Bicalutamide-Teva pills 150 mg, 28 pcs.

Composition

Active ingredients:

bicalutamide 150 mg.

Auxiliary substances:

microcrystalline cellulose,

povidone K-30,

croscarmellose sodium,

sodium lauryl sulfate,

lactose monohydrate,

colloidal silicon dioxide,

magnesium stearate.

Composition of the film shell:

opadray OY-GM-28900 white (hypromellose 2910/15 cP (E 464), polydextrose (E 1200), titanium dioxide, macrogol 4000).

Pharmacological action

Pharmacodynamics

Antitumor drug, an antiandrogenic nonsteroidal drug.

Bicalutamide is a racemic mixture with non-steroidal antiandrogenic activity mainly of the (R) – enantiomer, and has no other endocrine activity. Bicalutamide binds to androgen receptors and, without activating gene expression, suppresses the stimulating effect of androgens. The result is a regression of malignant neoplasms of the prostate gland.

In some patients, discontinuation of bicalutamide may lead to the development of a clinical “antiandrogen withdrawal syndrome”.

Pharmacokinetics

Suction and distribution

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. Food intake does not affect absorption.

With daily administration of bicalutamide, the concentration of the (R)-enantiomer in plasma increases approximately 10 times due to a long T_1/2, which makes it possible to take the drug 1 time/day. When bicalutamide is taken daily at a dose of 50 mg, the C_ss (R) – enantiomer in plasma is about 9 micrograms/ml. When taking 150 mg of bicalutamide daily, the C_ss (R) – enantiomer is approximately 22 micrograms / ml. At steady state, about 99% of all enantiomers circulating in the blood are the active (R)-enantiomer.

Binding to plasma proteins is high (96% for the racemic mixture,99.6% for the (R) – enantiomer).

Metabolism and elimination

It is intensively metabolized in the liver (by oxidation and formation of conjugates with glucuronic acid). Metabolites are excreted in the urine and bile in approximately equal proportions.

The (S) – enantiomer is eliminated from the body much faster than the (R) – enantiomer, T_1/2 of the latter-about 7 days.

Pharmacokinetics in special clinical cases

The pharmacokinetics of the (R)-enantiomer are not affected by age, renal impairment, or mild to moderate hepatic impairment. There is evidence that the elimination of the (R)-enantiomer from plasma slows down in patients with severe hepatic impairment.

Indications

• Common prostate cancer in combination with an analogue of GnRH (gonadotropin-releasing hormone) or surgical castration;
• locally common prostate cancer (T 3-T 4, any N, M 0; T 1-T 2, N+, M 0) as monotherapy or adjuvant therapy in combination with radical prostatectomy or radiotherapy,
• locally common nemetallicheskie prostate cancer in cases where surgical castration or other medical intervention inapplicable or inappropriate.

Use during pregnancy and lactation

Bicalutamide is contraindicated in women and should not be given to pregnant or nursing mothers.

Contraindications

• Concomitant use with terfenadine, astemizole and cisapride;
• lactose intolerance, lactase insufficiency or glucose / galactose malabsorption;
• hypersensitivity to bicalutamide and auxiliary components of the drug. Bicalutamide should not be given to children or women.

With caution: the drug should be prescribed if liver function is impaired.

Side effects

The pharmacological action of bicalutamide may cause the following side effects:

• very common ( > 10%): gynecomastia (may persist even after discontinuation of therapy, especially if the drug is taken for a long time), soreness of the mammary glands, “hot flashes” of blood to the face, decreased sexual desire, sexual dysfunctions.
• often (≥1%, but
• rarely (≥ 0.1%, but
• very rare (≥ 0.01%, but

When bicalutamide and GnRH analogues are co-administered, the following adverse events may also occur with a frequency of ≥ 1% (no causal relationship with the drug has been established, some of the reported side effects occurred in elderly patients):

From the cardiovascular system: heart failure, angina pectoris, conduction disorders, including prolongation of PR and QT intervals, rhythm disorders, non-specific ECG changes, increased blood pressure, myocardial infarction, syncope.

From the digestive system: stomach bleeding, anorexia, dry mouth, dyspepsia, constipation, flatulence, periodontal abscess, stomach/intestinal cancer.

Nervous system disorders: dizziness, headache, insomnia, anxiety, drowsiness, neuropathy.

From the respiratory system: shortness of breath, chest pain, cough, pharyngitis, bronchitis, pneumonia, rhinitis, bronchospasm, nosebleeds.

From the urinary system: nocturia, dysuria, urinary retention, edema, frequent urination, hydronephrosis, infections.

From the hematopoietic system: anemia.

Dermatological reactions: alopecia, skin rash, excessive sweating, hirsutism, dry skin, herpes infection, skin cancer.

Musculoskeletal disorders: myasthenia gravis, myalgia, seizures, arthritis, joint contractures, bone pain, leg cramps.

From the laboratory parameters: hyperglycemia, increased alkaline phosphatase activity, hypercreatininemia, hypercholesterolemia, hyperbilirubinemia.

Other: diabetes mellitus, polyuria, weight gain or loss, abdominal pain, chest pain, pelvic pain, sexual dysfunction, tumor development, chills, dehydration, gout, cataracts.

Interaction

There are no data on pharmacokinetic or pharmacodynamic interactions between bicalutamide and GnRH analogues.

In vitro studies have shown that the (R)-enantiomer of bicalutamide inhibits CYP3A4, affecting to a lesser extent the activity of CYP 2C9,2C19 and 2D6. Bicalutamide has not been shown to interact with other medicinal products, but when used for 28 days while taking midazolam, the AUC of midazolam increases by 80%.

Incompatible with terfenadine, astemizole, cisapride. Caution should be exercised when prescribing bicalutamide concomitantly with cyclosporine or calcium channel blockers. It may be necessary to reduce the dose of these drugs, especially if the effect is potentiated or side effects develop. After starting or discontinuing bicalutamide, careful monitoring of cyclosporine plasma concentrations and the patient’s clinical condition is recommended.

Concomitant use of bicalutamide and drugs that inhibit microsomal oxidation of drugs, such as cimetidine or ketoconazole, may lead to an increase in the concentration of bicalutamide in plasma and, possibly, to an increase in the frequency of side effects.

Increases the effect of coumarin-type anticoagulants, including warfarin (competition for protein binding).

How to take, course of administration and dosage

Adult males (including the elderly):

In advanced prostate cancer, in combination with a GnRH analog or surgical castration,50 mg is prescribed orally 1 time/day. Treatment with Bicalutamide-Teva should be started simultaneously with the start of taking the GnRH analog or surgical castration.

With locally advanced prostate cancer,150 mg is prescribed orally 1 time / day. Bicalutamide-Teva should be taken for a long time, at least for 2 years. If there are signs of disease progression, the drug should be discontinued.

If renal function is impaired, no dose adjustment is required.

No dose adjustment is required for mild hepatic impairment. Patients with moderate to severe hepatic impairment may experience increased accumulation 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 binds strongly to proteins and is not excreted unchanged in the urine. General maintenance therapy and monitoring of vital body functions are indicated.

Special instructions

Given the possibility of slowing the elimination of bicalutamide and its accumulation 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-Teva. In case of severe changes in liver function, bicalutamide should be discontinued.

Discontinuation of treatment with Bicalutamide-Teva should be considered in patients with progressive disease with elevated prostate-specific antigen (PSA) levels.

When prescribing Bicalutamide-Teva to patients receiving coumarin-type anticoagulants, it is recommended to regularly monitor prothrombin time.

Patients with lactose intolerance should be informed that each Bicalutamide-Teva 50 mg tablet contains 35 mg of lactose monohydrate, and each 150 mg tablet contains 105 mg of lactose monohydrate.

Given the possibility that bicalutamide may inhibit the activity of cytochrome P450 (CYP3A4) enzymes, caution should be exercised when prescribing Bicalutamide-Teva concomitantly with drugs primarily metabolized with the participation of CYP3A4.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

During the treatment period, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Film-coated tablets

Storage conditions

In a dark place, at a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Bicalutamide

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Cancer

Bar code and weight

Weight: 26 gr.