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

Bicalutamide is extensively metabolised in the liver. Data suggest that its elimination may be slower in subjects with severe hepatic impairment and this could lead to increased accumulation of bicalutamide. Therefore, BICALOX 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 BICALOX therapy.

Severe hepatic changes have been observed rarely with BICALOX, and fatal outcomes have been reported (see section 4.8). BICALOX therapy should be discontinued if changes are severe.

A reduction in glucose tolerance has been observed in males receiving LHRH agonists. 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 BICALOX in combination with LHRH agonists.

BICALOX has shown to inhibit cytochrome P450 (CYP 3A4), as such caution should be exercised when co-administered with drugs metabolised predominantly by CYP 3A4 (see sections 4.3 and 4.5).

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 BICALOX. In patients with a history of or who have risk factors for QT prolongation and in patients receiving concomitant medicinal products that may prolong the QT interval (see section 4.5) physicians should assess the benefit risk ratio including the potential for Torsade de Pointes prior to initiating BICALOX.

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 BICALOX, patients and/or their partners should use adequate contraception methods during and for 130 days after BICALOX therapy.

Potentiation of coumarin anticoagulant effects have been reported in patients receiving concomitant BICALOX therapy, which may result 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 sections 4.5 and 4.8).

There is no evidence of any pharmacodynamic or pharmacokinetic interactions between bicalutamide and GnRH analogues.

In vitro studies have shown that R-bicalutamide is an inhibitor of CYP3A4, with lesser inhibitory effects on CYP 2C9, 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 section 4.3) and caution should be exercised with the co-administration of bicalutamide with compounds such as ciclosporin and calcium channel blockers. Dosage reduction may be required for these drugs particularly if there is evidence of enhanced or adverse drug effect. For ciclosporin, 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 which may inhibit drug oxidation e.g. cimetidine and ketoconazole. In theory, this could result in increased plasma concentrations 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 started in patients who are already receiving coumarin anticoagulants, PT/INR should be closely monitored and adjustment of anticoagulant dose considered (see sections 4.4 and 4.8).

Although there is no evidence of any pharmacodynamic or pharmacokinetic interactions between bicalutamide and LHRH agonists at steady state, bicalutamide 50 mg may prevent the harmful clinical consequences of flare associated with the start of LHRH agonist therapy.

Since androgen deprivation treatment may prolong the QT interval, the concomitant use of BICALOX with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de Pointes should be carefully evaluated (see section 4.4).

Pregnancy

BICALOX is contraindicated in females and must not be given to pregnant women.

Breast-feeding

BICALOX is contraindicated in females and must not be given to nursing mothers.

Fertility

Reversible impairment of male fertility has been observed in animal studies (see section 5.3).

A period of subfertility or infertility should be assumed in man.

During treatment with BICALOX, somnolence has been reported and those patients who experience this symptom should observe caution when driving or using machines.

Unless specified, the following frequency categories were assigned based on the incidence of the adverse event in the 50 mg bicalutamide plus LHRH analogue arm of the pivotal LHRH combination study.

^a May be reduced by concomitant castration.
^b Hepatic changes are rarely severe and were frequently transient, resolving or improving with continued therapy or following cessation of therapy.
^c Listed as an adverse drug reaction following review of post-marketed data. Frequency has been determined from the incidence of reported adverse events of interstitial pneumonia in the randomised treatment period of the 150 mg EPC studies.
^d Listed as an adverse drug reaction following review of post-marketed data. Frequency has been determined from the incidence of reported adverse events of hepatic failure in patients receiving treatment in the open-label bicalutamide arm of the 150 mg EPC studies.
^e Observed in a pharmaco-epidemiology study of LHRH agonists and anti-androgens used in the treatment of prostate cancer. The risk appeared to be increased when bicalutamide 50 mg was used in combination with LHRH agonists.

Increased PT/INR: Accounts of coumarin anticoagulants interacting with bicalutamide have been reported in post marketing surveillance (see sections 4.4. and 4.5).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected reactions https://nzphvc.otago.ac.nz/reporting/

Not applicable.