Instructions for use Bicalutamide-Teva film-coated tablets 50 mg No. 28
Composition
active ingredient: bicalutamide;
1 film-coated tablet contains 50 mg of bicalutamide;
Excipients: microcrystalline cellulose, povidone, croscarmellose sodium, sodium lauryl sulfate, lactose monohydrate, colloidal anhydrous silica, magnesium stearate, hypromellose, polydextrose, titanium dioxide (E 171), polyethylene glycol.
Dosage form
Film-coated tablets.
Main physicochemical properties: white or almost white, round, biconvex, film-coated tablets with embossing "93" on one side and "220" on the other; without cracks or chips.
Pharmacotherapeutic group
Antiandrogenic agents. ATX code L02B B03.
Pharmacological properties
Pharmacodynamics
Bicalutamide is a nonsteroidal antiandrogen agent devoid of other endocrine activity. It binds to androgen receptors without activating gene expression, thereby blocking androgen stimulation. This leads to regression of prostate tumors. In some patients, discontinuation of bicalutamide therapy may cause a withdrawal syndrome.
It is a racemic compound; only the (R)-enantiomer exhibits antiandrogenic activity.
Pharmacokinetics
Bicalutamide is well absorbed when taken orally. Food does not have any clinically significant effect on bioavailability.
Compared to the (R)-enantiomer, the (S)-enantiomer is rapidly eliminated from the body, with a half-life of about 1 week.
With daily administration of bicalutamide at a dose of 50 mg, the concentration of the (R)-enantiomer in the blood plasma increases 10-fold as a result of the long half-life.
With daily administration of bicalutamide at a dose of 50 mg, plasma concentrations of the (R)-enantiomer at the saturation stage are approximately 22 mg/ml. The predominantly active (R)-enantiomer accounts for 99% of the total circulating enantiomers at the saturation stage.
The pharmacokinetics of the (R)-enantiomer are not affected by age or mild to moderate renal or hepatic impairment. In severe hepatic impairment, the (R)-enantiomer is eliminated from the blood plasma more slowly.
Bicalutamide is highly protein bound (racemic: 96%, (R)-enantiomer: >99%) and extensively metabolized (by oxidation and glucuronidation); metabolites are excreted renally and biliarily in approximately equal proportions.
Indication
Treatment of metastatic prostate carcinoma in combination with a luteinizing hormone-releasing factor (LHRH) analogue or surgical castration.
Contraindication
- Hypersensitivity to bicalutamide or other components of the drug;
- concomitant treatment with terfenadine, astemizole or cisapride;
- contraindicated for use by women.
Interaction with other medicinal products and other types of interactions
Concomitant use of bicalutamide with terfenadine, astemizole, cisapride and cyclosporines is contraindicated. Caution should be exercised when prescribing cyclosporine and calcium channel blockers simultaneously. It may be necessary to reduce the dose of these drugs, especially if there are signs of increased drug exposure or side effects as a result of its use. When using cyclosporine, it is recommended to carefully monitor its plasma concentration and the patient's clinical condition after starting or stopping treatment with bicalutamide. Caution should also be exercised when concomitantly using substances that may inhibit the oxidation of bicalutamide, i.e. drugs containing ketoconazole or cimetidine. This may lead to an increase in bicalutamide plasma levels and the occurrence of adverse reactions. Bicalutamide is able to release the coumarin anticoagulant warfarin from its association with proteins. It is necessary to carefully monitor prothrombin time when prescribing bicalutamide to patients who are being treated with coumarin.
There is no evidence of a pharmacodynamic or pharmacokinetic interaction between bicalutamide and LH agonists.
Bicalutamide is an inhibitor of CYP 3A4 and exhibits a lesser inhibitory effect on the activity of CYP 2C9, 2C19 and 2D6.
Caution should be exercised when administering drugs that may prolong the QT interval or induce torsades de pointes, as antiandrogen therapy may also prolong the QT interval. These drugs include: class IA (e.g. quinidine, disopyramide) and class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmics, methadone, moxifloxacin, antipsychotics.
Application features
Treatment should be initiated under the close supervision of a specialist.
It is recommended to monitor liver function (at least once a month). Most changes in liver function are observed within the first 6 months of treatment with bicalutamide.
Rare cases of severe liver disorders and liver failure, sometimes fatal, have been reported with the use of bicalutamide.
If severe liver disorders occur while using Bicalutamide-Teva, treatment with the drug should be discontinued.
Bicalutamide is an inhibitor of cytochrome P450 (CYP 3A4), therefore caution should be exercised when using this drug together with drugs that are metabolized by CYP 3A4.
Impaired glucose tolerance has been observed in male patients treated with LH agonists, manifested by the development of diabetes mellitus or loss of glycemic control in those with pre-existing diabetes. Therefore, blood glucose levels should be closely monitored in patients receiving bicalutamide in combination with LH agonists.
Antiandrogen therapy may prolong the QT interval.
In patients with risk factors or a history of QT prolongation and in patients concomitantly taking medicinal products that may prolong the QT interval, the benefit/risk ratio should be assessed before starting treatment, also taking into account the possibility of torsades de pointes.
Since the drug contains lactose monohydrate, patients with rare hereditary problems of lactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Use during pregnancy or breastfeeding
The drug should only be used for the treatment of men.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug is not expected to affect the reaction rate when driving or using other mechanisms. However, patients who develop drowsiness should be especially careful and refrain from driving or using other mechanisms.
Method of administration and doses
Adult men, including the elderly: 1 tablet once a day, at the same time (morning or evening).
Treatment should be initiated within 1 week before the use of RFLG analogues or simultaneously with surgical castration.
Renal impairment: No dose adjustment is required.
Hepatic impairment. No dose adjustment is required for mild hepatic impairment. Increased accumulation of bicalutamide is possible in moderate and severe hepatic impairment.
Children
The drug is contraindicated in children.
Overdose
There are no data on overdose in humans. There is no specific antidote, treatment is symptomatic. Hemodialysis is ineffective. Supportive therapy is indicated, including monitoring of vital body functions.
Adverse reactions
From the circulatory and lymphatic systems: anemia.
Immune system disorders: hypersensitivity, angioedema, urticaria.
Cardiovascular system: hot flashes, myocardial infarction (fatal outcomes have been reported), heart failure, QT prolongation.
On the part of the digestive tract: abdominal pain, nausea, constipation, dyspepsia, flatulence.
Hepatobiliary system: hepatotoxicity, jaundice, increased transaminases, hepatic failure (fatal outcomes have been reported).
From the nervous system: dizziness, drowsiness.
Mental disorders: decreased libido, depression.
Respiratory system: interstitial lung disease (fatal outcomes have been reported).
Skin and subcutaneous tissue disorders: alopecia, hirsutism/hair regrowth, rash, dry skin, itching, photosensitivity reactions.
Renal and urinary disorders: hematuria.
Reproductive system and breast disorders: gynecomastia, breast tenderness, erectile dysfunction.
Metabolism and nutrition disorders: decreased appetite, weight gain.
General disorders: asthenia, edema, chest pain.
a Hepatic failure has been reported rarely in patients taking bicalutamide, but a causal relationship to the drug has not been clearly established. Periodic monitoring of liver function should be considered.
b Hepatic events were rarely severe and often reversible, decreasing or resolving with continued treatment or discontinuation of treatment.
c Observed with the use of LH agonists and antiandrogens for the treatment of prostate cancer. The risk was increased with bicalutamide 50 mg in combination with LH agonists, but no increased risk was observed with bicalutamide 150 mg as monotherapy for prostate cancer.
e May decrease after castration.
Expiration date
3 years.
Storage conditions
Store in original packaging out of the reach of children.
Packaging
7 tablets in a blister, 4 blisters in a box.
10 tablets in a blister, 3 blisters in a box.
Vacation category
According to the recipe.
Producer
Location of the manufacturer and its business address
18 Eli Hurwitz St., Ind. Zone, Kfar Saba, Israel.
