Bikalutamide-Sigardis - instructions for use, dose, side effects, contraindications

An antitumor agent, a nonsteroidal antiandrogenic drug is a competitive antagonist of endogenous androgens. The drug does not have other kinds of endocrine activity. Linking to androgen receptors on the surface of the cells of the target organs makes them inaccessible to androgens, thereby 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 to treat 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 reduces the risk of progression of the disease and the relative risk of metastasis in the bone during the observation period to 2 years.

At the same time, the effectiveness of bicalutamide in relation to survival rates is lower than that for 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:

Absorption:

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 (C_ss) (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.

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 per 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 approximately 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. (R) -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:

- Common prostate cancer;

- 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;

- locally advanced non-metastatic prostate cancer in cases where surgical castration or other medical interventions are not applicable or are unacceptable.

Contraindications:

Hypersensitivity to the components of the drug; childhood; female.

Carefully:Pin violation of liver function of moderate and severe severity; In patients with known risk factors for lengthening the interval QT or taking drugs that extend the interval QT; with the simultaneous use of "slow" calcium channels with cyclosporine or blockers, with drugs depressing microsomal oxidation of drugs (cimetidine and ketoconazole), with preparations, mainly metabolized with the participation of isoenzyme CYP3F4, with a deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Dosing and Administration:

With advanced prostate cancer in combination with an analogous GnRg (gonadotropin-releasing hormone) or surgical castration: inside by 50 mg once a day. Treatment with drug Bicalutamide -Sigardis must be started at the same time or 3 days before the start of the GnRH analogue or simultaneously with surgical castration.

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

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

If the liver function of moderate and severe severity, there may be an increased cumulation of biculutamide.

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:

Side effects arising from the use of bicalutamide - film-coated tablets 50 mg:

- very often (≥ 1/10): anemia, gynecomastia (may persist even after discontinuation of therapy, especially if the drug is taken for a long time), tenderness of the mammary glands, asthenia, rash;

- often (≥ 1/100 - <1/10): "hot flashes", anemia *, dizziness *, abdominal pain *, constipation *, nausea *, swelling *, hematuria *, hepatotoxicity. transient increase in the activity of "liver" transaminases, jaundice (described changes in liver function were rarely estimated as serious, often were transient in nature,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 fatal cases) **, heart failure **, lengthening of the interval QT;

- rarely (≥ 1/10000 - ≤1 / 1000): hypersensitivity reactions, angioedema, hives, interstitial lung diseases (reported fatal cases), photosensitivity reactions *;

* When taking the drug in combination with the analogues of gonadotropin-releasing hormone (GnRH), the side effect was observed very often.

** A side effect was observed when taking the drug.

Side effects arising from the use of bicalutamide - tablets coated with a film coat 150 mg:

- very often (≥ 1/10): gynecomastia (can be maintained even after cessation of therapy, especially in the case of taking the drug for a long time), breast tenderness, skin rash, fatigue:

- often (≥ 1/100 - <1/10): depression, anorexia, dizziness, drowsiness, hot flashes, itching, abdominal pain, constipation, dyspepsia, flatulence, alopecia or hair regrowth / hirsutism, decreased sexual desire, erectile dysfunction, chest pain, swelling, weight gain, increase transaminase activity, hepatotoxicity, jaundice, anemia, decreased appetite;

- infrequently (≥ 1/1000 - 1/100): hypersensitivity reactions, including angioedema and urticaria, interstitial lung diseases (reported fatal cases) *;

- rarely (≥ 1/10000 - 1/1000): photosensitivity reactions, 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.

Rarely on the background of treatment with bicalutamide, hepatic insufficiency developed, but the causal relationship between the development of hepatic insufficiency and treatment with the drug was not established reliably.

* According to the post-registration application of bicalutamide.

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, ketocoMr.azole).

Since with antiandrogen therapy, there is a risk of lengthening the interval QT, caution should be exercised when using bicalutamide simultaneously with drugs that cause lengthening of the interval QT or drugs capable of inducing ventricular tachycardia such as pirouettes, such as antiarrhythmic drugs of the class IA (eg, quinidine, disopyramide), Class III (for example, amiodarone, sotalol, dofetilide, ibutilide), methadone, moxifloxacin. antipsychotics.

Special instructions:

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

Study 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.

With antiandrogen therapy, there is a risk of lengthening the interval QT. Prior to the appointment of the drug should carefully evaluate the relationship between the benefits and risk of ventricular tachycardia tina pirouette in patients with known risk factors for lengthening the interval QT or taking drugs that extend the interval QT.

Each tablet of Bicalutamide Cygardis 50 mg and 150 mg contains 62.25 mg and 186.75 mg of lactose monohydrate, respectively, thus caution is necessary for patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

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:

Film-coated tablets, 50 mg and 150 mg.

Packaging:

Tablets 50 mg: 10 tablets in PVDC / PVC / aluminum blister. By 2, 3 or 6 blisters with instructions for use in a pack of cardboard.

Tablets of 150 mg: for 14 or 15 tablets in PVDC / PVC / aluminum blister. For 2 or 4 blisters with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-004007

Date of registration:07.12.2016

Expiration Date:07.12.2021

The owner of the registration certificate:SIGARDIS ENG, LLCSIGARDIS ENG, LLC Russia

Manufacturer: & nbsp

West Pharma Produces de Especialidades Farmaceuticas, S.A. Portugal

Representation: & nbspSigardis Rus, Open CompanySigardis Rus, Open Company

Information update date: & nbsp25.01.2017

Illustrated instructions

Instructions

Bicalutamide-Siguardis (Bicalutamid-Sigardis)