Bikalutamid Kanon

General characteristics. Structure:

Dosage of 50 mg
1 tablet, film coated contains:
active agent: бикалутамид 50 mg;
excipients: starch of corn 35 mg, croscarmellose sodium (primelloza) of 6,5 mg, lactoses monohydrate (sugar milk) 44,3 mg, povidone of 3,2 mg, sodium of the stearylfumarating 1 mg;
structure of a film cover: Опадрай II white 4 mg, including: polyvinyl alcohol of 1,6 mg, macrogoal (polyethyleneglycol) of 0,808 mg, talc of 0,592 mg, titanium dioxide of 1 mg.

Dosage of 150 mg
1 tablet, film coated contains:
active agent: бикалутамид 150 mg;
excipients: starch of corn 107 mg, croscarmellose sodium (primelloza) of 19,5 mg, lactoses monohydrate (sugar milk) 132,9 mg, povidone of 7,6 mg, sodium of the stearylfumarating 3 mg;
structure of a film cover: Опадрай II white 12 mg, including: polyvinyl alcohol of 4,8 mg, macrogoal (polyethyleneglycol) of 2,424 mg, talc of 1,776 mg, titanium dioxide of 3 mg.

Description:
Tablets, film coated white or almost white color, round, biconvex.

Pharmacological properties:

Pharmacodynamics. Antineoplastic means, nonsteroid anti-androgenic drug – the competitive antagonist of endogenous androgens. Contacting receptors on a surface of cells of target organs, does them unavailable to androgens, increasing at the same time concentration of hormones in plasma. Regression of new growths of a prostate is result of it.
Use of a bikalutamid in a dose of 150 mg/days sick with localized (T1-T2, N0 or NX, MO) or locally-spread (TZ-T4, any N, M0; any T, N+, M0) a prostate cancer the risk of progressing of a disease and relative risk of innidiation in a bone reduces.
At the same time efficiency of a bikalutamid concerning indicators of survival is lower that when performing surgical castration.
At some patients the termination of reception can lead to development of a syndrome of "cancellation" of anti-androgens (after cancellation at 10-15% of patients there occurs temporary stabilization of a disease).

Pharmacokinetics. After intake it is quickly and completely soaked up from the digestive tract (DT) (meal does not influence absorption). Communication with proteins of plasma - 96-99%. It is intensively metabolized in a liver (by oxidation and formation of conjugates with glucuronic acid) to inactive (S) - and active (R) - enantiomer. Time of achievement of the maximum concentration in a blood plasma (Tstakh) (R) - an enantiomer - 31.3 h.
(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 in a dose of 150 mg/days equilibrium concentration in a blood plasma (Css) (R) - an enantiomer of-22 mkg/ml. At Css about 99% of all enantiomer circulating in blood make active (R) - an enantiomer. At daily reception concentration (R) - an enantiomer in plasma increases approximately by 10 times owing to long T1/2. It is removed in the form of metabolites by kidneys and with bile in equal ratios. The pharmacokinetics (R) - an enantiomer does not depend on age, a condition of function of kidneys against the background of a moderate abnormal liver function; at patients with heavy abnormal liver functions elimination (R) - an enantiomer from plasma is slowed down.

Indications to use:

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

Route of administration and doses:

Adult men, including elderly:
At a widespread prostate cancer in a combination with an analog of GNRG or surgical castration: inside on 50 mg once a day.
At a locally-spread prostate cancer: inside 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:
At an easy abnormal liver function of dose adjustment it is not required. At patients with abnormal liver functions of average and heavy degree drug cumulation can be observed - dose adjustment is required.

Features of use:

Bikalutamid is intensively metabolized in a liver. Considering a possibility of delay of removal of a bikalutamid and cumulation of a bikalutamid at patients with the expressed abnormal liver function, it is reasonable to estimate function of a liver periodically.
The majority of changes of function of a liver meet within the first six months of treatment by drug.
Bikalutamid it is necessary to apply with care at patients with an average and heavy abnormal liver function.
Heavy disturbances of a liver when using drug arise seldom, was reported about cases with a fatal outcome. In case of development of the expressed changes of function of a liver and/or increase in functional trials more than twice administration of drug needs to be stopped.
At joint reception with cyclosporine, after the beginning of use or cancellation of a bikalutamid it is recommended to carry out careful control of concentration of cyclosporine in plasma and conditions of the patient.
At patients with progressing of a disease against the background of increase in concentration of prostatspetsifichesky antigen (EXPERT) it is necessary to consider a question of the treatment termination bikalutamidy.
Considering a possibility of inhibition drug of activity of P450 cytochrome (CYP 3A4 isoenzyme), it is necessary to show care at simultaneous use of a bikalutamid with the drugs which are preferential metabolized with participation of an isoenzyme of CYP 3A4. It is regularly recommended to control a prothrombin time at purpose of a bikalutamid to the patients receiving indirect anticoagulants of a coumarinic row.
At the patients accepting GNRG agonists decrease in portability of glucose was observed. This effect can lead to development of a diabetes mellitus or decrease in tolerance to glucose at patients with a diabetes mellitus. In this connection, at the patients accepting бикалутамид in a combination with GNRG agonists it is necessary to control concentration of glucose in blood.

Influence on ability to manage vehicles and other mechanisms:
At use of a bikalutamid drowsiness and dizziness in this connection it is necessary to be careful at control of motor transport or other moving mechanisms can be observed.

Side effects:

WHO classification of frequency of development of side effects:
very often-> 1/10 appointments (> 10%)
often          - from> 1/100    to <1/10 appointments (> 1% and <10%)
infrequently      - from> 1/1000  to <1/100 appointments (> 0.1% and <1%)
seldom          - from> 1/10000 to <1/1000 appointments (> 0.01% and <0.1%)
very seldom - <1/10000 appointments (<0.01%)
Classification of undesirable side reactions according to defeat of bodies and systems of bodies (the medical dictionary for normative and legal activity of Med-DRA).

Disturbances from immune system:
seldom - hypersensitivity reactions, including a Quincke's disease, a small tortoiseshell, skin rash.
Disturbances from endocrine system:
very often - a gynecomastia (can remain even 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, decrease or increase in body weight, a hyperglycemia, a diabetes mellitus.
Disturbances from a nervous system:
often - an asthenic syndrome, dizziness, sleeplessness or drowsiness, uneasiness, a loss of appetite, it is rare - a depression, "inflows" of blood to the person.
Disturbances from heart:
often - stenocardia, development or aggravation of heart failure, increase in arterial pressure.
Disturbances from respiratory system, bodies of a thorax and a mediastinum:
seldom - a stethalgia, cough, pharyngitis, bronchitis, pneumonia, intersticial pulmonary diseases (including with a fatal outcome), rhinitis.
Disturbances from digestive tract:
often - nausea; seldom - an abdominal pain, dyspepsia, a lock, diarrhea, vomiting, a meteorism, gastric bleeding, dryness of a mucous membrane of an oral cavity.
Disturbances from a liver and biliary tract:
seldom - tranzitorny increase in activity of "hepatic" transaminases, a cholestasia, jaundice; very seldom - a liver failure (including with a fatal outcome).
Disturbances from skin and hypodermic fabrics:
often - an alopecia, a hirsutism or a growth recovery of hair, a xeroderma.
Disturbances from skeletal and muscular and connecting fabric:
often - a myasthenia, a mialgiya, spasms, arthritis, contractures of joints.
Disturbances from kidneys and urinary tract:
infrequently - a dysuria, a polyuria, an ischuria, peripheral hypostases; seldom - a hamaturia.
The general frustration and disturbance in an injection site:
often - fever, a grippopodobny syndrome, a fever, the increased sweating, pain in pelvic area.
Laboratory and tool data:
often: anemia.

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, to a lesser extent influencing activity of isoenzymes of CYP 2C9, 2C19, 2D6. In clinical trials with use of phenazone as a marker of activity of P450 (CYP) cytochrome potential ability of drug to interaction with other drugs is not revealed, however at use of a bikalutamid within 28 days against the background of midazolam reception, the area under a curve "concentration - time" (AUC) of midazolam increased by 80%.
Contraindicated simultaneous use of a bikalutamid with such drugs, as терфенадин, астемизол and цизаприд. It is necessary to be careful at use of a bikalutamid along with cyclosporine, blockers of "slow" calcium channels; the medicines inhibiting microsomal enzymes of a liver, for example, with Cimetidinum or ketokonazoly (the dose decline of these drugs perhaps will be required). Simultaneous use can lead to increase in concentration of a bikalutamid in plasma and, perhaps, to increase in frequency of emergence of side effects.
Strengthens effect of indirect anticoagulants of a coumarinic row, including, warfarin (the competition for communication with proteins). It is regularly recommended to control a prothrombin time at purpose of a bikalutamid to the patients receiving indirect anticoagulants of a coumarinic row.

Contraindications:

Hypersensitivity to a bikalutamid or other components of drug;
Deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption;
Women;
Children's age;
Concomitant use with terfenadiny, astemizoly and tsizapridy.

With care:
At an abnormal liver function.

Use at pregnancy and during breastfeeding:
Bikalutamid Kanon is contraindicated to women and should not be appointed pregnant or in the period of a lactation.

Overdose:

Overdose cases at the person are not described. There is no specific antidote. Overdose treatment - symptomatic, monitoring of the vital functions of an organism is necessary. The hemodialysis is inefficient as it бикалутамид strongly contacts proteins of plasma and is not removed with urine in not changed look.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 50 mg, 150 mg.
For tablets dosage of 50 mg: on 7, 10 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 2, 4 blister strip packagings on 7 tablets or on 1, 3, 6 blister strip packagings on 10 tablets, or on 1, 2 blister strip packagings on 30 tablets together with the application instruction place in a pack from a cardboard.
For tablets dosage of 150 mg: on 7, 10 or 15 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 2, 4 blister strip packagings on 7 tablets or on 1, 3, 6 blister strip packagings on 10 tablets, or on 2, 4 blister strip packagings on 15 tablets together with the application instruction place in a pack from a cardboard.