New Zealand - English - Medsafe (Medicines Safety Authority)
NEW ZEALAND DATA SHEET
Bicalaccord, 50 mg film-coated tablets
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 50 mg of Bicalutamide.
Treatment of advanced prostate cancer in adult males aged 18 years and older in combination with
GnRH (LHRH) agonist therapy or surgical castration. Prevention of disease flare associated with the
use of LHRH agonists.
Dose and method of administration
As combination therapy in Adult males including the elderly
One tablet (50 mg) once a day.
Treatment with BICALACCORD should be started at the same time as treatment with a
GnRH (LHRH) agonist or surgical castration.
BICALACCORD is contraindicated in children.
Use in adult males with renal impairment
No dosage adjustment is necessary for patients with renal impairment.
Use in adult males with hepatic impairment
No dosage adjustment is necessary for patients with mild hepatic impairment. Increased
WARNINGS AND PRECAUTIONS).
BICALACCORD is contraindicated in females and children.
BICALACCORD must not be given to any patient who has shown a hypersensitivity reaction
to its use.
Special warnings and precautions for use
investigations, there may be slower excretion and accumulation of bicalutimide in instances of severe
hepatic impairment. Caution is therefore required with patients with moderate to severe hepatic
impairment. In these cases regular liver function tests (bilirubin, transaminases, alkaline phosphatase)
must be carried out.
Severe hepatic changes and hepatic failure have been observed rarely with BICALACCORD (see
ADVERSE EFFECTS). If there is clinical and/or biochemical evidence of severe hepatotoxicity,
consideration should be given to discontinue BICALACCORD therapy.
Interaction with other medicines and other forms of interaction
There is no evidence of any pharmacodynamic or pharmacokinetic interactions between bicalutmaide
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.
studies have suggested the potential for bicalutamide to inhibit cytochrome 3A4, a
number of clinical studies show the magnitude of any inhibition is unlikely to be of clinical
studies have shown that bicalutamide can displace the coumarin anticoagulant, warfarin, from
its protein binding sites. It is therefore recommended that if BICALACCORD is started in patients
who are already receiving coumarin anticoagulants, prothrombin time should be closely monitored.
Although there is no evidence of any pharmacodynamic or pharmacokinetic interactions between
bicalutamide 50 mg and LHRH agonists at steady state, BICALACCORD 50 mg may prevent the
harmful clinical consequences of flare associated with the start of LHRH agonist therapy.
Fertility, pregnancy and lactation
BICALACCORD is contraindicated in females and must not be given to pregnant women or nursing
Effects on ability to drive and use machines
BICALACCORD is unlikely to impair the ability of patients to drive or operate machinery.
Bicalutamide in general, has been well tolerated with few withdrawals due to adverse events.
Table 1 Frequency of Adverse Events
System Organ Class
Reproductive system and breast
Hepatic changes (elevated levels of
Immune system disorders
Respiratory, thoracic and
Hypersensitivity reactions, including
angioneurotic oedema and urticaria
Interstitial lung disease
Skin and subcutaneous tissue
May be reduced by concomitant castration.
Hepatic changes are rarely severe and were frequently transient, resolving or improving with
continued therapy or following cessation of therapy (see WARNINGS AND PRECAUTIONS).
In patients with advanced prostate cancer treated with Bicalutamide in combination with an GnRH
analogue, the most frequent adverse experience was hot flushes (49%).
Diarrhoea was the adverse event most frequently leading to treatment withdrawal: 6% of the patients
treated with flutamide-GnRH analogue and 0.5% of the patients treated with bicalutamide-GnRH
In the multicentre, double-blind, controlled clinical trial comparing bicalutamide 50 mg once daily
with flutamide 250 mg three times a day, each in combination with a GnRH analogue, the following
adverse experiences with an incidence of 5% or greater, regardless of causality, have been reported.
Incidence of Adverse Events
(≥5% in Either Treatment Group)
Regardless of Causality
Number of Patients (%)
Bicalutamide Plus GnRH
Body as a Whole
Increased Liver Enzyme Test+
Haemic and Lymphatic
Metabolic and Nutritional
Skin and Appendages
Urinary Tract Infection
+ Increased liver enzymes tests, includes increased AST, ALT or both
# Anaemia includes anaemia, hypochromic and iron deficiency anaemia
Other less frequent (greater than or equal to 2%, but less than 5%) adverse experiences reported in the
bicalutamide-GnRH analogue treatment group are listed below by body system and are in order of
decreasing frequency within each body system regardless of causality. Some of these are commonly
reported in elderly patients.
Body as a whole:
Oedema, neoplasm, fever, neck pain, chills, sepsis.
Angina, pectoris, congestive heart failure.
Anorexia, dyspepsia, rectal haemorrhage, dry mouth, melaena.
creatinine increased, dehydration, gout.
Myasthenia, arthritis, myalgia, leg cramps, pathological fracture.
Anxiety, depression, libido decreased, hypertonia, confusion, neuropathy, somnolence,
Cough increased, pharyngitis, bronchitis, pneumonia, rhinitis, lung disorder.
Skin and Appendages:
Dry skin, pruritus, alopecia, injection site reaction, hirsutism.
Urinary frequency, urination impaired, dysuria, urinary retention, urinary urgency.
bilirubin, BUN and creatinine and decreased haemoglobin and white cell count have been reported in
both bicalutamide-GnRH analogue treated and flutamide-GnRH analogue treated patients. Increased
liver enzyme tests and decreases in haemoglobin were reported less frequently in the bicalutamide
plus GnRH analogue group. Other changes were reported with similar incidences in both treatment
Hepatic changes (elevated levels of transaminases, jaundice) have been observed in clinical trials with
bicalutamide. The changes were frequently transient, resolving or improving despite continued
therapy or following cessation of therapy. The majority of the hepatic changes were seen within the
particularly during the first 6 months of therapy and if patients have pre-existing hepatic abnormality.
(see Warnings and Precautions).
There is no human experience of overdosage. There is no specific antidote; treatment should be
symptomatic. Dialysis may not be helpful, since BICALACCORD 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 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. 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-
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.
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 bicalutamide
150 mg 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.
Preclinical safety data
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. There are no preclinical findings that preclude the administration of bicalutamide to prostate
List of excipients
Sodium Starch Glycolate
Special precautions for storage
Store below 25°C.
Nature and contents of container
BICALACCORD 50 mg tablets, blister pack 28 tablets.
Special precautions for disposal
No special precautions for disposal.
Teva Pharma (New Zealand) Limited
PO Box 128 244
Telephone: 0800 800 097
DATE OF FIRST APPROVAL
DATE OF REVISION OF THE TEXT
5 April 2017
SUMMARY TABLE OF CHANGES
Summary of new information
Sponsor company name and address details updated