Bicalutamide-vista ac

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BICALUTAMIDE-VISTA AC (BICALUTAMIDE-VISTA AC)

Composition:

Active substance: bicalutamide;

1 film-coated tablet contains 50 mg of bicalutamide;

Excipients: lactose monohydrate; povidone K-25; sodium starch glycolate (type A); magnesium stearate;

tablet coating Opadry OY-S-9622: hypromellose (5 cP), titanium dioxide (E 171), propylene glycol.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: round, biconvex, white film-coated tablets.

Pharmacotherapeutic group. Hormonal antagonists and related agents. Antiandrogen agents. Bicalutamide. ATC code L02BB03

Pharmacological Properties

Pharmacodynamics

Bicalutamide is a non-steroidal antiandrogen with no other effects on the endocrine system. It binds to androgen receptors without activating gene expression, thereby inhibiting androgenic stimulation. As a result of this inhibition, regression of prostate tumors is observed. After discontinuation of bicalutamide, a withdrawal syndrome may occur in some patients. Bicalutamide is a racemic mixture with antiandrogenic activity residing almost exclusively in the (R)-enantiomer.

Pharmacokinetics

Absorption. Bicalutamide is well absorbed following oral administration. There is no evidence of clinically significant food effects on bicalutamide bioavailability.

Distribution. Bicalutamide is highly protein-bound (racemate 96%, (R)-enantiomer > 99%) and undergoes extensive metabolism (via oxidation and glucuronidation); its metabolites are excreted in urine and bile in approximately equal amounts.

Biotransformation. The (S)-enanti游戏副本

Clinical characteristics

Indications. To be used for the treatment of metastatic prostate cancer in combination with luteinizing hormone-releasing hormone (LHRH) analogues or surgical castration.

Contraindications

• BICALUTAMIDE-VISTA AS is contraindicated in women and children (see section "Use in pregnancy and lactation").
• Hypersensitivity to the active substance or to any of the excipients.
• Concomitant administration of BICALUTAMIDE-VISTA AS with terfenadine, astemizole, or cisapride is contraindicated (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction

There is no evidence of pharmacodynamic or pharmacokinetic interaction between bicalutamide and luteinizing hormone-releasing hormone (LHRH) analogues.

In vitro studies have shown that R-bicalutamide is an inhibitor of CYP3A4 and has a lesser inhibitory effect on the activity of CYP2C9, 2C19, and 2D6.

Although clinical studies using antipyrine as a marker for cytochrome P450 (CYP) activity did not indicate a potential interaction with bicalutamide, the mean midazolam concentration (area under the pharmacokinetic curve) increased by up to 80% when co-administered with bicalutamide for 28 days. For medicinal products with a narrow therapeutic index, such an increase may be significant. Therefore, concomitant use with terfenadine, astemizole, and cisapride is contraindicated (see section "Contraindications"). Bicalutamide should also be used with caution when administered with agents such as cyclosporine and calcium channel blockers. Dose reduction of these agents may be necessary, especially if signs of enhanced bicalutamide effects or adverse reactions occur. When cyclosporine is used, careful monitoring of its plasma concentration and the patient's clinical status is recommended upon initiation or discontinuation of bicalutamide therapy.

Bicalutamide should be prescribed with caution when used with medicinal products that may inhibit the oxidation of other agents (e.g., cimetidine, ketoconazole). Theoretically, this may lead to increased plasma concentrations of bicalutamide and result in an increased risk of adverse effects.

In vitro studies have shown that bicalutamide may displace the coumarin anticoagulant warfarin from its protein-binding sites. Enhanced effects of warfarin and other coumarin anticoagulants have been reported when administered concomitantly with bicalutamide. Therefore, during bicalutamide treatment in patients receiving coumarin anticoagulants, careful monitoring of PT (prothrombin time) and INR (international normalized ratio) is recommended, and dose adjustment of anticoagulants should be considered (see sections "Special warnings and precautions for use" and "Undesirable effects").

Since antiandrogen therapy may lead to QT interval prolongation, bicalutamide should be used with caution when administered concomitantly with medicinal products capable of prolonging the QT interval or inducing torsades de pointes ventricular tachycardia, such as class IA (quinidine, disopyramide) or class III (amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmics, methadone, moxifloxacin, neuroleptics, etc. (see section "Special warnings and precautions for use").

Children. Interaction studies have been conducted only in adults.

Special precautions for use

Treatment with this medicinal product should be initiated under direct medical supervision. Bicalutamide is actively metabolized in the liver. Available data suggest that in patients with severe hepatic impairment, elimination of bicalutamide is slowed, which may lead to its accumulation. Therefore, bicalutamide should be used with caution in patients with moderate or severe hepatic impairment. Due to the potential for changes in liver function, liver function tests should be monitored periodically. Most changes are expected to occur within the first 6 months of bicalutamide treatment. Rarely, severe hepatic dysfunction has been observed during treatment with this medicinal product, including reports of fatal cases (see section "Adverse reactions"). If severe liver function abnormalities occur, bicalutamide treatment should be discontinued. In patients who have objective disease progression together with elevated PSA (prostate-specific antigen) levels, discontinuation of bicalutamide should be considered.

In men receiving gonadotropin-releasing hormone (GnRH) agonists, glucose tolerance may be reduced. This may manifest as new-onset diabetes mellitus or loss of glycemic control in patients with pre-existing diabetes. Therefore, blood glucose levels should be monitored in patients receiving bicalutamide in combination with GnRH agonists.

Bicalutamide has been shown to inhibit CYP3A4 enzyme activity; therefore, it should be used cautiously with medicinal products that are primarily metabolized by CYP3A4 (see sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction").

Antiandrogen therapy may lead to QT interval prolongation.

In patients with risk factors or a history of QT interval prolongation, as well as in patients concurrently receiving medicinal products that may prolong the QT interval (see section "Interaction with other medicinal products and other forms of interaction"), the physician should assess the benefit-risk ratio before initiating bicalutamide treatment, considering the potential risk of developing torsade de pointes ventricular tachycardia.

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 sexual partners should use effective contraception during treatment and for 130 days after the last dose of the medicinal product.

Enhanced effects of coumarin anticoagulants have been reported in patients receiving bicalutamide concomitantly, which may lead to increased prothrombin time (PT) and international normalized ratio (INR). Some cases were associated with an increased risk of bleeding. Careful monitoring of PT/INR is recommended, and dose adjustment of anticoagulants should be considered (see sections "Interaction with other medicinal products and other forms of interaction" and "Adverse reactions").

Important information about excipients. The medicinal product contains 1.74 mg of sodium per dose, i.e., essentially sodium-free.

BICALUTAMIDE-VISTA AS contains lactose. Patients with rare hereditary forms of galactose intolerance, congenital lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Use during pregnancy and breastfeeding

Pregnancy. Bicalutamide is contraindicated for use in women and should not be administered during pregnancy.

Breastfeeding. Bicalutamide is contraindicated during breastfeeding.

Fertility. Reversible impairment of fertility in males has been observed in animal studies. A temporary period of impaired reproductive function or infertility may also be expected in men.

Ability to affect reaction speed when driving or operating machinery

The medicinal product does not affect the ability to drive a vehicle or operate machinery. However, it should be noted that somnolence is common and dizziness is very common (see section "Adverse reactions"). Patients taking this medicinal product should exercise caution.

Method of Administration and Dosage

For adult men, including elderly patients: take 1 tablet (50 mg) once daily.

Administration of bicalutamide should begin at least 3 days before starting therapy with luteinizing hormone-releasing hormone analogues or simultaneously with surgical castration.

Renal impairment: dose adjustment is not required in patients with renal impairment.
Hepatic impairment: dose adjustment is not required in patients with mild hepatic impairment.
In patients with moderate and severe hepatic impairment, increased accumulation may occur (see section "Special Warnings and Precautions for Use").

Children. The medicinal product is contraindicated for use in children.

Overdose

Symptoms. Data on overdose in humans are lacking.

Treatment. There is no specific antidote; treatment is symptomatic. Dialysis may be ineffective because bicalutamide is highly protein-bound and is not excreted unchanged in urine. In case of overdose, general supportive therapy is indicated, including monitoring of vital functions.

Side effects

The frequency of side effects is defined as follows: very common (≥ 1/10), common (from ≥ 1/100 to < 1/10), uncommon (from ≥ 1/1000 to < 1/100), rare (from ≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated based on available data).

1 Liver-related changes are rarely severe and often resolve or diminish with continued treatment or after discontinuation.

2 Included in the list of adverse drug reactions following review of post-marketing data. The frequency was determined based on the rate of reported cases of hepatic failure in patients receiving treatment in open-label EPC (Early Prostate Cancer programme) studies in the 150 mg bicalutamide groups.

3 May decrease with concomitant castration.

4 Observed in a pharmacoepidemiological study of luteinizing hormone-releasing hormone agonists and antiandrogens used in the treatment of prostate cancer. The risk increased when 50 mg bicalutamide was used in combination with luteinizing hormone-releasing hormone agonists; however, an increased risk was not observed when 150 mg bicalutamide was used as monotherapy for the treatment of prostate cancer.

5 Included in the list of adverse drug reactions following review of post-marketing data. The frequency was determined based on the rate of reported cases of interstitial pneumonia as an adverse event in patients receiving treatment in open-label EPC studies in the bicalutamide 150 mg groups.

Increased PT/INR: Reports from post-marketing surveillance have indicated an interaction between coumarin anticoagulants and bicalutamide (see sections "Dosage and Administration" and "Interaction with Other Medicinal Products and Other Forms of Interaction"). Reporting of suspected adverse reactions

Reporting of adverse reactions after drug registration is highly important. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life. 5 years.

Storage conditions. Store in the original packaging, at a temperature not exceeding 25 °C, in a place inaccessible to children.

Packaging. 10 tablets per blister, 3 blisters per cardboard pack.

Prescription status. Prescription only.

Manufacturer. JENEPHARM, S.A.

Manufacturer's address and place of business. 18th km Marathon Avenue, Pallini, 153 51, Greece