Bicalutamide 50mg Calutide-50

[Drug Name]

Generic Name: Bicalutamide Tablets

[Main Ingredient] The main ingredient of this product is bicalutamide.

[Composition]

Chemical Name: N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide

Molecular Formula: C18H14F4N2O4S

[Description] This product is a white film-coated tablet; the core appears white after the coating is removed.

[Indications] Used in combination with luteinizing hormone-releasing hormone (LHRH) analogues or surgical castration for the treatment of advanced prostate cancer.

[Specification] 50mg × 10 tablets

[Dosage and Administration] Adults: Adult males, including the elderly: One tablet (50mg) once daily. Treatment with this product should commence at the same time as treatment with LHRH analogues or surgical castration. Children: This product is contraindicated in children. Renal Impairment: No dosage adjustment is required for patients with renal impairment. Hepatic Impairment: No dosage adjustment is required for patients with mild hepatic impairment; however, drug accumulation may occur in patients with moderate to severe hepatic impairment (see Precautions).

[Adverse Reactions] This product is generally well-tolerated, and discontinuation due to adverse reactions is rare. The pharmacological action of this product may cause certain expected reactions, including hot flushes, pruritus, breast tenderness, and gynecomastia; these symptoms may be alleviated by castration. This product may also cause diarrhea, nausea, vomiting, asthenia, and dry skin. Changes in liver function (elevated transaminase levels, jaundice) have been observed in clinical trials of this product; severe changes are rare, and such alterations are often transient. These changes may gradually resolve or improve whether treatment is continued or discontinued. Hepatic failure has very rarely occurred in patients treated with this product, and a causal relationship has not been established. Periodic monitoring of liver function should be considered. (See ‘Precautions’ section) Cardiovascular effects such as angina, heart failure, conduction disturbances (including PR and QT interval prolongation), arrhythmias, and non-specific ECG changes have rarely been observed. Thrombocytopenia has rarely been reported. The following side effects were also observed during clinical studies involving the co-administration of this product with LHRH analogues (considered by investigators to be possibly drug-related, with an incidence >1%). No causal relationship between these side effects and the use of the drug has been established; some are inherent to the elderly population. Cardiovascular system: heart failure. Digestive system: anorexia, dry mouth, dyspepsia, constipation, flatulence. Central nervous system: dizziness, insomnia, somnolence, decreased libido. Respiratory system: dyspnea. Genitourinary system: impotence, nocturia. Hematology: anemia. Skin and appendages: alopecia, rash, sweating, hypertrichosis. Metabolism and nutrition: diabetes mellitus, hyperglycemia, peripheral edema, weight gain, weight loss. General: abdominal pain, chest pain, headache, pelvic pain, chills.

【Contraindications】 This product is contraindicated in women and children. It must not be used in patients hypersensitive to the drug. It must not be used concomitantly with terfenadine, astemizole, or cisapride.

【Precautions】 This product is extensively metabolized in the liver. Data indicate that drug clearance may be slowed in patients with severe hepatic impairment, potentially leading to accumulation. Therefore, this product should be used with caution in patients with moderate to severe hepatic impairment. Due to the potential for hepatic changes, periodic liver function monitoring should be considered. Major changes generally occur within the first 6 months of treatment. Severe hepatic changes are rare during treatment with this product (see [Potential Adverse Reactions]). Treatment should be discontinued if severe changes occur. This product has been shown to inhibit cytochrome P450 (CYP3A4) activity; therefore, caution should be exercised when co-administering with drugs primarily metabolized by CYP3A4 (see [Contraindications] and [Drug Interactions] sections). Effects on the ability to drive and operate machinery: This product does not affect the patient's ability to drive or operate machinery. However, as drowsiness may occasionally occur, patients who have experienced such effects should exercise caution. Please read the package insert carefully and use the product under medical supervision.

【Use in Children】 Contraindicated in children.

【Use in Elderly Patients】 Please refer to the detailed description in the "Dosage and Administration" section.

【Use in Pregnant and Lactating Women】 This product is contraindicated in women; it must not be used by pregnant or lactating women.

【Drug Interactions】 There are no pharmacodynamic or pharmacokinetic interactions between this product and LHRH analogues. In vitro studies indicate that R-bicalutamide is an inhibitor of CYP3A4 and has a minor inhibitory effect on CYP2C9, CYP2C19, and CYP2D6 activities. Although no evidence of potential drug interaction was found in clinical studies using antipyrine as a marker for cytochrome P450 (CYP) activity, mean midazolam exposure (AUC) increased by 80% following 28 days of co-administration with this product. This degree of increase may be clinically relevant for drugs with a narrow therapeutic index. Therefore, co-administration with terfenadine, astemizole, or cisapride is contraindicated, and caution should be exercised when this product is used concomitantly with ciclosporin or calcium channel blockers. Dose reductions of these drugs may be required, particularly if signs of increased drug effect or adverse reactions appear. For ciclosporin, close monitoring of plasma concentrations and clinical status is recommended upon initiation or discontinuation of treatment with this product. Caution should be exercised when this product is used concomitantly with other drugs that inhibit drug oxidation, such as cimetidine and ketoconazole. Theoretically, this could lead to increased plasma concentrations of this product, potentially increasing the risk of side effects. In vitro studies suggest that this product may displace coumarin anticoagulants (e.g., warfarin) from their protein-binding sites. Therefore, close monitoring of prothrombin time is recommended for patients already receiving coumarin anticoagulants if treatment with this product is initiated.

【Overdose】 There is no experience with overdose in humans. There is no specific antidote; treatment should be symptomatic. Dialysis may not be beneficial. As the drug is highly protein-bound and not excreted in the urine as the unchanged parent compound, general supportive care—including close monitoring of vital signs—is required.

【Pharmacology and Toxicology】 Pharmacological Action: This product is a non-steroidal anti-androgen that lacks other endocrine activities. It binds to androgen receptors without activating gene expression, thereby inhibiting androgenic stimulation and leading to the regression of prostatic tumors. Clinically, discontinuation of the drug may induce an anti-androgen withdrawal syndrome in some patients. The product is a racemate; its anti-androgenic activity resides solely in the (R)-enantiomer. Toxicology: This product is a potent anti-androgen and acts as a mixed-function oxidase inducer in animals. Changes in target organs and tumor induction observed in animals are associated with these effects. Preclinical findings are considered irrelevant to the treatment of patients with advanced prostate cancer.

【Pharmacokinetics】 The drug is well absorbed following oral administration. There is no evidence of any clinically significant effect of food on its bioavailability. The (S)-enantiomer is eliminated more rapidly than the (R)-enantiomer; the latter has a plasma elimination half-life of one week. With daily dosing, the (R)-enantiomer accumulates approximately 10-fold in plasma due to its long half-life. At a daily dose of 50 mg, the steady-state plasma concentration of the (R)-enantiomer is approximately 9 μg/mL, and the active (R)-enantiomer accounts for 99% of the total circulating drug at steady state. The pharmacokinetics of the (R)-enantiomer are unaffected by age, renal impairment, or mild to moderate hepatic impairment. Evidence suggests that plasma clearance of the (R)-enantiomer is slower in cases of severe hepatic impairment. The drug is highly protein-bound (96% for the racemate; 99.6% for R-bicalutamide) and extensively metabolized (via oxidation and glucuronidation); metabolites are eliminated via renal and biliary routes in approximately equal proportions.

【Storage】 Store below 30°C. Specifications

Product Name: Bicalutamide Tablets 50mg (Calutide-50)

Common Name: Bicalutamide Tablets

Active Ingredient: Bicalutamide

Dosage Form: Tablet

Specification: 50mg × 10 tablets

Manufacturer: Cipla

Indications: For the treatment of advanced prostate cancer in combination with LHRH analogues or surgical castration.

Dosage and Administration: Adults (including the elderly): One tablet (50mg) once daily. Treatment with this product should commence at the same time as treatment with LHRH analogues or surgical castration. Children: Contraindicated in children. Renal Impairment: No dosage adjustment is required for patients with renal impairment. Hepatic Impairment: No dosage adjustment is required for patients with mild hepatic impairment; however, drug accumulation may occur in patients with moderate to severe hepatic impairment (see Precautions).