INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo BICALOX 50 MG (film coated tablets)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

BICALOX 50 MG (film coated tablets)

COMPOSITION
Each tablet contains 50 mg
bicalutamide.

PHARMACOLOGICAL CLASSIFICATION
A 21.12 Hormone inhibitors

PHARMACOLOGICAL ACTION
Pharmacodynamic Properties
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 results from this inhibition. Bicalutamide is a racemate with its anti-androgenic activity being almost exclusively in the (R)-enantiomer.
Bicalutamide is an anti-androgen and a mixed function oxidase enzyme inducer in animals. Target organ changes, including tumour induction, in animals, are related to these activities. None of the findings in the preclinical testing is considered to have relevance to the treatment of advanced prostate cancer patients.
Pharmacokinetics
Bicalutamide is highly plasma protein bound and extensively metabolised (via oxidation and glucuronidation). Its metabolites are eliminated via the kidneys and bile in approximately equal portions.

INDICATIONS
Treatment of advanced prostate cancer in combination with Luteinising Hormone Releasing Factor (LHRF) analogue therapy or surgical castration.

CONTRA-INDICATIONS
Known hypersensitivity to bicalutamide or to any of the other ingredients of this formulation.
Females and children, including pregnant women or breastfeeding mothers.

WARNINGS
Hepatic Function Impairment
Metabolism of BICALOX 50 MG may be delayed in patients with moderate to severe hepatic function impairment, resulting in prolonged elimination half-life and increased risk of toxicity.
Periodic assessment of hepatic function should be considered during long-term use of BICALOX 50 MG.
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.

INTERACTIONS
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.
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 (see WARNINGS).
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.
BICALOX 50 MG is unlikely to impair the ability of patients to drive or operate machinery.

PREGNANCY AND LACTATION
Safety and efficacy of BICALOX 50 MG during pregnancy and lactation have not been established (see CONTRA-INDICATIONS).

DOSAGE AND DIRECTIONS FOR USE
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 LHRF 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 SPECIAL PRECAUTIONS).

SIDE EFFECTS AND SPECIAL PRECAUTIONS
Side Effects
Body as a whole
Frequent: Asthenia and hot flushes.
Less frequent: Headache, chills and fever.
The following has been reported but the frequency is unknown: Pain, abdominal pain, chest pain and pelvic pain.
Haematological System Disorders
Less frequent: Anaemia and thrombocytopenia.
The following has been reported but the frequency is unknown: Leucopenia and neutropenia.
Cardiovascular System Disorders
Less frequent: Hypertension.
The following has been reported but the frequency is unknown: Cardiovascular effects such as angina, heart failure, conduction irregularities including PR and QT interval prolongation, dysrhythmias and non-specific ECG changes; haematological disorders.
Endocrine System Disorders
Frequent: Hot flushes.
Less frequent: Gynaecomastia and breast tenderness.
The following has been reported but the frequency is unknown: Decreased libido.
Neurological System Disorders
Less frequent: Headaches, fever, mental depression, chills, and reversible neurological reactions such as nervousness, dizziness, confusion, drowsiness, insomnia and somnolence.
Gastrointestinal Disorders
Frequent: Diarrhoea, constipation and nausea.
Less frequent: Bloated feeling, indigestion, gastrointestinal or rectal bleeding, vomiting, dry mouth, loss of appetite and flatulence.
The following has been reported but the frequency is unknown: Dyspepsia and increased appetite.
Metabolic and Nutritional
Less frequent: Oedema.
The following has been reported but the frequency is unknown: Diabetes mellitus, hyperglycaemia, weight gain, weight loss and anorexia.
Musculoskeletal System Disorders
Frequent: Muscle and joint weakness; muscle weakness in hands, arms, feet and legs.
Less frequent: Neurological disorder.
Kidney/Genitourinary Disorders
Less frequent: Impotence.
The following has been reported but the frequency is unknown: Nocturia and urine discoloration.
Hepatic Disorders
Less frequent: Hepatitis or jaundice, cholestatic jaundice.
The following has been reported but the frequency is unknown: Methaemoglobinaemia, elevated levels of transaminases. The changes were frequently transient, resolving or improving despite continued therapy or following cessation of therapy. Periodic liver function testing should be considered (see Special Precautions).
Skin and Appendages Disorders
Frequent: Pruritus and dry skin.
Less frequent: Skin rash and itching of skin.
The following has been reported but the frequency is unknown: Alopecia, sweating and hirsutism.
Respiratory System Disorders
Frequent: Cough or hoarseness, runny nose, shortness of breath and sore throat.
Less frequent: Dyspnoea and tightness in chest or wheezing, flu-like syndrome and chest pain.
Other
The following has been reported but the frequency is unknown: Hypersensitivity reactions, malaise, blurred vision and anxiety.

Special Precautions
BICALOX 50 MG 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.
BICALOX 50 MG should therefore 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.
Severe hepatic changes have been observed infrequently with BICALOX 50 MG (see Side-effects).
BICALOX 50 MG therapy should be discontinued if changes are severe.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
There is no human experience of overdosage. There is no specific antidote. Treatment should be symptomatic. Dialysis may not be helpful as BICALOX 50 MG is highly protein bound and is not recovered unchanged in the urine. General supportive care, including frequent monitoring of vital signs, is indicated.

IDENTIFICATION
A white to off-white, round, film-coated, biconvex tablet engraved with “BC 50”on one face and plain on the other.

PRESENTATION
30 tablets packed into PVC/PVDC/Al blister strips in an outer cardboard carton.

STORAGE INSTRUCTIONS
Store below 30ºC.
KEEP MEDICINE OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER
41/21.12/0818

NAME AND BUSINESS ADDRESS OF HOLDER OF THE REGISTRATION CERTIFICATE
Pharmaplan (Pty) Ltd.
106 16th Road
Midrand

DATE OF PUBLICATION OF THIS PACKAGE INSERT
5 March 2009

Version: March 2009
Clinical Recommendation: 15 January 2009

New addition to this site: February 2010
Source: Pharmaceutical Industry
Launch July 2009

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