Bicalutamide

Pharmacological properties

Arecloc is a non-steroidal anti-androgenic drug without other endocrine activity. bicalutamide binds to androgen receptors without activating gene expression and thus inhibits androgen stimuli. the result of this suppression is regression of prostate tumors. withdrawal of bicalutamide treatment may lead in some patients to antiandrogen withdrawal syndrome.

Bicalutamide has a low degree of affinity for sex hormone binding globulin (SHBG), but this does not have clinical significance.

The drug contains a racemic mixture with antiandrogenic activity, mainly due to the (R) -enantiomer.

Pharmacokinetics Bicalutamide is well absorbed after oral administration. There is no evidence of any clinically significant effect of food intake on the bioavailability of the drug.

The (S) -enantiomer is rapidly excreted from the body, compared to the (R) -enantiomer in which T_½ from blood plasma is about 1 week.

With prolonged use C_max The (R) -enantiomer of bicalutamide in blood plasma rises by about 10 times compared with indicators after taking a single dose of bicalutamide 50 mg.

With a daily intake of 50 mg of bicalutamide, the equilibrium concentration of the (R) -enantiomer is ≈9 μg / ml, and due to prolonged T_½ the equilibrium state is reached after approximately 1 month of treatment.

The pharmacokinetics of the (R) -enantiomer does not depend on the patients age, mild or moderate renal failure. Data were obtained that in patients with severe hepatic impairment, the (R) -enantiomer is more slowly excreted from blood plasma.

Bicalutamide (a racemic mixture of 96%, (R) -bicalutamide 99.6%) has a high degree of protein binding and is extensively metabolized in the liver by oxidation and the formation of glucuronide conjugates. Its metabolites are excreted by the kidneys and through the gallbladder in approximately equal proportions.

Indications

Prostate cancer (late stages) in combination with therapy with analogues of the releasing factor LH or surgical castration.

Application

Adult male patients, including the elderly: 1 tablet 1 time per day. treatment with bicalutamide should be started at least 3 days before the start of therapy with analogues of releasing factor LH or simultaneously with surgical castration.

In renal failure: individual dose adjustment is not required.

In case of liver failure: individual dose adjustment is not required for patients with moderate liver failure. The accumulation of bicalutamide is possible in patients with moderate or severe liver failure.

Children. The drug is contraindicated in children.

Contraindications

Bicalutamide is contraindicated in women and children. bicalutamide should not be prescribed to patients who have previously noted hypersensitivity reactions to bicalutamide or any of the components of the drug.

Concomitant use with terfenadine, astemizole or cisapride is contraindicated.

Side effects

Adverse reactions are classified by frequency: very often (≥1 / 10), often (≥1 / 100, 1/10), infrequently (≥1 / 1000, 1/100), rarely (≥1 / 10,000, 1/1000 ), very rarely (1/10 000), with an unknown frequency (based on the available data, it is impossible to establish the frequency of occurrence).

On the part of the blood and lymphatic system: very often - anemia.

From the immune system: infrequently - hypersensitivity, angioedema, urticaria.

From the side of metabolism and nutrition: often - a decrease in appetite.

From the side of the psyche: often - decreased libido, depression.

From the nervous system: very often - dizziness; often drowsiness.

On the part of the heart: often - myocardial infarction (reported fatal outcome)¹, heart failure¹.

From the vessels: very often - tides.

From the respiratory system, chest and mediastinal organs: infrequently - interstitial pulmonary disease (fatal outcome reported).

From the digestive system: very often - abdominal pain, constipation, nausea; often - dyspepsia, flatulence.

From the hepatobiliary system: often - hepatotoxicity, jaundice, increased transaminase activity²; rarely - liver failure³ (death reported).

On the part of the skin and subcutaneous tissue: often - alopecia, hirsutism / restoration of hair growth, dry skin, itching, rash.

From the kidneys and urinary system: very often - hematuria.

On the part of the reproductive system and mammary glands: very often - gynecomastia and soreness of mammary vaginas⁴; often - erectile dysfunction.

General disorders and reactions at the injection site: very often - asthenia, edema; often chest pain.

Examination: often - an increase in body weight.

¹The risk was increased while LH releasing factor was used with agonists; however, no increased risk was observed with Areclock monotherapy in patients with prostate cancer.

²Changes in the liver are rarely severe and often go away or become less pronounced during treatment or after its discontinuation.

³Patients have occasionally reported liver failure, but a causal relationship with the drug has not been precisely established. The advisability of periodically monitoring liver function should be considered.

⁴May decrease with concomitant castration.

special instructions

Treatment should begin under the direct supervision of a physician.

Bicalutamide is metabolized in the liver. Clinical data suggest that elimination may be slowed down in patients with severe liver damage, which may lead to the accumulation of bicalutamide. Therefore, the drug must be used with caution in patients with moderate to severe hepatic impairment.

When using bicalutamide, isolated cases of severe liver disease were noted, and fatal cases were also reported. Treatment should be discontinued if the changes are severe.

It is necessary to periodically monitor liver function to detect possible changes in the liver. Most changes are noted during the first 6 months of using the drug.

In men taking LH releasing factor agonists, a decrease in glucose tolerance is detected, which can be manifested by diabetes mellitus or loss of glycemic control in people with already diagnosed diabetes. In this regard, attention should be paid to controlling the level of glucose in the blood of patients taking the drug simultaneously with LH releasing factor agonists.

The drug inhibits the activity of cytochrome P450 (CYP 3A4), so caution should be exercised while using it with drugs that are metabolized primarily by CYP 3A4.

Patients with rare congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption cannot be prescribed with bicalutamide.

Use during pregnancy or lactation. The use is contraindicated.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Does not affect. However, it should be borne in mind that occasionally drowsiness may occur. Patients taking this medication should be careful.

Interactions

There is no evidence of pharmacodynamic or pharmacokinetic interactions between bicalutamide and analogues of releasing factor lh.

In vitro studies have shown that the (R) -enantiomer of bicalutamide is an inhibitor of CYP 3A4. To a lesser extent affects the activity of CYP 2C9, 2C19 and 2D6.

Despite the fact that in clinical trials using antipyrine as a marker of the activity of cytochrome P450 (CYP), bicalutamide has no potential ability to interact with other drugs, while bicalutamide and midazolam are used for 28 days, the AUC of midazolam increased by 80%.

In the case of drugs with a narrow therapeutic index, metabolized in the liver (such as terfenadine, astemizole, cisapride), the inhibition of CYP 3A4 caused by bicalutamide can be significant. Therefore, bicalutamide is contraindicated in conjunction with these drugs.

Bicalutamide should also be used with caution with compounds such as cyclosporine and calcium channel blockers. It may be necessary to reduce the dose of these drugs, especially if there are signs of an increase in the effect of the drug or the occurrence of side effects as a result of its use. When using cyclosporine, it is recommended to carefully monitor its concentration in the blood plasma and the clinical condition of the patient after the start or termination of treatment with bicalutamide.

With caution, bicalutamide should be prescribed when using drugs that can inhibit the oxidation of the product (such as cimetidine, ketocanosol). Theoretically, this can lead to an increase in the concentration of bicalutamide in blood plasma, which may lead to an increase in side effects of the drugs.

In vitro studies have shown that bicalutamide can replace warfarin at the site of its binding to proteins. Thus, in the case when treatment with bicalutamide begins in patients using coumarin anticoagulants, it is recommended to control prothrombin time.

Overdose

Cases of overdose were not observed. there is no specific antidote. symptomatic treatment.

Dialysis is ineffective, since bicalutamide has a high ability to bind to proteins and is not detected in urine unchanged. The usual supportive treatment is prescribed with monitoring of the vital functions of the body.

Storage conditions

It does not require special storage conditions.