Composition, form of production and packaging
The tablets covered with a film shell of white or almost white color, round, biconcave, with engraving "L" on one side and "RG" on the other.
bicalutamide 50 mg
Excipients: silicon dioxide colloid, magnesium stearate, povidone K30, sodium carboxymethyl starch (type A), lactose monohydrate.
Sheath composition: opedrai II33G28707 white (triacetin, macrogol 3000, lactose monohydrate, titanium dioxide, hypromellose).
15 pcs. - blisters (2) - packs of cardboard.
15 pcs. - blisters (6) - packs of cardboard.
The tablets coated with a white or almost white film cover are round, biconvex, with an engraved "XL" on one side and "RG" on the other.
bicalutamide 150 mg
Excipients: silicon dioxide colloid - 1.5 mg, magnesium stearate - 1.875 mg, povidone - 12 mg, sodium carboxymethyl starch (type A) - 18 mg, lactose monohydrate - 191.625 mg.
Sheath composition: opedrai II.33G28523 white 7.5 mg (glyceryl triacetate 6%, macrogol 3000 8%, lactose monohydrate 21%, titanium dioxide 25%, hypromellose 40%).
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
Antiandrogenic nonsteroid drug. It is a racemic mixture, with anti-androgenic activity predominantly possessing the (R) -enantiomer. Does not have other kinds of endocrine activity.
It binds to androgen receptors and, without activating the expression of genes, suppresses the stimulating effect of androgens. The result is regression of malignant neoplasms of the prostate gland.
In some patients, discontinuing bicalutamide may lead to the development of a clinical "anti-androgen withdrawal syndrome".
After taking the drug inside, bicalutamide is quickly and completely absorbed from the digestive tract. Eating does not affect absorption.
The binding with plasma proteins is high (for a racemic mixture of 96%, for the (R) -enantiomer of 99.6%). Intensively metabolized in the liver by oxidation and the formation of conjugates with glucuronic acid.
With the daily administration of the drug Kalumid В®, the concentration of the (R) enantiomer in the plasma increases by about 10 times due to prolonged T 1/2 , which makes it possible to take the drug 1 time / day.
With the daily administration of the drug Kalumid В® in a dose of 50 mg C ss (R) -enantiomer in the plasma is about 9 mcg / ml, and when 150 mg of the preparation Kalumid В® - 22 mcg / ml. At an equilibrium state, about 99% of all enantiomers circulating in the blood form the active (R) -enantiomer.
Intensively metabolized in the liver (by oxidation and the formation of conjugates with glucuronic acid).
Metabolites are excreted by the kidneys and through the intestine in approximately equal proportions.
(S) -enantiomer is eliminated from the body much faster (R) -enantiomer, T 1/2 of the latter about 7 days.
Pharmacokinetics in special clinical cases
The pharmacokinetics of the (R) -enantiomer does not depend on age, renal dysfunction, and also on mild or moderate liver dysfunction.
There is evidence that in patients with moderate or severe impairment of liver function, the elimination of the (R) enantiomer from the plasma slows down and bicalutamide cumulation may occur.
- common prostate cancer in combination therapy with GnRH analogue (gonadotropin releasing hormone) or in combination with surgical castration (for tablets 50 mg);
- locally advanced prostate cancer (T3-T4, any N, M0, T1-T2, N +, M0) as monotherapy or adjuvant therapy in combination with radical prostatectomy or radiotherapy;
- locally advanced non-metastatic prostate cancer in cases where surgical castration or other drug-related interventions are inapplicable or unacceptable.
Adult men (including the elderly) with advanced prostate cancer in combination with an analogue of GnRH or surgical castration drug is prescribed in a dose of 50 mg 1 time / day. Treatment with Kalumid В® should be started at the same time as the beginning of the GnRH analogue or surgical castration.
With locally advanced prostate cancer , 150 mg once a day are prescribed. Kalumid В® should be taken for a long time, at least for 2 years. If signs of disease progression appear, the drug should be discontinued.
If the renal function is not corrected, dose adjustment is not required.
If the liver function is mild , no dose correction is required. In patients with moderate to severe hepatic impairment, increased cumulation of the drug may occur.
The pharmacological action of bicalutamide can cause the following side effects:
Very often (? 10%): gynecomastia (can persist even after cessation of therapy, especially in case of taking the drug for a long time), tenderness of the mammary glands, hot flushes.
Often (? 1% and <10%): diarrhea, nausea, transient increase in hepatic transaminase activity, cholestasis and jaundice (described changes in liver function have rarely been evaluated as serious, transient, completely disappeared or decreased with continued therapy or after drug withdrawal ), itching, asthenia; when using the drug at a daily dose of 150 mg - alopecia or hair regrowth, decreased sexual desire, sexual dysfunction, weight gain.
Rarely (? 0.1% and <1%): hypersensitivity reactions, including angioedema and urticaria, interstitial lung diseases; when using the drug in a daily dose of 150 mg - abdominal pain, depression, dyspepsia, hematuria.
Very rarely (? 0.01% and <0.1%): vomiting, dry skin (with the use of the drug in a daily dose of 150 mg, dry skin is often observed), liver failure (cause-and-effect relationship with bicalutamide is not established).
With the simultaneous use of bicalutamide and gonadotropin-releasing hormone analogues (GnRH), the following side effects can also occur with a frequency of> 1% (no cause-and-effect relationship with taking the drug has been established, some of the reported side effects have been observed in elderly patients).
From the cardiovascular system: heart failure.
On the part of the digestive system: anorexia, dry mouth, indigestion, constipation, flatulence.
From the nervous system: dizziness, headache, insomnia, increased drowsiness.
From the respiratory system: shortness of breath.
From the genitourinary system: sexual dysfunction, nocturia.
From the hematopoietic system: anemia.
From the skin and its appendages: alopecia, rash, excessive sweating, hirsutism.
Other: diabetes, hyperglycemia, increased or decreased body weight, abdominal pain, chest pain, pelvic pain, chills.
- simultaneous administration with terfenadine, astemizole, cisapride;
- Hypersensitivity to the components of the drug.
Kalumid В® is not prescribed for women and children.
Caution should be given to the drug for violation of liver function, lactase deficiency, lactose intolerance, malabsorption of glucose / galactose (in the drug form of the drug contains lactose).
PREGNANCY AND LACTATION
Bicalutamide is contraindicated in women and should not be given to pregnant and lactating mothers.
APPLICATION FOR FUNCTIONS OF THE LIVER
If the renal function is not corrected, dose adjustment is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Caution is prescribed for violations of liver function. With minor violations of liver function, dose adjustment is not required.
APPLICATION FOR CHILDREN
Calumid В® is not prescribed for children.
APPLICATION IN ELDERLY PATIENTS
The application is possible according to the dosing regimen.
Given the possibility of slowing the excretion of bicalutamide and its cumulation 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 Kalumid.
In the case of development of pronounced changes in liver function, Kalumida intake should be discontinued.
In patients with progression of the disease against a background of increased levels of prostate-specific antigen (PSA), consideration should be given to discontinuing Kalumid treatment.
When appointing Kalumida, patients receiving anticoagulants of the coumarin series are advised to regularly monitor prothrombin time.
Given the possibility of inhibition of the activity of cytochrome P450 (CYP3A4) by Kalumid, caution should be exercised when concomitant administration of Kalumid with preparations predominantly metabolized with CYP3A4.
Patients with lactose intolerance should be informed that 1 tablet of 50 mg contains 63.875 mg of lactose monohydrate, 1 tablet of 150 mg contains 191.625 mg of lactose monohydrate.
Impact on the ability to drive vehicles and manage mechanisms
Kalumid В® does not affect the ability of patients to drive vehicles or engage in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.
Cases of overdose in humans are not described. The specific antidote is not known. Treatment is symptomatic. Dialysis is not effective, since bicalutamide binds firmly to proteins and is not excreted in the urine unchanged. General supportive treatment and strict control of vital body functions are recommended.
There is no evidence of pharmacokinetic or pharmacodynamic interactions between bicalutamide and GnRH analogues.
In vitro studies have shown that the (R) -enantiomer of bicalutamide inhibits CYP3A4, to a lesser extent affecting the activity of CYP2C9, 2C19 and 2D6.
Potential ability of bicalutamide to interact with other drugs has not been revealed, however, when bicalutamide is used for 28 days with midazolam, the area under the midazolam AUC curve increases by 80%.
Incompatible with terfenadine, astemizole, cisapride.
Caution should be exercised in prescribing bicalutamide simultaneously with cyclosporine or calcium channel blockers. It may be necessary to reduce the dose of these drugs, especially in the case of potentiation or the development of side effects. After the beginning of the use or elimination of bicalutamide, it is recommended that the concentration of cyclosporin in the plasma be carefully monitored and the patient's clinical condition monitored.
The simultaneous use of bicalutamide and drugs depressing microsomal oxidation of drugs, for example, with cimetidine or ketoconazole may lead to an increase in bicalutamide concentration in the plasma and, possibly, an increase in the incidence of side effects.
Strengthens the effect of anticoagulants coumarin series, warfarin (competition for the connection with proteins).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of reach of children at a temperature of no higher than 30 В° C. Shelf life of tablets 50 mg - 5 years, tablets 150 mg - 2 years.