Pharmacological properties of the drug Casodex
A nonsteroidal antiandrogen with no other hormonal activity. The drug is a racemic mixture in which only the (R)-enantiomer exhibits antiandrogenic activity. It binds to androgen receptors without activating gene expression, thereby suppressing the activity of androgens. The result is regression of the prostate tumor. Well absorbed from the digestive tract after oral administration. Food intake does not affect the bioavailability of bicalutamide. The (S)-enantiomer is excreted from the body much more quickly than the (R)-enantiomer; the half-life of the latter is approximately 1 week. When taking Casodex daily, the concentration of the (R)-enantiomer in the blood plasma increases approximately 10-fold due to the long half-life, which allows the drug to be taken once a day. When taking Casodex daily at a dose of 50 mg, the concentration of the (R)-enantiomer in the blood plasma is approximately 9 μg/ml, at a dose of 150 mg - about 22 μg/ml. Moreover, almost 99% of the drug in the systemic circulation is the active (R)-enantiomer. The pharmacokinetics of the (R)-enantiomer does not depend on factors such as age, the functional state of the kidneys and liver (with a slight or moderate impairment). In patients with severely impaired liver function, the elimination of the (R)-enantiomer is slowed down. Substantially binds to plasma proteins (racemate 96%, R-bicalutamide 99.6%). Intensively metabolized in the body through oxidation and the formation of glucuronide conjugates. Metabolites are excreted in urine and bile in approximately equal proportions.
Casodex tab p/pl/o 150 mg N28 (AstraZeneca)
Pharmacodynamics Antiandrogenic non-steroidal drug. It is a racemic mixture, and the (R)-enantiomer has predominantly antiandrogenic activity. The drug does not have other types of endocrine activity. Casodex® binds to androgen receptors and, without activating gene expression, suppresses the stimulating effect of androgens. As a result, regression of prostate tumors occurs. In some patients, discontinuation of Casodex may lead to the development of clinical antiandrogen withdrawal syndrome. When using Casodex at a daily dose of 150 mg daily for the treatment of patients with locally advanced (T3-T4, any N, M0 or any T, N+, M0) prostate cancer, as immediate hormonal therapy or as adjuvant therapy, significantly reduces the risk of disease progression and bone metastases. In locally advanced prostate cancer, there is a trend towards improved life expectancy without signs of disease progression in groups of patients receiving Casodex® 150 mg as immediate therapy or adjuvant therapy, compared with standard therapy (surgery, radiation therapy). An increase in life expectancy was shown among patients with locally advanced prostate cancer receiving Casodex® at a dose of 150 mg as immediate monotherapy and as adjuvant treatment in combination with radiation therapy. The use of Casodex at a dose of 150 mg compared with surgical castration in patients with locally advanced non-metastatic prostate cancer did not reveal a statistically significant difference in life expectancy and time to progression in statistically significant advantage of sexual function and physical condition. Pharmacokinetics Absorption After oral administration, it is quickly and completely absorbed from the gastrointestinal tract. Simultaneous food intake does not affect absorption. Distribution When taking Casodex daily at a dose of 150 mg, the Css (R) enantiomer in plasma is about 22 μg/ml. At steady state, about 99% of all enantiomers circulating in the blood are the active (R)-enantiomer. When taking Casodex daily, the concentration of the (R)-enantiomer in plasma increases approximately 10-fold due to a long T1/2, which allows taking Casodex 1 time per day .The binding to plasma proteins is high (for the racemic mixture 96%, for the (R)-enantiomer 99.6%). The average concentration of the (R)-enantiomer in the semen of men receiving Casodex 150 mg is 4.9 μg/ml. The amount of bicalutamide that can potentially be detected in women after sexual intercourse is low and is approximately 0.3 mcg/kg (a value of this indicator lower than that required for changes in fetal development in laboratory animals). Metabolism: Extensively metabolized in the liver by oxidation and the formation of conjugates with glucuronic acid. acid. Excretion Metabolites are excreted in urine and bile in approximately equal proportions. The (S)-enantiomer is excreted from the body much faster than the (R)-enantiomer, T1/2 of the latter is about 7 days. Pharmacokinetics in special clinical cases The pharmacokinetics of the (R)-enantiomer are not affected by age, impaired renal function, mild and moderate impaired liver function. There is evidence that in patients with severe liver dysfunction, the elimination of the (R)-enantiomer from plasma is slowed down. In patients with moderate and severe liver dysfunction, accumulation of bicalutamide in the body may be observed.
Indications for use of the drug Casodex
Indications for Casodex 50 mg . Advanced prostate cancer (late stages); used in combination with an analogue of luteinizing hormone releasing factor (LH-RH) or surgical castration. Indications for Casodex 150 mg . Locally progressive prostate cancer (T3–T4, any N, M0; T1–T2, N+, M0), as a stand-alone drug or as an adjuvant to radical prostatectomy or radiotherapy. Locally progressive, non-metastatic prostate cancer, in cases where surgical castration or other medical intervention is not considered appropriate or possible.
Use of the drug Casodex
Casodex 50 mg. Men, including the elderly: 1 tablet (50 mg) per day. Treatment with Casodex should be started simultaneously with the prescription of an LH-RH analogue or surgical castration. The duration of treatment is determined by the doctor. Casodex 150 mg. Adult men, including the elderly: 1 150 mg tablet orally once daily. Casodex 150 mg should be taken continuously for at least 2 years or until changes in the development of the disease appear. No dose adjustment is required in patients with renal failure and mild liver dysfunction. In order to avoid possible accumulation, Casodex should be prescribed to patients with moderate and severe liver dysfunction with caution.
Side effects of the drug Casodex
Casodex was well tolerated by most patients, and only in isolated cases did side effects require discontinuation of its use.
Frequency | Organs and organ systems | Side effects |
| Very common (≥10%) | Reproductive system and mammary glands | Breast tenderness 1 Gynecomastia 1 |
| General violations | Feelings of heat1 (hot flashes) | |
| Common (≥1% but ≤10%) | Gastrointestinal disorders | Diarrhea, nausea |
| Disorders of the hepatobiliary system | Increased transaminase activity, jaundice 2 | |
| General violations | Asthenia Itchy skin | |
| Rare (≥0.1% but ≤1%) | The immune system | Hypersensitivity reactions, including angioedema and urticaria |
| Respiratory, thoracic and mediastinal disorders | Interstitial lung diseases | |
| Very rare (≥0.01% but ≤0.1%) | Gastrointestinal disorders | Vomit |
| Skin and subcutaneous tissues | Dry skin | |
| Hepatobiliary system disorders | Liver failure 3 |
1 - The severity of these side effects can be reduced by concomitant castration. 2 - Changes in the liver are most often transient in nature and completely disappear or decrease with continued treatment or after its discontinuation. 3 - Liver failure occurred very rarely, a cause-and-effect relationship has not been established. It is recommended to periodically monitor liver function.
In addition, during clinical studies with the simultaneous use of Casodex and an LH-RH analogue, the following reactions were noted with a frequency of ≥1%, which were regarded as possible side effects: from the cardiovascular system - heart failure; from the gastrointestinal tract - anorexia, dry mouth, dyspepsia, constipation, flatulence; from the central nervous system - dizziness, insomnia, drowsiness, decreased libido; from the respiratory system - shortness of breath; from the genitourinary system - impotence, nocturia; from the blood system - anemia; on the part of the skin and its appendages - alopecia, rash, excessive sweating, hirsutism; from metabolic disorders - diabetes mellitus, hyperglycemia, edema, weight gain, weight loss; general disorders - pain in the abdomen, chest, pelvis, as well as headache, fever. However, a reliable cause-and-effect relationship between these side effects and the therapy has not been established. Some of these effects are general and often occur in elderly patients.
Casodex, 28 pcs., 150 mg, film-coated tablets
The pharmacological action of bicalutamide can cause the following side effects:
- very often (>10%) - gynecomastia (may persist even after cessation of therapy, especially if the drug is taken for a long time), tenderness of the mammary glands, flushing of the face, decreased libido, sexual dysfunction;
- often (>1%, but <10%) - diarrhea, nausea, transient increase in the activity of liver transaminases, cholestasis and jaundice (the described changes in liver function were rarely assessed as serious, were transient in nature, completely disappeared or decreased with continued therapy or after discontinuation drug), itching, asthenia; when using the drug in a daily dose of 150 mg - alopecia or hair regrowth, weight gain;
- rarely (>0.1%, but <1%) - hypersensitivity reactions, including angioedema and urticaria, interstitial pulmonary diseases; when using the drug in a daily dose of 150 mg - abdominal pain, depression, dyspepsia, hematuria;
- very rarely (>0.01%, but <0.1%) - vomiting, dry skin (when using the drug in a daily dose of 150 mg, dry skin is often observed), liver failure (a cause-and-effect relationship with taking bicalutamide has not been reliably established ).
With the simultaneous use of bicalutamide and GnRH analogues, the following side effects may also be observed with a frequency of >1% (a cause-and-effect relationship with the drug has not been established; some of the observed side effects occurred in elderly patients).
From the cardiovascular system:
heart failure, angina pectoris, conduction disturbances, including prolongation of the PR and QT intervals, rhythm disturbances, nonspecific changes on the ECG, increased blood pressure, myocardial infarction, fainting.
From the digestive system:
stomach bleeding, anorexia, dry mouth, dyspepsia, constipation, flatulence, periodontal abscess, stomach/intestinal cancer.
From the nervous system:
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.
From the skin and its appendages:
alopecia, skin rash, excessive sweating, hirsutism, dry skin,
herpes zoster
, skin cancer.
From the musculoskeletal system:
myasthenia gravis, myalgia, cramps, arthritis, joint contractures, bone pain, leg cramps.
From the laboratory parameters:
hyperglycemia, increased alkaline phosphatase, hypercreatininemia, hypercholesterolemia, hyperbilirubinemia.
Other:
diabetes mellitus, polyuria, increase or decrease in body weight, pain in the abdomen, chest, pelvic area, sexual dysfunction, development of the tumor process, chills, dehydration, gout, cataracts.
Special instructions for the use of Casodex
Since Casodex is extensively metabolized by the liver, its elimination may be delayed in patients with severe hepatic impairment and this, in turn, may lead to accumulation of Casodex. Therefore, Casodex should be prescribed to such patients with caution. Liver function testing should be performed periodically during Casodex therapy. Most of these changes can be expected in the first 6 months of treatment with Casodex. If severe liver disorders occur, treatment with Casodex should be discontinued. Casodex inhibits cytochrome P450 (CYP 3A4), so caution should be exercised when prescribing Casodex with drugs metabolized by CYP 3A4. Patients with lactose intolerance should take into account that each Casodex 150 mg tablet contains 183 mg of lactose monohydrate. Use during pregnancy and lactation. The use of Casodex is contraindicated in women during pregnancy and breastfeeding. Children . Casodex is contraindicated in children. The ability to influence the reaction rate when driving a vehicle or working with other mechanisms . Casodex is unlikely to affect patients' ability to drive vehicles or operate machinery. However, it should be noted that drowsiness may sometimes occur. Patients taking this drug should use caution.
Drug interactions Casodex
There is no data on the interaction of Casodex and LH-RH analogues. In vitro studies have demonstrated that R-bicalutamide inhibits CYP 3A4 and, to a lesser extent, CYP 2C9, 2C19 and 2D6. Although clinical studies with antipyrine, a marker of P450 activity, did not confirm the possibility of interaction with Casodex, use of the drug for 28 days while taking midazolam led to an increase in the AUC value of midazolam by 80%. Therefore, the use of Casodex with terfenadine, astemizole and cisapride is contraindicated. Caution must be exercised when prescribing Casodex with cyclosporine or calcium channel blockers. The dose of these drugs may need to be reduced. Patients taking cyclosporine should be under medical supervision, especially when starting treatment with Casodex and when discontinuing it. Caution must be exercised when prescribing Casodex with drugs that inhibit drug metabolism (cimetidine, ketoconazole). Theoretically, the administration of such a combination may lead to an increase in the concentration of Casodex in the blood and the incidence of side effects. In vitro studies have shown that Casodex can displace the coumarin anticoagulant warfarin from the sites of its binding to plasma proteins. Therefore, when prescribing Casodex in patients receiving coumarin anticoagulants, it is recommended to regularly monitor prothrombin time.
Casodex, 50 mg, film-coated tablets, 28 pcs.
The pharmacological action of bicalutamide can cause the following side effects:
- very often (>10%) - gynecomastia (may persist even after cessation of therapy, especially if the drug is taken for a long time), tenderness of the mammary glands, flushing of the face, decreased libido, sexual dysfunction;
- often (>1%, but <10%) - diarrhea, nausea, transient increase in the activity of liver transaminases, cholestasis and jaundice (the described changes in liver function were rarely assessed as serious, were transient in nature, completely disappeared or decreased with continued therapy or after discontinuation drug), itching, asthenia; when using the drug in a daily dose of 150 mg - alopecia or hair regrowth, weight gain;
- rarely (>0.1%, but <1%) - hypersensitivity reactions, including angioedema and urticaria, interstitial pulmonary diseases; when using the drug in a daily dose of 150 mg - abdominal pain, depression, dyspepsia, hematuria;
- very rarely (>0.01%, but <0.1%) - vomiting, dry skin (when using the drug in a daily dose of 150 mg, dry skin is often observed), liver failure (a cause-and-effect relationship with taking bicalutamide has not been reliably established ).
With the simultaneous use of bicalutamide and GnRH analogues, the following side effects may also be observed with a frequency of >1% (a cause-and-effect relationship with the drug has not been established; some of the observed side effects occurred in elderly patients).
From the cardiovascular system:
heart failure, angina pectoris, conduction disturbances, including prolongation of the PR and QT intervals, rhythm disturbances, nonspecific changes on the ECG, increased blood pressure, myocardial infarction, fainting.
From the digestive system:
stomach bleeding, anorexia, dry mouth, dyspepsia, constipation, flatulence, periodontal abscess, stomach/intestinal cancer.
From the nervous system:
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.
From the skin and its appendages:
alopecia, skin rash, excessive sweating, hirsutism, dry skin,
herpes zoster
, skin cancer.
From the musculoskeletal system:
myasthenia gravis, myalgia, cramps, arthritis, joint contractures, bone pain, leg cramps.
From the laboratory parameters:
hyperglycemia, increased alkaline phosphatase, hypercreatininemia, hypercholesterolemia, hyperbilirubinemia.
Other:
diabetes mellitus, polyuria, increase or decrease in body weight, pain in the abdomen, chest, pelvic area, sexual dysfunction, development of the tumor process, chills, dehydration, gout, cataracts.
