Biluron 50

White, round, biconvex film-coated tablet. The tablet is debossed with "BCM 50" on one side.
Each film coated tablet contains 50 mg Bicalutamide.
Excipients/Inactive Ingredients: Tablet core: Lactose, Sodium Starch Glycolate, Povidone, Crospovidone, Sodium lauryl sulfate, Magnesium Stearate.
Tablet coating: Lactose, Hypromellose, Titanium dioxide, Macrogol 4000.

Pharmacotherapeutic Group: Antiandrogen. ATC code: L02 B B03.
Pharmacology: Pharmacodynamics: Bicalutamide is a non-steroidal anti-androgen, devoid of other endocrine activity. It binds to androgen receptors without activating gene expression, and thus inhibits the androgen stimulus. Regression of prostatic tumours result from this inhibition. Clinically discontinuation of Bicalutamide can result in antiandrogen withdrawal syndrome in a subset of patients. Bicalutamide is a racemate with its antiandrogenic activity being almost exclusively in the (R)-enantiomer.
Pharmacokinetics: The pharmacokinetics parameters of 68 subjects (72 subjects were included in the study, and 69 completed the study, 1 subject was dropped before analyses to keep the study balanced) were calculated and results were statistically analyzed to demonstrate bioequivalence in a one period parallel bioequivalence study. After oral administration of Bicalutamide 50 mg film coated tablets (test product) the mean of the maximum plasma concentration (C_max) (rate of absorption) was 913.0 ng/mL. The median T_max was 33.95 h. The extent of absorption is expressed in Area Under the Curve (AUC)_0-72 and AUC_0-inf the mean values were 176329.8 ng·h/mL and 183372.6 ng·h/mL respectively. The mean elimination half life (T_¹/2) of Bicalutamide 50 mg film coated tablets was 120.51 h.
The ratios and confidence intervals between test and reference product were as following: for C_max the ratio was 94.39% (88.20%-101.01%). For AUC_0-72 the ratio was 93.42% (84.01%-103.89%). The results of the study showed that the ratios and confidence intervals are within the acceptance range for bioequivalence, therefore it can be concluded that the test product, Bicalutamide 50 mg film coated tablets, is bioequivalence with the reference product.

Treatment of advanced prostate cancer in combination with Luteinizing Hormone Releasing Hormone (LHRH) analogue therapy or surgical castration.

Adults: Adult males including the elderly: One tablet (50 mg) once a day. Treatment with Bicalutamide should be started at least 3 days before commencing treatment with an LHRH analogue, or at the same time as surgical castration.
Children: Bicalutamide is contraindicated in children (see Contraindications).
Renal Impairment: No dosage adjustment is necessary for patients with renal impairment.
Hepatic Impairment: No dosage adjustment is necessary for patients with mild hepatic impairment.
Increased accumulation may occur in patient with moderate to severe hepatic impairment (see Precautions).

There is no human experience of overdosage. There is no specific antidote; treatment should be symptomatic. Dialysis may not be helpful, since Bicalutamide is highly protein bound and is not recovered unchanged in the urine. General supportive care, including frequent monitoring of vital signs is indicated.

Bicalutamide is contraindicated in females and children (see Use in Pregnancy & Lactation).
Bicalutamide must not be given to any patient who has shown a hypersensitivity reaction to the active substance or to any of the excipients of this product.
Co-administration of terfenadine, astemizole or cisapride with Bicalutamide is contraindicated (see Interactions).

Initiation of treatment should be under the direct supervision of a specialist.
Bicalutamide is extensively metabolised in the liver. Data suggest that its elimination may be slower in patients with severe hepatic impairment and this could lead to increased accumulation of Bicalutamide. Therefore Bicalutamide should be used with caution in patients with moderate to severe hepatic impairment.
Periodic liver function testing should be considered due to the possibility of hepatic changes. The majority of changes are expected to occur within the first 6 months of Bicalutamide therapy.
Severe hepatic changes and hepatic failure have been observed rarely with Bicalutamide, and fatal outcomes have been reported (see Adverse Reactions).
Bicalutamide therapy should be discontinued if changes are severe. A reduction in glucose tolerance has been observed in males receiving LHRH agonist. This may manifest as diabetes or loss of glycaemic control in those with pre-existing diabetes.
Consideration should therefore be given to monitoring blood glucose in patients receiving Bicalutamide in combination with LHRH agonist.
Bicalutamide has been shown to inhibit cytochrome P450 (CYP3A4), as such caution should be exercised when co-administrated with drugs metabolised predominantly by CYP3A4 (see Contraindications and Interactions).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Androgen deprivation therapy may prolong the QT interval, although a causal association has not been established with Bicalutamide. In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval (see Interactions) physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating Bicalutamide.
Antiandrogen therapy may cause morphological changes in spermatozoa. Although the effect of Bicalutamide on sperm morphology has not been evaluated and no such changes have been reported for patients who received Bicalutamide, patients and/or their partners should follow adequate contraception during and for 130 days after Bicalutamide therapy.
Potentiation of coumarin anticoagulant effects have been reported in patients receiving concomitant Bicalutamide therapy, which may results in increased Prothrombin Time (PT) and International Normalised Ratio (INR). Some cases have been associated with risk of bleeding. Close monitoring of PT/INR is advised and anticoagulant dose adjustment should be considered (see Interactions and Adverse Reactions).
Effects on ability to drive and use machines: Bicalutamide is unlikely to impair the ability of patients to drive or operate machinery. However, it should be noted that occasionally somnolence may occur. Any affected patients should exercise caution.

Pregnancy: Bicalutamide is contra-indicated in females and must not be given to pregnant women.
Breast-feeding: Bicalutamide is contra-indicated during breast feeding.
Fertility: Reversible impairment of male fertility has been observed in animal studies. A period of subfertility or infertility should be assumed in man.

(See table.)


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It has been reported that the accounts of coumarin anticoagulant interacting with Bicalutamide can increase PT/INR (see Precautions and Interactions).

There is no evidence of any pharmacodynamic or pharmacokinetic interactions between Bicalutamide and LHRH analogues. In vitro studies have shown that R-bicalutamide is an inhibitor of CYP3A4, with lesser inhibitory effects on CYP2C9, 2C19 and 2D6 activity.
Although clinical studies using antipyrine as a marker of cytochrome P450 (CYP) activity showed no evidence of a drug interaction potential with Bicalutamide, mean midazolam exposure (AUC) was increased by up to 80%, after co-administration of Bicalutamide for 28 days. For drugs with a narrow therapeutic index such an increase could be of relevance. As such, concomitant use of terfenadine, astemizole and cisapride is contraindicated (see Contraindications) and caution should be exercised with the co-administration of Bicalutamide with compounds such as cyclosporin and calcium channel blockers. Dosage reduction may be required for these drugs particularly if there is evidence of enhanced or adverse drug effect. For cyclosporin, it is recommended that plasma concentrations and clinical condition are closely monitored following initiation or cessation of Bicalutamide therapy.
Caution should be exercised when prescribing Bicalutamide with other drugs with may inhibit drug oxidation e.g. cimetidine and ketoconazole. In theory, this could result in increased plasma concentration of Bicalutamide, which theoretically could lead to an increase in side effects.
In vitro studies have shown that Bicalutamide can displace the coumarin anticoagulant, warfarin, from its protein binding sites. There have been reports of increased effect of warfarin and other coumarin anticoagulants when co-administered with Bicalutamide. It is therefore recommended that if Bicalutamide is administered in patients who are concomitantly receiving coumarin anticoagulants, PT/INR should be closely monitored and adjustments of anticoagulant dose considered (see Precautions and Adverse Reactions).

Store below 30°C.
Shelf Life: 3 years.

Cancer Hormone Therapy

L02BB03 - bicalutamide ; Belongs to the class of anti-androgens. Used in treatment of neoplastic diseases.

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