Бикана®

General characteristics. Structure:

Active ingredient: 50 mg or 150 mg of a bikatulomid.

Excipients: magnesium алюмометасиликат, carboxymethylstarch of sodium, magnesium stearate, лудипресс in terms of components: lactoses monohydrate, povidone, кросповидон.

Cover: Опадрай the II yellow 85F32771 (polyvinyl alcohol – 35,0 – 49,00%, talc of 9,80 - 25,00%, a macrogoal 3350 – 7,35 – 35,20%, titanium dioxide and ferrous oxide yellow – 15,15 – 30,00%), Opadray the II yellow 85F32733 (polyvinyl alcohol – 35,0 – 49,00%, talc – 9,80 – 25,00%, a macrogoal 3350 – 7,35 – 35,20%, titanium dioxide and ferrous oxide yellow – 15,15 – 30,00%).

Pharmacological properties:

Pharmacodynamics. Bikalutamid – antineoplastic means, represents racemic mix with nonsteroid anti-androgenic activity preferential (R) - an enantiomer, has no other endocrine activity. Bikalutamid contacts androgenic receptors on a surface of cells of target organs, suppresses stimulating influence of androgens, without activating an expression of genes. Regression of malignant new growths of a prostate results. At some patients the termination of reception of a bikalutamid can lead to development of a clinical syndrome of "cancellation" of anti-androgens.

Pharmacokinetics. Absorption: after intake бикалутамид it is quickly and completely soaked up from digestive tract. Meal does not influence bioavailability of drug. Time of achievement of the maximum concentration (TCmax) (R) - an enantiomer – 31,3 hours.

Distribution: communication with proteins of plasma high (for racemic mix – 96%, for (R) - an enantiomer of 99%).

Metabolism: it is intensively metabolized in a liver (by oxidation and formation of conjugates with glucuronic acid) to inactive (S) - and active (R) - enantiomer.

Removal: бикалутамид it is removed in the form of metabolites by kidneys and with bile in equal ratios. (S) - the enantiomer is brought out of an organism much quicker (R) - an enantiomer, an elimination half-life (T1/2) of the last – about 7 days. At daily reception of a bikalutamid concentration (R) - an enantiomer in plasma increases approximately by 10 times owing to long T1/2 that does possible administration of drug of 1 times a day. At daily reception of a bikalutamid in a dose of 50 mg equilibrium concentration (Css) (R) - an enantiomer in plasma makes about 9 mkg/ml.

At reception of 150 mg of a bikalutamid daily equilibrium concentration (R) - an enantiomer makes about 22 mkg/ml. At an equilibrium state about 99% of all enantiomer circulating in blood make active (R) - an enantiomer. The pharmacokinetics (R) - an enantiomer does not depend on age, a condition of function of kidneys, abnormal liver functions of easy or average degree. There are data that at patients with heavy degree of a liver failure removal (R) - an enantiomer from plasma is slowed down.

Indications to use:

Prostate cancer:

• treatment of a widespread prostate cancer in a combination with an analog a hormone gonadotrophin-rileasing (GNRG analog) or surgical castration;
• monotherapy or adjuvant therapy in combination with a radical prostatectomy or radiotheraphy of a locally-spread prostate cancer (T3-T4, any N, M0; T1-T2, N+, M0);
• treatment of a locally-spread, not metastatic prostate cancer in cases when surgical castration or other medical interventions are unacceptable or are not applicable.

Route of administration and doses:

Inside, regardless of meal, washing down with enough liquid. Drug is appointed to adult men (including advanced age).

At a widespread prostate cancer – inside on 50 mg once a day, in combination with a simultaneous initiation of treatment an analog of GNRG or surgical castration.

At a locally-spread not metastatic prostate cancer – on 150 mg once a day.

Bikalutamid it is necessary to accept for a long time, at least within 2 years. At emergence of signs of progressing of a disease administration of drug should be stopped.

Renal failure: dose adjustment is not required.

Abnormal liver function: dose adjustment is not required to patients with easy abnormal liver functions. At patients with average or heavy abnormal liver functions the increased cumulation of a bikalutamid in this connection drug should be used with care is possible.

Features of use:

Use at pregnancy and during breastfeeding. Drug is contraindicated to women and should not be appointed pregnant or during breastfeeding.

Bikalutamid is actively metabolized in a liver. Considering a possibility of delay of removal of a bikalutamid and its cumulation at patients with an abnormal liver function, it is necessary to estimate periodically function of a liver (the majority of changes of function of a liver meet within the first 6 months of treatment). In case of development of severe damages of a liver it is necessary to stop reception of a bikalutamid.

Considering a possibility of inhibition bikalutamidy CYP 3A4 isoenzyme, it is necessary to show care at simultaneous use with the drugs which are preferential metabolized with participation of an isoenzyme of CYP 3A4.

At joint reception with cyclosporine, after the beginning of use or cancellation of a bikalutamid it is recommended to carry out careful control of a condition of the patient and control of concentration of cyclosporine in plasma.

At purpose of a bikalutamid the patients receiving anticoagulants of a coumarinic row are recommended to control a prothrombin time regularly.

At simultaneous use with agonists of GNRG decrease in tolerance to glucose is possible that can be manifestation of a diabetes mellitus or decrease in level of glycemic control at already existing diabetes mellitus. Therefore it is necessary to control periodically concentration of glucose in blood serum.

At patients with a lactose intolerance development of adverse side reactions, such as a meteorism (abdominal distention), abdominal pains, diarrhea is possible, vomiting is more rare.

Patients with a lactose intolerance should be informed that each tablet Бикана® 50 of mg contains 124,6 mg of lactose of monohydrate, in the mg tablet Бикана® 150 – 373,8 mg of lactose of monohydrate.

At patients with progressing of a disease against the background of increase in concentration of prostatspetsifichesky antigen (DOG) it is necessary to consider a question of the treatment termination bikalutamidy.

Influence on ability to manage vehicles, mechanisms. It is necessary to be careful at control of vehicles and mechanisms since some side effects of drug, such as an adynamy, a headache, dizziness and sleep disorders, can negatively influence ability to performance of the work demanding the increased concentration of attention and speed of psychomotor reactions. At emergence of these side effects it is necessary to refrain from performance of the specified types of activity.

Side effects:

Bikalutamid is well had by most of patients, and only in rare instances it should be cancelled because of development of side effects. The side effects registered more often than single observations are listed below on bodies and systems with the indication of frequency of their emergence. Determination of frequency: very often (≥ 10%), it is frequent (≥ 1% and <10%), infrequently (≥ 0,1% and <1%), is rare (≥ 0,01% and <0,1%), is very rare (<0,01%).

Disturbances from bodies of a hemopoiesis: very often – анемия*.

Disturbances from endocrine system: very often – a gynecomastia (can remain after the therapy termination, especially in case of administration of drug for a long time), morbidity of chest glands; often - decrease in sexual desire, erectile dysfunction.

Disturbances from a nervous system: very often – dizziness *; drowsiness.

Disturbances from mentality: often – at use of drug in a daily dose of 150 mg – a depression.

Disturbances from heart: often - heart failure, a myocardial infarction.

The risk of emergence of complications from heart arises at use of a bikalutamid along with GNRG analogs.

Disturbances from vascular system: very often – "inflows" of heat to лицу*.

Disturbances from digestive tract: very often – nausea *, diarrhea, an abdominal pain *, a lock *, a loss of appetite; often - dyspepsia, a meteorism.

Disturbances from gepato-billiarny system: often - a hepatotoxic, tranzitorny increase in activity of "hepatic" transaminases, jaundice, a cholestasia (the described changes of function of a liver completely disappear or decrease at continuation of therapy or after drug withdrawal); seldom – a liver failure (it was reported about cases with a fatal outcome).

Disturbances from a metabolism and food: often – increase in body weight.

Disturbances from skin and hypodermic fabrics: often – skin rash, a skin itch; at use of drug in a daily dose of 150 mg – an alopecia, a growth recovery of hair, a hirsutism, a xeroderma.

Disturbances from respiratory system, bodies of a thorax and a mediastinum: often – a stethalgia; infrequently – intersticial pulmonary diseases (it was reported about cases with a fatal outcome).

Disturbances from kidneys and urinary tract: very often – гематурия*.

Disturbances from immune system: infrequently – hypersensitivity reactions, including a Quincke's disease and a small tortoiseshell.

General disturbances: very often – an adynamy, peripheral отеки*.
* At administration of drug of Bikana® in a dose of 50 mg in a combination with GNRG analogs the side effect was observed very often.

Interaction with other medicines:

There are no data on pharmacokinetic or pharmakodinamichesky interactions between bikalutamidy and GNRG analogs.

In the researches in vitro it is shown that (R) - the enantiomer of a bikalutamid inhibits CYP 3A4 isoenzyme, to a lesser extent influences activity of isoenzymes of CYP 2C9, CYP 2C19 and CYP 2D6. When using a bikalutamid within 28 days against the background of midazolam reception, the area under a kinetic curve "concentration time" (AUC) of midazolam increases by 80%.

CYP 3A4 isoenzyme inhibition under the influence of a bikalutamid can matter at use of medicines with a narrow therapeutic index which are metabolized in a liver. In this regard, simultaneous use of a bikalutamid with terfenadiny, astemizoly and tsizapridy is contraindicated.

It is necessary to be careful at purpose of a bikalutamid along with cyclosporine or blockers of "slow" calcium channels. In case of strengthening of effect or development of by-effects, the dose decline of these drugs will be required.

After the beginning or cancellation of therapy bikalutamidy it is recommended to carry out monitoring of a clinical condition of the patient and concentration of cyclosporine in a blood plasma.

To apply at the same time бикалутамид with the drugs oppressing a microsomal oxidation of medicines such as Cimetidinum and кетоконазол, follows with care since increase in concentration of a bikalutamid in a blood plasma is possible that can theoretically lead to increase in frequency of side effects.

Bikalutamid strengthens effect of anticoagulants of indirect action of a coumarinic number, for example, of warfarin (the competition for communication with proteins).

Contraindications:

Hypersensitivity to a bikalutamid or any other component of drug. Concomitant use of a terfenadin, astemizol and tsizaprid. Bikalutamid is contraindicated to children and women.

With care: a lactose intolerance, deficit of lactase and glyukozo-galaktozny malabsorption (since drug contains lactose); abnormal liver function; simultaneous use with cyclosporine or blockers of "slow" calcium channels; simultaneous use with the drugs oppressing a microsomal oxidation of medicines (Cimetidinum or кетоконазол).

Overdose:

About overdose cases at the person it was not reported.

Treatment: the specific antidote does not exist, symptomatic therapy. Carrying out dialysis is inefficient as бикалутамид strongly contacts proteins of plasma and is not removed by kidneys in not changed look. The general maintenance therapy and control of the vital functions of an organism is shown.

Storage conditions:

Period of validity - 3 years. Not to apply after the period of validity specified on packaging. In the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 50 mg, 150 mg. On 7 tablets in a blister strip packaging from a film of the polymeric and printing aluminum foil varnished. On the 4th blister strip packagings together with the application instruction place in a cardboard pack. On 10 tablets in a blister strip packaging from a film of the polymeric and printing aluminum foil varnished. On the 3rd blister strip packagings together with the application instruction place in a cardboard pack. On 14 tablets in a blister strip packaging from a film of the polymeric and printing aluminum foil varnished. On the 2nd blister strip packagings together with the application instruction place in a cardboard pack. On 28 or 30 tablets in bottles polymeric, corked by plastic covers. On a bottle paste the self-adhesive label. On 1 bottle together with the application instruction place in a cardboard pack.