Bikalutamid-Teva

General characteristics. Structure:

Active agent: бикалутамид 50,0 mg and 150,0 mg;
auxiliary substances: cellulose microcrystallic, povidone (PVP K-30), croscarmellose sodium, sodium lauryl sulfate, lactoses monohydrate, silicon dioxide colloid, magnesium stearate; cover of Opadray of OY-GM-28900 white: gipromelloza of 2910 15 Wednesday (E464), polydextrosum (E1200), titanium dioxide, macrogoal 4000;
Description:
Tablets of 50 mg: white or almost white round tablets, film coated with an engraving "93" on one party and "220" on another.
Tablets of 150 mg: white or almost white round tablets, film coated with an engraving of "BCL" on one party and equal on another

Pharmacological properties:

Pharmacodynamics. Bikalutamid represents racemic mix with nonsteroid anti-androgenic activity preferential (Рч) - an enantiomer, has no other endocrine activity. Bikalutamid contacts androgenic receptors and, without activating an expression of genes, suppresses the stimulating influence of androgens. Regression of malignant new growths of a prostate is result of it. At some patients the termination of reception of a bikalutamid can lead to development of a clinical "withdrawal of anti-androgens".

Pharmacokinetics. After intake it is quickly and completely soaked up from digestive tract. Meal does not influence absorption.
(H) - the enantiomer is brought out of an organism much quicker (Ру) - an enantiomer, an elimination half-life of the last - about 7 days.
At daily reception of a bikalutamid concentration (R.) in plasma increases approximately by 10 times owing to a long elimination half-life that does possible administration of drug once a day.
At daily reception of a bikalutamid in a dose of 50 mg equilibrium concentration (R) - an enantiomer in plasma makes about 9 mkg/ml. At reception of 150 mg of a bikalutamid daily equilibrium concentration (K) - an enantiomer makes about 22 mkg/ml. At an equilibrium state about 99% of all enantiomer circulating in blood make active (Rch.)-enantiomer.
The pharmacokinetics (K) - an enantiomer is not influenced by age, a renal failure, an easy and moderate abnormal liver function. There are data that at patients with heavy abnormal liver functions elimination (Ya) - an enantiomer from plasma is slowed down.
Communication with proteins of plasma high (for racemic mix of 96%, for (11) - an enantiomer of 99,6%). It is intensively metabolized in a liver (by oxidation and formation of conjugates with glucuronic acid). Metabolites are removed with urine and bile approximately in equal ratios.

Indications to use:

- A widespread prostate cancer in a combination with GNRG analog (a gonadotrophin-rileasing hormone) or surgical castration.
- Locally-spread prostate cancer (TZ-T4, any N, MO; T1-T2, N+, MO) as monotherapy or adjuvant therapy in combination with a radical prostatectomy or radiotheraphy.
- A locally-spread not metastatic prostate cancer in cases when surgical castration or other medical interventions are inapplicable 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. Treatment by Bikalutamid-Tev's drug needs to be begun along with the beginning of reception of an analog of GNRG or surgical castration.
At a locally-spread prostate cancer: inside on 150 mg once a day. Bikalutamid-Tev should be accepted it is long, at least within 2 years. At emergence of signs of progressing of a disease administration of drug should be stopped.
Renal failures: dose adjustment is not required.
The abnormal liver function, at an easy abnormal liver function dose adjustment is not required. At patients with average and heavy abnormal liver functions the increased Bikalutamida-Tev's cumulation can be observed.

Features of use:

Considering a possibility of delay of removal of a bikalutamid and its cumulation at patients with an 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 Bikalutamid-Tev's drug.
In case of development of the expressed changes of function of a liver reception of a bikalutamid needs to be stopped.
At patients with progressing of a disease against the background of increase in level of prostatspetsifichesky antigen (DOG) it is necessary to consider a question of the treatment termination by Bikalutamid-Tev's drug.

At Bikalutamida-Tev's appointment the patients receiving anticoagulants of a coumarinic row are recommended to control a prothrombin time regularly. Patients with a lactose intolerance need to be informed that each tablet of Bikalutamida-Tev of 50 mg contains 35 mg of lactose of monohydrate, the tablet of 150 mg contains 105 mg of lactose of monohydrate.

Considering a possibility of inhibition bikalutamidy activities of P450 cytochrome (CYP ZA4), it is necessary to show care at co-administration of drug of Bikalutamid-Tev with the drugs which are preferential metabolized with CYP ZA4 participation.
Bikalutamid is contraindicated to women and should not be appointed to pregnant and nursing mothers.
During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Pharmacological action of a bikalutamid can cause the following side effects:
- very often (> 10%): a gynecomastia (can remain even after the therapy termination, especially in case of administration of drug for a long time), morbidity of chest glands, "inflows" of blood to the person, decrease in sexual desire, sexual dysfunctions;
- often (> 1%, but <10%): diarrhea, nausea, tranzitorny increase in activity of "hepatic" transaminases, a cholestasia and jaundice (the described changes of function of a liver seldom were estimated as serious, had tranzitorny character, completely disappeared or decreased at continuation of therapy or after drug withdrawal), an itch, an adynamy; at use of drug in a daily dose of 150 mg - an alopecia or a growth recovery of hair, an increase in weight.
- seldom (> 0.1%, but <1%): hypersensitivity reactions, including a Quincke's disease and a small tortoiseshell, intersticial pulmonary diseases; at use of drug in a daily dose of 150 mg - an abdominal pain, a depression, dyspepsia, a hamaturia.
- very seldom (> 0.01%, but <0.1%): vomiting, a xeroderma (at use of drug in a daily dose of 150 mg the xeroderma is observed often), a liver failure (relationship of cause and effect is authentically not established with reception of a bikalutamid).
At simultaneous use of a bikalutamid and analogs of GNRG the by-effects provided below with a frequency> in 1% can be also observed (relationship of cause and effect is not established with administration of drug, some of noted side effects occurred at elderly patients):

From cardiovascular system: heart failure, stenocardia, conductivity disturbances, including lengthening of intervals of PR and QT, disturbance of a rhythm, nonspecific changes on an ECG, increase in the ABP, a myocardial infarction, a faint; From the alimentary system: gastric bleeding, anorexia, dryness in a mouth, dyspepsia, a lock, a meteorism, periodontal abscess, stomach/intestines cancer; From a nervous system: dizziness, headache, sleeplessness, uneasiness, drowsiness, neuropathy;
From respiratory system: asthma, stethalgia, cough, pharyngitis, bronchitis, pneumonia, rhinitis, bronchospasm, nasal bleeding;
From an urinary system: a nocturia, a dysuria, an ischuria, hypostases, the speeded-up urination, a hydronephrosis, infections; From the hemopoietic system: anemia;
From skin and its appendages: an alopecia, skin rash, the increased perspiration, a hirsutism, a xeroderma, herpes zoster, a carcinoma cutaneum;
From a musculoskeletal system: a myasthenia, a mialgiya, spasms, arthritis, contractures of joints, ostealgias, spasms in legs;
  From  laboratory  indicators:  hyperglycemia,  increase  in an alkaline phosphatase, giperkreatininemiya, hypercholesterolemia, hyperbilirubinemia; Other: diabetes mellitus, polyuria, increase or decrease in body weight, abdominal pain, breasts, pelvic area, sexual dysfunctions, development of tumoral process, fever, dehydration, gout, cataract.

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 (To) - the enantiomer of a bikalutamid inhibits CYP ZA4, to a lesser extent influencing activity of CYP 2C9, 2C19 and 2D6. Potential ability of a bikalutamid to interaction with other medicines is not revealed, however at its use within 28 days against the background of midazolam reception, the area under a curve "concentration time" of midazolam increases by 80%.
It is incompatible with terfenadiny, astemizoly, tsizapridy.
It is necessary to be careful at purpose of a bikalutamid along with cyclosporine or blockers of calcium channels. Perhaps, the dose decline of these drugs, especially, in case of potentiation of effect or development of by-effects will be required. After the beginning of use or cancellation of a bikalutamid recommend to carry out careful monitoring of concentration of cyclosporine in plasma and a clinical condition of the patient.
Simultaneous use of a bikalutamid and drugs, for example, Cimetidinum or a ketokonazol inhibiting a microsomal oxidation of medicines 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 anticoagulants of a coumarinic row, including warfarin (the competition for communication with proteins).

Contraindications:

- Hypersensitivity to a bikalutamid and auxiliary components of drug;
- A concomitant use with terfenadiny, astemizoly and tsizapridy;
- Bikalutamid should not be appointed to children and women;
- Lactose intolerance, lactose intolerance or malabsorption of glucose galactose.

With care: abnormal liver function.

Overdose:

Overdose cases at the person are not described. The specific antidote does not exist. Symptomatic treatment. Carrying out dialysis is not effective as бикалутамид strongly contacts proteins and is not removed with urine in not changed look. The general maintenance therapy and monitoring of the vital functions of an organism is shown.

Storage conditions:

List B. At a temperature not above 25 °C, in the place protected from light. To store in the place, unavailable to children. Period of validity: 3 years. Not to use drug after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated on 50 mg and 150 mg.
On 10 tablets in the blister from the PVC/PVDH/ave of a foil.
On 3 blisters together with the application instruction in a cardboard pack.
On 7 tablets in the blister from the PVC/PVDH/ave of a foil.
4 blisters together with the application instruction in a cardboard pack.