Bicalox Tablets

Treatment of advanced prostate cancer in combination with luteinizing hormone releasing hormone (LHRH) analogue therapy or surgical castration.

Posology
Adult males including the elderly: One tablet (50 mg) once a day. Treatment with Bicalox 50 mg should be started at least three days before commencing treatment with a LHRH analogue, or at the same time as surgical castration.
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 patients with moderate to severe hepatic impairment (see section 4.4).
Paediatric population
BICALOX 50 mg is contraindicated in children (see section 4.3).
Method of administration
Oral use
The tablets should be swallowed whole with liquid.

BICALOX is contraindicated in the following:
u2022 Females and children, pregnant women, or breastfeeding mothers.
u2022 BICALOX 50 mg must not be given to any patient who has known hypersensitivity to bicalutamide or to any of the other excipients.

Hepatic function impairment: BICALOX 50 mg is extensively metabolised in the liver. Data suggests that its elimination may be slower in subjects with severe hepatic impairment, and this could lead to increased accumulation of BICALOX 50 mg. Metabolism of BICALOX 50 mg may be delayed in patients with moderate to severe hepatic function impairment, resulting in a prolonged elimination half-life and increased risk of toxicity. Therefore, BICALOX 50 mg should be used with caution in patients with moderate to severe hepatic impairment.
Periodic liver function testing should be considered during long-term use of BICALOX 50 mg, 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 infrequently with BICALOX 50 mg (see section 4.8). BICALOX 50 mg therapy should be discontinued if changes are severe.
Non-Alcoholic Fatty Liver Disease (NAFLD)
Testosterone deficiency was associated with higher serum and hepatic levels of triglycerides and higher serum levels of low-density lipoprotein (LDL) in the body, with significant increases in fasting plasma glucose and insulin levels. Patients who receive androgen deprivation therapy (ADT) such as BICALOX 50 mg are at a greater risk of non-alcoholic fatty liver disease. ADT is associated with significant increase in incidences of other liver diseases such as cirrhosis, liver necrosis, and any liver disease (see section 4.8).
Medicines metabolised by cytochrome P450: Although clinical studies using antipyrine as a marker of Cytochrome P450 (CYP) activity showed no evidence of a drug interaction potential with BICALOX 50 mg, midazolam exposure (AUC) was increased by up to 80 %, after co-administration with BICALOX 50 mg for 28 days. This rise is comparable to that seen in other studies after administration of grapefruit juice. Caution should be exercised with the co-administration of BICALOX 50 mg with compounds such as these. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Luteinising hormone releasing factor (LHRF): There is no evidence of any pharmacodynamic or pharmacokinetic interactions between BICALOX 50 mg and LHRF analogues.
Ketoconazole and cimetidine: Formal interaction studies have not been undertaken, but caution should be exercised when prescribing BICALOX 50 mg with other medicines, e.g., ketoconazole and cimetidine, which may inhibit oxidation of BICALOX 50 mg. It could result in increased plasma concentrations of BICALOX 50 mg which could lead to an increase in side-effects.
Coumarin anticoagulants: BICALOX 50 mg can displace the coumarin anticoagulant, warfarin, from its protein binding sites. It is therefore recommended that if BICALOX 50 mg is started in patients, who are already receiving coumarin anticoagulants, prothrombin time should be closely monitored.

Pregnancy
BICALOX is contraindicated in females and must not be given to pregnant women (see section 4.3).
Breast-feeding
BICALOX is contraindicated in females and must not be given to nursing mothers (see section 4.3).
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 not drive or use machines.

Blood and lymphatic system disorders
Frequent: Anaemia
The following side effects have been reported but the frequencies are Unknown: Leucopenia, neutropenia, thrombocytopenia.
Immune system disorders
Less frequent: Hypersensitivity reactions (including angioneurotic oedema and urticaria)
Metabolism and nutrition disorders
Frequent: Anorexia, decreased appetite. The following side effects have been reported but the frequencies are unknown: Diabetes mellitus, hyperglycaemia.
Psychiatric disorders
Frequent: depression, decreased libido
Nervous system disorders
Frequent: Dizziness, somnolence, insomnia
Less frequent: Reversible neurological reactions such as nervousness, drowsiness, and confusion dizziness, insomnia and somnolence.
Cardiac disorders
Frequent: Myocardial infarction (fatal outcomes have been reported), cardiac failure
Vascular disorders
Frequent: Hypertension, Hot flush
Respiratory, thoracic, and mediastinal disorders
Frequent: Upper respiratory tract infection, cough or hoarseness, runny nose, shortness of breath, sore throat, and sneezing
Less frequent: Interstitial lung disease and dyspnoea. Fatal outcomes have been reported.
Gastrointestinal disorders
Frequent: Abdominal pain, constipation, nausea, dyspepsia, flatulence, diarrhoea
Less frequent: Gastro-intestinal or rectal bleeding, vomiting.
Hepato-biliary disorders
Frequent: Hepatic changes (including elevated levels of transaminases, jaundice), hepatitis
Less frequent: Hepatic failure. The following side effects have been reported but the frequencies are unknown: Methaemoglobinaemia, non-alcoholic fatty liver disease (see section 4.4).
Skin and subcutaneous tissue disorders
Frequent: Alopecia, hirsuitism/hair re-growth, dry skin, pruritis, rash, sweating
Renal and urinary disorders
Frequent: Haematuria
The following side effects have been reported but the frequencies are unknown: Nocturia
Reproductive system and breast disorders
Frequent: Gynaecomastia and breast tenderness, impotence, decreased libido, erectile dysfunction
General disorders and administration site conditions
Frequent: Asthenia, oedema, chest pain, fever, chills, flu-like syndrome
Investigations
Frequent: Weight gain
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. Health care providers are requested to report any suspected adverse reactions to SAHPRA via the Med Safety App (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. You can also report side effects to Acino Pharma via email on [email protected].

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