BICALOX Film-coated tablet Ref.[50310] Active ingredients: Bicalutamide

Bicalutamide is well absorbed following oral administration. There is no evidence of any clinically relevant effect of food on bioavailability.

The (S)-enantiomer is rapidly cleared relative to the (R) - enantiomer, the latter having a plasma elimination half-life of about 1 week.

On daily administration of bicalutamide, the (R) - enantiomer accumulates about 10-fold in plasma as a consequence of its long half-life.

Steady state plasma concentrations of the (R) - enantiomer of approximately 9 μg/mL are observed during daily administration of 50 mg doses of bicalutamide. At steady state the predominantly active (R) - enantiomer accounts for 99% of the total circulating enantiomers.

The pharmacokinetics of the (R) - enantiomer are unaffected by age, renal impairment or mild to moderate hepatic impairment. There is evidence that for subjects with severe hepatic impairment, the (R) - enantiomer is more slowly eliminated from plasma.

Bicalutamide is highly protein bound (racemate 96%, R-bicalutamide 99.6%) and extensively metabolised (oxidation and glucuronidation); its metabolites are eliminated via the kidneys and bile in approximately equal proportions.

In a clinical study the mean concentration of R-bicalutamide in semen of men receiving 150 mg of bicalutamide was 4.9 μg/mL. The amount of bicalutamide potentially delivered to a female partner during intercourse is low and equates to approximately 0.3 μg/kg. This is below that required to induce changes in offspring of laboratory animals.

Bicalutamide is a potent antiandrogen and a mixed function oxidase enzyme inducer in animals. Target organ changes, including tumour induction and minor clinical pathology changes, are related to these activities. Enzyme induction and minor cardiac changes seen in dogs have not been observed in man. Atrophy of seminiferous tubules of the testes is a predicted class effect with anti-androgens and has been observed for all species examined. Reversal of testicular atrophy occurred 4 months after the completion of dosing in a 6-month rat study (at doses of approximately 1.5 or 0.6 times human therapeutic concentrations at the recommended dose of 50 mg or 150 mg, respectively). No recovery was observed at 24 weeks after the completion of dosing in a 12-month rat study (at doses of approximately 2 or 0.9 times human concentrations at the recommended human dose of 50 mg or 150 mg, respectively).

Following 12 months of repeated dosing in dogs (at doses of approximately 7 or 3 times human therapeutic concentrations at the recommended human dose of 50 mg or 150 mg, respectively), the incidence of testicular atrophy was the same in dosed and control dogs after a 6-month recovery period. In a fertility study (at doses of approximately 1.5 or 0.6 times human therapeutic concentrations at the recommended human dose of 50 mg or 150 mg, respectively), male rats had an increased time to successful mating immediately after 11 weeks of dosing; reversal was observed after 7 weeks off-dose.