Bicalaccord

New Zealand - English - Medsafe (Medicines Safety Authority)

Buy It Now

Active ingredient:
Bicalutamide 50 mg
Available from:
Teva Pharma (New Zealand) Limited
INN (International Name):
Bicalutamide 50 mg
Dosage:
50 mg
Pharmaceutical form:
Film coated tablet
Composition:
Active: Bicalutamide 50 mg Excipient: Hypromellose E-5 Lactose monohydrate Macrogol 400 Magnesium stearate Povidone Purified water   Sodium starch glycolate Titanium dioxide
Units in package:
Blister pack, PVC/PVdC Al, 28 tablets, 28 tablets
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Hetero Labs Limited
Therapeutic indications:
Treatment of advanced prostate cancer in combination with GnRH (LHRH) agonist therapy or surgical castration. Prevention of disease flare associated with the use of LHRH agonists.
Product summary:
Package - Contents - Shelf Life: Blister pack, PVC/PVdC Al, 28 tablets - 28 tablets - 36 months from date of manufacture stored at or below 25°C
Authorization number:
TT50-8433
Authorization date:
2009-09-16

Version 1.0

NEW ZEALAND DATA SHEET

1.

PRODUCT NAME

Bicalaccord, 50 mg film-coated tablets

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 50 mg of Bicalutamide.

3.

PHARMACEUTICAL FORM

Film-coated tablets

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

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.

4.2

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.

Children

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

accumulation

occur

patients

with

moderate

severe

hepatic

impairment

(see

WARNINGS AND PRECAUTIONS).

4.3

Contraindications

BICALACCORD is contraindicated in females and children.

BICALACCORD must not be given to any patient who has shown a hypersensitivity reaction

to its use.

4.4

Special warnings and precautions for use

BICALACCORD

extensively

metabolised

liver.

basis

currently

available

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.

Version 1.0

4.5

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.

Although

in vitro

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

significance.

In vitro

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.

4.6

Fertility, pregnancy and lactation

BICALACCORD is contraindicated in females and must not be given to pregnant women or nursing

mothers.

4.7

Effects on ability to drive and use machines

BICALACCORD is unlikely to impair the ability of patients to drive or operate machinery.

4.8

Undesirable effects

Bicalutamide in general, has been well tolerated with few withdrawals due to adverse events.

Post Marketing

Table 1 Frequency of Adverse Events

Frequency

System Organ Class

Event

Very common

(≥10%)

Reproductive system and breast

disorders

General disorders

Breast tenderness

, gynaecomastia

Hot flushes

Common

(≥1% and

<10%)

Gastrointestinal disorders

Hepato-biliary disorders

General disorders

Diarrhoea, nausea

Hepatic changes (elevated levels of

transaminases, jaundice)

Asthenia, pruritus

Uncommon

(≥0.1% and

<1%)

Immune system disorders

Respiratory, thoracic and

mediastinal disorders

Hypersensitivity reactions, including

angioneurotic oedema and urticaria

Interstitial lung disease

Rare

(≥0.01% and

<0.1%)

Gastrointestinal disorders

Hepato-biliary disorders

Skin and subcutaneous tissue

disorders

Vomiting

Hepatic failure

Dry skin

Version 1.0

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).

Clinical Trials

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

analogue.

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

Adverse Event

Treatment Group

Number of Patients (%)

Bicalutamide Plus GnRH

Analogue

(n=401)

Flutamide Plus

GnRH Analogue

(n=407)

Body as a Whole

Pain (General)

109 (27)

93 (23)

Back Pain

62 (15)

68 (17)

Asthenia

60 (15)

69 (17)

Pelvic Pain

52 (13)

46 (1)

Infection

41 (10)

35 (9)

Abdominal pain

33 (8)

31 (8)

Chest Pain

24 (6)

20 (5)

Headache

17 (4)

20 (5)

Flu Syndrome

16 (4)

20 (5)

Cardiovascular

Version 1.0

Hot Flushes

196 (49)

202 (50)

Hypertension

21 (5)

18 (4)

Digestive

Constipation

67 (17)

50 (12)

Nausea

44 (11)

45 (11)

Diarrhoea

40 (10)

98 (24)

Increased Liver Enzyme Test+

25 (6)

40 (10)

Flatulence

22 (5)

6 (4)

Vomiting

12 (3)

20 (5)

Haemic and Lymphatic

Anaemia #

29 (7)

35 (9)

Metabolic and Nutritional

Peripheral Oedema

34 (8)

28 (7)

Hyperglycaemia

20 (5)

16 (4)

Weight Loss

16 (4)

20 (5)

Musculoskeletal

Bone Pain

18 (4)

26 (6)

Nervous System

Dizziness

30 (7)

27 (7)

Paraesthesia

24 (6)

27 (7)

Insomnia

19 (5)

30 (7)

Respiratory System

Dypsnoea

30 (7)

24 (6)

Skin and Appendages

Rash

25 (6)

20 (5)

Version 1.0

Sweating

23 (6)

18 (4)

Urogenital

Nocturia

35 (9)

43 (11)

Haematuria

30 (7)

20 (5)

Urinary Tract Infection

26 (6)

24 (6)

Impotence

20 (5)

29 (7)

Gynaecomastia

19 (5)

23 (6)

Urinary Incontinence

9 (2)

20 (5)

+ 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.

Cardiovascular:

Angina, pectoris, congestive heart failure.

Digestive:

Anorexia, dyspepsia, rectal haemorrhage, dry mouth, melaena.

Endocrine:

Breast pain.

Metabolic

and

Nutritional:

Diabetes

mellitus,

alkaline

phosphatase

increased,

weight

gain,

creatinine increased, dehydration, gout.

Musculoskeletal:

Myasthenia, arthritis, myalgia, leg cramps, pathological fracture.

Nervous:

Anxiety, depression, libido decreased, hypertonia, confusion, neuropathy, somnolence,

nervousness.

Respiratory:

Cough increased, pharyngitis, bronchitis, pneumonia, rhinitis, lung disorder.

Skin and Appendages:

Dry skin, pruritus, alopecia, injection site reaction, hirsutism.

Urogenital:

Urinary frequency, urination impaired, dysuria, urinary retention, urinary urgency.

Haematological:

Anaemia.

Abnormal

Laboratory

Test

Values:

Laboratory

abnormalities

included

elevated

AST,

ALT,

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

groups.

Version 1.0

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

first

months

bicalutamide

therapy.

Periodic

liver

function

testing

should

considered;

particularly during the first 6 months of therapy and if patients have pre-existing hepatic abnormality.

(see Warnings and Precautions).

4.9

Overdose

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.

5.

PHARMACOLOGICAL PROPERTIES

5.1

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. 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-

enantiomer.

5.2

Pharmacokinetic properties

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

highly

protein

bound

(racemate

96%,

R-bicalutamide

99.6%)

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 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.

5.3

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

Version 1.0

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

cancer patients.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Lactose monohydrate

Sodium Starch Glycolate

Povidone

Magnesium Stearate

Hypromellose

Macrogol 400

Titanium Dioxide

6.2

Incompatibilities

Not Applicable.

6.3

Shelf life

3 years

6.4

Special precautions for storage

Store below 25°C.

6.5

Nature and contents of container

BICALACCORD 50 mg tablets, blister pack 28 tablets.

6.6

Special precautions for disposal

No special precautions for disposal.

7.

MEDICINE SCHEDULE

Prescription Medicine.

8.

SPONSOR

Teva Pharma (New Zealand) Limited

PO Box 128 244

Remuera

Auckland 1541

Telephone: 0800 800 097

9.

DATE OF FIRST APPROVAL

March 2010

10.

DATE OF REVISION OF THE TEXT

5 April 2017

SUMMARY TABLE OF CHANGES

Section changed

Summary of new information

Sponsor company name and address details updated

Similar products

Search alerts related to this product

Share this information