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

Excipients: lactose monohydrate 135 mg / 397 mg, povidone-K30 4 mg / 10 mg, magnesium stearate 2 mg / 6 mg, sodium carboxymethyl starch 8 mg / 24 mg, silicon colloidal dioxide 1 mg / 3 mg;

film coating: film coating Instacoat 4 mg / 10 mg (hypromellose 1.6 mg / 4 mg, macrogol 0.8 mg / 2 g, talc 0.8 mg / 2 mg, titanium dioxide 0.8 mg / 2 mg.

Description:

For a dosage of 50 mg. Round, biconvex tablets, covered with a film coat of white color. There is a risk on one side. On the cross section, the nucleus is white or almost white in color.

For dosage 150 mg. Round, biconvex tablets, covered with a film coat of white color. On the cross section, the nucleus is white or almost white in color.

Pharmacotherapeutic group:Antitumor agent, antiandrogen

ATX: & nbsp

L.02.B.B.03 Bicalutamide

Pharmacodynamics:

Bicalutamide is a racemic mixture with non-steroidal antiandrogenic activity predominantly (R) -enantiomer, does not have a different endocrine activity. Bicalutamide binds to androgen receptors and, without activating the expression of genes, suppresses the stimulating effect of androgens. The result is regression of malignant neoplasms of the prostate gland. In some patients, discontinuing bicalutamide may lead to the development of a clinical "anti-androgen withdrawal syndrome".

Pharmacokinetics:

After oral administration bicalutamide 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 blood 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 in the blood 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.

On the pharmacokinetics (R) -enantiomer does not affect age, impaired renal function, mild or moderate liver function disorder. There is evidence that in patients with severe impairment of liver function, elimination is slowed down (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 by the kidneys and intestines in approximately equal proportions.

Indications:

- Common prostate cancer 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 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 bicalutamide and auxiliary components of the drug;

- simultaneous reception with terfenadine, astemizole and cisapride;

- bicalutamide should not be given to children and women.

Carefully:

If the 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 CYP3A4, with a deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Pregnancy and lactation:

The drug is contraindicated in women and should not be given to pregnant women or during breastfeeding.

Dosing and Administration:

Inside, regardless of food intake, drink a sufficient amount of liquid. Adults and elderly men:

With advanced prostate cancer in combination with an analogue of GnRH or surgical castration: inside by 50 mg once a day. Treatment should begin 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 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

In patients with impaired renal function, dose adjustment is not required.

Dysfunction of the liver

In patients with mild violations of liver function, dose adjustment is not required. If the liver function of moderate and severe severity, there may be an increased cumulation of bicalutamide. In severe hepatic insufficiency, despite the fact that T1/2 the active enantiomer of bicalutamide is increased by 76%, however, dose adjustment is not required.

Side effects:

Side effects arising from the application of bicalutamide - tablets coated with a film coating of 50 mg. - very frequently (≥1 / 10): anemia, gynecomastia (can be maintained even after cessation of therapy, especially in the case of taking the drug for a long time), breast pain, fatigue, rash. - commonly (≥1 / 100 - <1/10): "tides" heat *, anemia *, dizziness *, abdominal pain *, constipation *, nausea *, edema *, haematuria * Hepatotoxicity, transient increase in activity of "liver "enzymes, jaundice (described changes in liver function rarely estimated as lasting, often were transient in nature, completely disappeared or decreased during continued therapy or after drug withdrawal), loss of appetite, reduced libido, depression, drowsiness, dyspepsia, flatulence, alopecia, hirsutism or restoration of hair growth, dry skin, to zhny itching, erectile dysfunction, chest pain, weight gain, heart attack (reported fatal cases) ** ** heart failure, lengthening the interval QT. - rarely (≥1 / 10,000 - <1 / 1,000): hypersensitivity reactions, angioedema, urticaria, interstitial lung disease (reported cases of fatalities) ** photosensitivity reactions.- very rarely (<1 / 10,000): liver failure (reported fatal cases).

* 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 of bicalutamide-coated tablets 150 mg: - very often (≥1 / 10): gynecomastia (may persist even after discontinuation of therapy, especially when taking the drug for a long time), tenderness of the pancreas, skin rash, asthenia. - 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, increased transaminase activity, hepatotoxicity, jaundice, anemia, decreased appetite. - infrequent (≥1 / 1,000 - <1/100): hypersensitivity reactions, including angioedema and urticaria, interstitial lung disease (reported fatal cases) *.- rarely (≥1 / 10,000 - <1 / 1,000): photosensitivity reactions, hepatic failure (reported fatal cases) *. Transient increase in activity "hepatic" transaminases, cholestasis and jaundice were rarely evaluated as serious, transient in nature, completely disappeared or decreased with continued therapy or after drug withdrawal. Very rarely on the background of treatment with bicalutamide, hepatic insufficiency developed, but the causal relationship between the development of liver failure and drug treatment was not established reliably.

* According to the post-registration application of bicalutamide.

Overdose:

Cases of overdose in humans are not described. There is no specific antidote. Treatment is symptomatic. Dialysis is not effective, because bicalutamide strongly binds to plasma proteins and is not excreted by the kidneys in unchanged form. General supportive therapy and monitoring of the vital vital functions of the body are shown.

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 isoenzyme CYP3A4, to a lesser extent, affect the activity of isoenzymes CYP2C9, CYP2C19 and CYP2D6. The potential for bicalutamide to interact with other drugs has not been detected, however, when used for 28 days against the background of taking midazolam, the area under the concentration-time curve (AUC) Midazolam increases by 80%.

Inhibition of isoenzyme CYP3A4 under the action of bicalutamide can make a difference when using drugs with a narrow therapeutic index, which are metabolized in the liver. In this regard, the simultaneous use of bicalutamide with terfenadine, astemizole and cisapride is contraindicated.

Caution should be exercised in prescribing bicalutamide simultaneously with cyclosporine or blockers of "slow" calcium channels. 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 use or elimination of bicalutamide, it is recommended that the concentration of cyclosporin in the blood plasma and the clinical condition of the patient be carefully monitored.

When prescribing bicalutamide together with other drugs that can inhibit microsomal oxidation of drugs, for example, cimetidine and ketoconazole, caution should be exercised. Possible increase concentration of bicalutamide in the blood plasma with a subsequent increase in the incidence of adverse reactions. Strengthens the effect of indirect anticoagulants (coumarin derivatives), incl. warfarin (competition for communication with plasma proteins). Since with antiandrogen therapy, there is a risk of lengthening the interval QT, caution should be exercised with the simultaneous use of bicalutamide 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, neuroleptics, etc.

Special instructions:

Given the possibility of slowing the excretion of bicalutamide and its cumulation 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, bicalutamide 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 bicalutamide treatment.

In the appointment of bicalutamide to patients receiving indirect anticoagulants (coumarin derivatives), incl. warfarin, it is recommended to monitor prothrombin time on a regular basis.

Each tablet of the drug Bicalutamide 50 mg and 150 mg contains 135 and 397 mg of lactose monohydrate, respectively.

Taking into account the possibility of bicalutamide inhibition of the activity of cytochrome P450 (isoenzyme CYP3A4), caution should be exercised in the simultaneous administration of bicalutamide with drugs predominantly metabolized with the participation of the isoenzyme CYP3A4.

When used simultaneously with GnRH agonists, a decrease in glucose tolerance may occur, which may lead to the development of diabetes mellitus or a decrease in glucose tolerance in patients with diabetes mellitus. In this connection, in patients receiving bicalutamide in combination with GnRH agonists, it is necessary to monitor the concentration of glucose in the blood.

When co-administered with cyclosporine, after the use or discontinuation of bicalutamide is started, careful monitoring of the patient's condition and control of the concentration of cyclosporine in the blood plasma is recommended.

Each tablet of the drug Bicalutamide 50 mg and 150 mg contains lactose monohydrate 135 mg and 397 mg respectively, thus caution should be exercised for patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

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

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

Care should be taken when driving vehicles and machinery, because some side effects of the drug, such as asthenia, headache, dizziness, drowsiness and insomnia, can adversely affect the ability to perform work,requiring increased concentration of attention and speed of psychomotor reactions. If these side effects appear, you should refrain from performing these activities.

Form release / dosage:Tablets, film-coated, 50 mg, 150 mg.

Packaging:

For 10 tablets in an aluminum / PVC blister.

By 1,2, 3, 4, 5 or 10 blisters together with instructions for use in a pack of cardboard. By 7, 10, 14, 15, 28, 30, 100, 500 or 1000 tablets per package of polyethylene. The package is placed in a polymer can (PEVP) with a pull-on or screw-on lid with the control of the first opening. Free space is filled with cotton wool. On the bank stick a label from paper label or writing or from polymer materials, self-adhesive. 50, 100, 150, 200, 300, 500, or 1000 cans, together with an equal number of instructions for use, are placed in a group package - corrugated cardboard box (for hospitals).

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-004155

Date of registration:22.02.2017

Expiration Date:22.02.2022

The owner of the registration certificate:Pharmaceuticals Nord, JSCPharmaceuticals Nord, JSC Russia

Manufacturer: & nbsp

Biosyntez Laboratories Private Limited India

Representation: & nbspPharmasynthesis, JSCPharmasynthesis, JSC

Information update date: & nbsp21.03.2017

Illustrated instructions

Instructions

Bicalutamide (Bicalutamide)