M0; T1-T2, N+, M0) prostate cancer, the risk of progression of the disease is reduced by 42% and the relative risk of metastasis in the bone by 33%, during the observation period to 2 years. At the same time, the effectiveness of bicalutamide, in terms of survival rates, is lower than that of surgical castration.

In some patients, discontinuation may lead to the development of a "withdrawal syndrome" of antiandrogens (after the abolition of 10-15% of patients, the temporary stabilization of the disease occurs).

Pharmacokinetics:

Suction

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

Distribution

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

With daily intake of bicalutamide, the concentration (R) -enantiomer in plasma increases approximately 10-fold due to a long half-life (T_1/2), which allows you to take bicalutamide 1 time / day.

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

Average concentration (R) -enantiomer in the semen of men who received bicalutamide 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.

Metabolism

Intensively metabolized in the liver by oxidation and the formation of conjugates with glucuronic acid.

Excretion

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

Pharmacokinetics in special clinical cases

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.

In patients with moderate and severe violations of liver function, cumulation of bicalutamide in the body can be observed.

Indications:

- RAscogenous prostate cancer (bicalutamide in a dose of 50 mg in combination with an analogue of GnRH (gonadotropin-releasing hormone) or surgical castration);

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

- locally advanced nonmetastatic prostate cancer (bicalutamide in a dose of 150 mg) in cases where surgical castration or other medical interventions are not applicable or are unacceptable.

Contraindications:

- Hypersensitivity to the components of the drug;

- simultaneous reception of terfenadine, astemizole and cisapride;

- childhood;

- female.

Carefully:

- Impaired liver function;

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

Dosing and Administration:

With advanced prostate cancer in combination with an analogue of GnRH or surgical castration: inside by 50 mg once a day. Treatment with Bikaprost® should be started simultaneously with the onset of GnRH analogue or surgical castration.

With locally advanced prostate cancer: inside by 150 mg once a day.

Bicaprost should be taken continuously for at least 2 years. If signs of disease progression appear, the drug should be discontinued.

In special clinical cases

Patients with renal dysfunction do not need dose adjustment.

Patients with mild dysfunction of the liver correction of the dose is not required.

Side effects:

Bicalutamide is well tolerated by most patients and it is only rarely that it has to be canceled because of the side effects it causes.

From the side of the cardiovascular system: angina pectoris, development or aggravation of heart failure, increased blood pressure.

From the respiratory system: pain in the chest, cough, pharyngitis, bronchitis, pneumonia, rhinitis.

From the digestive system: rarely - abdominal pain, flatulence, indigestion, gastric bleeding, dry mouth, transient increase in the activity of "liver" transaminases, cholestasis, jaundice; very rarely - a violation of the liver.

From the nervous system: dizziness, insomnia or drowsiness, anxiety; rarely - depression.

From the side of the musculoskeletal system: myasthenia gravis, myalgia, convulsions, arthritis, joint contractures.

From the endocrine system: often (> 10%) - gynecomastia (may persist after cessation of therapy, especially if the drug is taken for a long time), breast tenderness, hyperglycemia, diabetes, polyuria.

From the urinary system: dysuria, urinary retention, edema; rarely - hematuria.

Other: often - asthenia, alopecia, body weight decrease or increase, decreased libido, fever, chills, increased sweating, anemia, pelvic pain, dry skin, hirsutism, allergic reactions, "tides" of blood to the face.

Overdose:

Treatment: symptomatic, there is no specific antidote.Dialysis is ineffective, because bicalutamide strongly binds to proteins and is not excreted in the urine unchanged. The general supportive therapy and control over the vital functions of the body are shown.

Interaction:

Enhances the effects of anticoagulants of indirect action.

Increases the area under the pharmacokinetic curve (AUC) of midazolam by 80%.

Incompatible with terfenadine, astemizole, cisapride.

Increases the risk of adverse effects with concomitant administration with cyclosporine, slow calcium channel blockers, drugs depressing microsomal oxidation (including cimetidine, ketoconazole).

Special instructions:

When co-administered with cyclosporine after starting the use or the elimination of bicalutamide, careful monitoring of the plasma cyclosporin concentration and the patient's condition is recommended.

Research in vitro showed that bicalutamide can displace warfarin from binding sites with protein (regular prothrombin time monitoring).

Elimination of bicalutamide from the body can be slowed down in patients with severe impairment of liver function, which can lead to its cumulation.It is advisable to periodically evaluate liver function (most liver function changes occur during the first 6 months of treatment). Stop treatment if there are clinical symptoms and / or increase functional tests by more than 2 times.

In case of severe liver disease, bicalutamide should be discontinued.

In patients with progression of the disease against the background of an increase in the level of prostate-specific antigen, consideration should be given to discontinuing treatment.

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 dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 50 mg.

Packaging:

For 7 tablets in PVDC / PVC / aluminum blister. For 4 blisters with instructions for use in a pack of cardboard.

For 10 tablets in PVDC / PVC / aluminum blister. For 3 or 5 blisters with instructions for use 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:LP-001563

Date of registration:05.03.2012

Date of cancellation:2017-03-05

The owner of the registration certificate:Dr. Reddy's Laboratories Ltd.Dr. Reddy's Laboratories Ltd. India

Manufacturer: & nbsp

DR. REDDY`S LABORATORIES, LTD. India

Representation: & nbspDR REDDY'S LABORATORIS LTD. DR REDDY'S LABORATORIS LTD. India

Information update date: & nbsp22.11.2015

Illustrated instructions

Instructions

Bikaprost® (Bicaprost®)