Vistamid film-coated tablets 50 mg blister No. 30

Instructions Vistamid film-coated tablets 50 mg blister No. 30

Composition

active ingredient: bicalutamide;

1 film-coated tablet contains 50 mg of bicalutamide;

excipients: lactose monohydrate; povidone; crospovidone; sodium lauryl sulfate; magnesium stearate;

shell: lactose monohydrate; hypromellose; titanium dioxide (E 171); macrogol (PEG 4000).

Dosage form

Film-coated tablets.

Main physicochemical properties: white round biconvex tablets, film-coated; engraved “VSM 50” on one side of the tablets.

Pharmacotherapeutic group

Antiandrogenic agents. ATX code L02B B03.

Pharmacological properties

Pharmacodynamics.

Bicalutamide is a nonsteroidal antiandrogen that has no other effect on the endocrine system. The drug binds to androgen receptors without activating gene expression, thus inhibiting androgenic stimuli. As a result of inhibition, regression of the prostate tumor is observed. When bicalutamide is discontinued, a certain proportion of patients may experience a withdrawal syndrome.

Bicalutamide is a racemic mixture with antiandrogenic activity, represented almost exclusively by the (R)-enantiomer.

Pharmacokinetics.

Absorption.

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

Distribution.

The (S)-enantiomer is eliminated very rapidly compared to the (R)-enantiomer; the latter has a plasma half-life of approximately 1 week.

With daily administration of bicalutamide, the (R)-enantiomer accumulates in plasma at a 10-fold concentration due to its long half-life.

A plateau concentration of the (R)-enantiomer at approximately 9 μg/ml is observed with a daily dose of 50 mg bicalutamide. At steady state, the predominantly active (R)-enantiomer accounts for 99% of the total circulating enantiomers. The pharmacokinetics of the (R)-enantiomer are independent of age, renal impairment, or mild to moderate hepatic impairment. There is evidence that the (R)-enantiomer is eliminated from plasma more slowly in patients with severe hepatic impairment.

Bicalutamide has a high degree of binding to blood proteins (racemate – 96% (R)-enantiomer – >99%) and is extensively metabolized (by oxidation and glucuronidation), its metabolites are excreted equally in urine and bile.

Elimination (extraction).

In a clinical study, the mean concentration of (R)-bicalutamide in the semen of men receiving 150 mg of bicalutamide was 4.9 μg/mL. The amount of bicalutamide that could potentially enter a woman's body during sexual intercourse is low and may be approximately 0.3 μg/mL. This level is below that which has been shown to alter the offspring in laboratory animals.

Special patient groups.

The pharmacokinetics of the (R)-enantiomer are independent of age, renal impairment, or mild to moderate hepatic impairment. There is evidence that the (R)-enantiomer is cleared from plasma more slowly in patients with severe hepatic impairment.

Indication

Treatment of advanced prostate cancer in combination with luteinizing hormone-releasing factor (LHRH) analogue therapy or surgical castration.

Contraindication

Bicalutamide is contraindicated for use in women and children.

Bicalutamide should not be administered to patients who have experienced hypersensitivity reactions to the active substance or to any of the excipients included in the medicinal product.

Concomitant use of bicalutamide with terfenadine, astemizole, or cisapride is contraindicated.

Interaction with other medicinal products and other types of interactions

There is no evidence of a pharmacodynamic or pharmacokinetic interaction between bicalutamide and luteinizing hormone-releasing factor analogues.

In vitro studies have shown that R-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 prescribing bicalutamide with drugs that may inhibit the oxidation of the drug (such as cimetidine, ketoconazole). Theoretically, this could lead to an increase in bicalutamide plasma concentrations, which could lead to increased side effects of the drug.

In vitro studies have shown that bicalutamide can displace the coumarin anticoagulant warfarin from its protein binding sites. Therefore, when bicalutamide is prescribed to patients already receiving coumarin anticoagulants, careful monitoring of prothrombin time is recommended.

In vitro studies have shown that bicalutamide can displace the coumarin anticoagulant warfarin from its protein binding sites. There have been reports of increased effects of warfarin and other coumarin anticoagulants when co-administered with bicalutamide. Therefore, careful monitoring of the IRR/PTT is recommended when bicalutamide is used in patients receiving coumarin anticoagulants, and consideration should be given to adjusting the anticoagulant dose.

Due to the fact that antiandrogen therapy may lead to QT prolongation, caution should be exercised when bicalutamide is administered concomitantly with medicinal products that may cause QT prolongation or torsade de pointes, such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmics, methadone, moxifloxacin, neuroleptics, etc. (see section 4.4).

Children.

Interaction studies have only been conducted in adult patients.

Application features

Treatment with Vistamid should be initiated under the direct supervision of a physician.

Bicalutamide is extensively metabolised in the liver. Some data suggest that in patients with severe hepatic impairment, the elimination of the drug is delayed, which may lead to accumulation of bicalutamide. Therefore, bicalutamide should be used with caution in patients with moderate or severe hepatic impairment. Due to the possibility of changes in liver function, liver function tests should be monitored periodically. Most changes occur within the first 6 months of bicalutamide use. Rarely, severe changes in liver function have been observed with bicalutamide, and fatalities have been reported (see section 4.8). If severe changes in liver function occur, bicalutamide should be discontinued.

For patients who have objective disease progression along with an elevated PSA level, discontinuation of bicalutamide therapy should be considered.

Impaired glucose tolerance has been observed in men taking luteinizing hormone-releasing factor agonists. This may manifest as diabetes mellitus or loss of glycemic control in patients with pre-existing diabetes. Therefore, caution should be exercised in monitoring blood glucose levels in patients receiving bicalutamide in combination with luteinizing hormone-releasing factor agonists.

Bicalutamide has been shown to inhibit cytochrome P450 (CYP 3A4) activity, therefore caution should be exercised when co-administered with drugs that are primarily metabolized by CYP 3A4 (see sections “Contraindications” and “Interaction with other medicinal products and other forms of interaction”).

Antiandrogen therapy may lead to prolongation of the QT interval.

In patients with risk factors or a history of QT prolongation, as well as in patients taking concomitant medications that may prolong the QT interval (see section 4.5), physicians should assess the risk/benefit ratio before initiating treatment with bicalutamide, taking into account the potential risk of torsade de pointes.

Antiandrogen therapy may cause changes in sperm morphology. Although the effect of bicalutamide on sperm morphology has not been evaluated and such changes have not been reported in patients receiving bicalutamide, patients and/or their partners should use effective contraception during treatment and for 130 days after bicalutamide therapy.

Increased effects of coumarin anticoagulants have been reported in patients receiving concomitant bicalutamide, which may lead to increases in prothrombin time (PT) and international normalized ratio (INR). Some cases have been associated with a risk of bleeding. Close monitoring of PT/INR levels is recommended and dose adjustment of anticoagulants should be considered.

Excipients.

Patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially sodium-free.

Use during pregnancy or breastfeeding

Pregnancy.

Bicalutamide is contraindicated for use in women. It is contraindicated during pregnancy.

Breast-feeding.

Bicalutamide is contraindicated during breastfeeding.

Reversible impairment of male fertility has been observed in animal studies. It should be assumed that men may also experience a period of reproductive failure or infertility.

Ability to influence reaction speed when driving vehicles or other mechanisms

Bicalutamide has no effect on the ability to drive or use machines. However, it should be borne in mind that drowsiness may occur frequently, and dizziness very commonly (see section "Adverse reactions"). Patients taking this medicine should exercise caution.

Method of administration and doses

Adult male patients, including elderly patients: orally 1 tablet 50 mg 1 time per day. Treatment with bicalutamide should be initiated at least 3 days before the start of therapy with luteinizing hormone-releasing factor analogues or simultaneously with surgical castration.

Renal insufficiency: No dose adjustment is required for patients with renal insufficiency.

Hepatic impairment: No dose adjustment is required in patients with mild hepatic impairment. Increased drug accumulation may occur in patients with moderate or severe hepatic impairment.

Children: Bicalutamide is contraindicated for use in children.

Overdose

There are no data on overdose in humans. There is no specific antidote; treatment is symptomatic. Dialysis may be ineffective because bicalutamide is highly protein bound and is not recovered unchanged in the urine. In case of overdose, general supportive care is indicated, including monitoring of vital signs.

Side effects

Adverse reactions are listed by frequency: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, ≤1/100), rare (≥1/10000, ≤1/1000), very rare (≤1/10000), frequency unknown (frequency cannot be estimated from the available data).

1 Hepatic changes are rarely severe and often resolve or improve with continued treatment or after discontinuation.

2 Included in the list of adverse drug reactions after review of post-marketing data. The frequency was determined from the frequency of reports of adverse events of hepatic failure in patients treated in the open-label Early Prostate Cancer programme (EPC) trials in the bicalutamide 150 mg groups.

3 May be reduced with concomitant castration.

4 Observed in a pharmacoepidemiological study of the use of luteinizing hormone-releasing factor agonists and antiandrogens for the treatment of prostate cancer. The risk was increased when bicalutamide 50 mg was used in combination with luteinizing hormone-releasing factor agonists, but no increased risk was observed when bicalutamide 150 mg was used as monotherapy for the treatment of prostate cancer.

Increased PC/INR: Post-marketing reports have reported interactions between coumarin anticoagulants and bicalutamide.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Expiration date

5 years.

Storage conditions

Does not require any special storage conditions. Keep out of the reach of children.

Packaging

10 tablets in a blister; 3 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

Sinton Hispania, S. L.

Address

Calle C/Castello, no. 1, Sant Boi de Llobregat, Barcelona, 08830, Spain.