Bicalutamide 50 mg, 150mg Table ts TajPharma : U s es , Side Effects , In teractio ns , Pictures , W arnings , Bicaluta mide D os age & Rx Info

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Rx Paediatric population: Bicalutamide is

contraindicated for use in children (see section
Bicalutamide Tablets USP 4.3 ).

50mg/150mg Renal impairment: no dosage adjustment is

necessary for patients with renal impairment.
1. NAME OF THE MEDICINAL Hepatic impairment: no dosage adjustment is
PRODUCT necessary for patients with mild hepatic
impairment. Increased accumulation may occur
Bicalutamide Tablets USP 50mg Taj Pharma
in patients with moderate to severe hepatic
Bicalutamide Tablets USP 150mg Taj Pharma impairment (see Section 4.4).
2. QUALITATIVE AND 4.3 Contraindications
QUANTITATIVE COMPOSITION Hypersensitivity to the active substance or to
any of the excipients listed in section 6.1.
a) Each film-coated tablet contains:
Bicalutamide USP 50mg Use in females, children and adolescents is
Excipients q.s. contraindicated (see section 4.6).
Colour: Titanium Dioxide USP
Co-administration of terfenadine, astemizole or
b) Each film-coated tablet contains: cisapride with Bicalutamide is contra-indicated
Bicalutamide USP 150mg (see section 4.5).
Excipients q.s.
4.4 Special warnings and precautions for use
Colour: Titanium Dioxide USP
Initiation of treatment should be under the direct
For the full list of excipients, see section 6.1 supervision of a specialist.

3. PHARMACEUTICAL FORM Bicalutamide is extensively metabolized in the

liver. Data suggests that its elimination may be
Film-coated tablet. slower in subjects with severe hepatic
impairment and this could lead to increased
4. CLINICAL PARTICULARS accumulation of bicalutamide. Therefore,
bicalutamide should be used with caution in
4.1 Therapeutic indications patients with moderate to severe hepatic
Treatment of advanced prostate cancer in impairment.
combination with luteinizing-hormone releasing
hormone (LHRH) analogue therapy or surgical Periodic liver function testing should be
castration. considered due to the possibility of hepatic
changes. The majority of changes are expected
4.2 Posology and method of administration to occur within the first 6 months of
Posology bicalutamide therapy.
Adult males including the elderly: one tablet Severe hepatic changes and hepatic failure have
(50mg) once a day. been observed rarely with bicalutamide, and
Treatment with Bicalutamide Tablets 50mg fatal outcomes have been reported (see Section
should be started at least 3 days before 4.8).
commencing treatment with an LHRH analogue, Bicalutamide therapy should be discontinued if
or at the same time as surgical castration. changes are severe.
A reduction in glucose tolerance has been
observed in males receiving LHRH agonists.
 Bicalutamide 50 mg, 150mg Table ts TajPharma : U s es , Side Effects , In teractio ns , Pictures , W arnings , Bicaluta mide D os age & Rx Info | Bicalutamid e U s es , Side Effects - Anticancer, Bicalutamide : I ndications , Side Eff ects , W arnings , Bicalutamide - D rug Info rma tion - TajPha rma, Bicalu tamide d os e Taj pharmaceu ticals Bicalutamide in teractio ns , Taj Pharmaceu tical Bicalutamide con train dications , Bicaluta mide price, Bicalu tamide TajPha rma Anticancer Ta blets SmPC - TajP harma S tay connected to all upda ted on Bicalu tamide Taj Pha rmaceu ticals Taj pharmaceuticals Mu mbai. Patie nt Inf orma tion L eafle ts , SmPC.

This may manifest as diabetes or loss of There is no evidence of any Pharmacodynamic

glycaemic control in those with pre-existing or pharmacokinetic interactions between
diabetes. Consideration should therefore be bicalutamide and LHRH analogues.
given to monitoring blood glucose in patients
receiving bicalutamide in combination with In vitro studies have shown that R-bicalutamide
LHRH agonists. is an inhibitor of CYP 3A4, with lesser
inhibitory effects on CYP 2C9, 2C19 and 2D6
Bicalutamide has been shown to inhibit activity.
Cytochrome P450 (CYP 3A4), as such caution
Although clinical studies using antipyrine as a
should be exercised when co-administered with
drugs metabolised predominantly by CYP 3A4, marker of cytochrome P450 (CYP) activity
see Sections 4.3 and 4.5. showed no evidence of a drug interaction
potential with ' Bicalutamide', mean midazolam
Androgen deprivation therapy may prolong the exposure (AUC) was increased by up to 80%,
QT interval. after co-administration of bicalutamide for 28
days. For drugs with a narrow therapeutic index
In patients with a history of or risk factors for such an increase could be of relevance. As such,
QT prolongation and in patients receiving concomitant use of terfenadine, astemizole and
concomitant medicinal products that might cisapride is contra-indicated (see Section 4.3)
prolong the QT interval (see section 4.5)
and caution should be exercised with the co-
physicians should assess the benefit risk ratio administration of bicalutamide with compounds
including the potential for Torsade de pointes
such as cyclosporin and calcium channel
prior to initiating Bicalutamide tablets.
blockers. Dosage reduction may be required for
Antiandrogen therapy may cause morphological these drugs particularly if there is evidence of
changes in spermatozoa. Although the effect of enhanced or adverse drug effect. For
bicalutamide on sperm morphology has not been cyclosporin, it is recommended that plasma
evaluated and no such changes have been concentrations and clinical condition are closely
reported for patients who received Bicalutamide monitored following initiation or cessation of
tablets, patients and/or their partners should bicalutamide therapy.
follow adequate contraception during and for Caution should be exercised when prescribing
130 days after Bicalutamide therapy.
bicalutamide with other drugs which may inhibit
Patients with rare hereditary problems of drug oxidation e.g. cimetidine and ketoconazole.
galactose intolerance, the total lactase deficiency In theory, this could result in increased plasma
or glucose-galactosemalabsorption should not concentrations of bicalutamide, which
take this medicinal product. theoretically could lead to an increase in side
effects.
An increased Prothrombin Time (PT) and
International Normalised Ratio (INR)have been In vitro studies have shown that bicalutamide
reported in patients receiving bicalutamide and can displace the coumarin anticoagulant,
coumarin anticoagulants concomitantly.. Some warfarin, from its protein binding sites. There
cases have been associated with risk of bleeding. have been reports of increased Prothrombin
Close monitoring of PT/INR is advised and Time (PT) and International Normalised Ratio
anticoagulant dose adjustment should be (INR) when co-administered with bicalutamide.
considered (see sections 4.5). It is therefore recommended that if bicalutamide
is administered in patients who are already
4.5 Interaction with other medicinal products receiving coumarin anticoagulants, PT/INR
and other forms of interaction should be closely monitored.and adjustments of
anticoagulant dose considered (see sections 4.4).
 Bicalutamide 50 mg, 150mg Table ts TajPharma : U s es , Side Effects , In teractio ns , Pictures , W arnings , Bicaluta mide D os age & Rx Info | Bicalutamid e U s es , Side Effects - Anticancer, Bicalutamide : I ndications , Side Eff ects , W arnings , Bicalutamide - D rug Info rma tion - TajPha rma, Bicalu tamide d os e Taj pharmaceu ticals Bicalutamide in teractio ns , Taj Pharmaceu tical Bicalutamide con train dications , Bicaluta mide price, Bicalu tamide TajPha rma Anticancer Ta blets SmPC - TajP harma S tay connected to all upda ted on Bicalu tamide Taj Pha rmaceu ticals Taj pharmaceuticals Mu mbai. Patie nt Inf orma tion L eafle ts , SmPC.

Since androgen deprivation treatment may Organ Class y

prolong the QT interval, the concomitant use of
Blood and Very Anaemia
Bicalutamide tablets with medicinal products
lymphatic common
known to prolong the QT interval or medicinal
system
products able to induce Torsade de pointes such
disorders
as class IA (e.g. quinidine, disopyramide) or
class III (e.g. amiodarone, sotalol, dofetilide, Immune Uncommo Hypersensitivity,
ibutilide) antiarrhythmic medicinal products, system n angioedema and
methadone, moxifloxacin, antipsychotics, etc. disorders urticaria
should be carefully evaluated (see section 4.4). Metabolism Common Decreased appetite
and nutrition
Paediatric population
disorders
Interaction studies have only been performed in Psychiatric Common Decreased libido
adults. disorders depression
4.6 Fertility, pregnancy and lactation Nervous Very Dizziness
Pregnancy system common
disorders Common Somnolence
Bicalutamide is contra-indicated in females and
must not be given to pregnant women. Cardiac Common Myocardial infarction
disorders (fatal outcomes have
Breast-feeding
been reported)4,
Bicalutamide is contraindicated during breast- Cardiac failure4
feeding. Not QT prolongation (see
Fertility known sections 4.4 and 4.5)
Vascular Very Hot flush
Reversible impairment of male fertility has been disorders common
observed in animal studies (see section 5.3). A
period of subfertility or infertility should be Respiratory, Uncommo Interstitial lung
assumed in man. thoracic and n disease5 (fatal
mediastinal outcomes have been
4.7 Effects on ability to drive and use disorders reported).
machines Gastrointestin Very Abdominal pain
Bicalutamide is unlikely to impair the ability of al disorders common constipation
patients to drive or operate machinary. However, nausea
it should be noted that occasionally somnolence
may occur. Any affected patients should Common Dyspepsia
exercise caution. flatulence
Hepato- Common Hepatotoxicity,
4.8 Undesirable effects biliary jaundice,
In this section, undesirable effects are defined as disorders hypertransaminasaem
follows: very common (≥1/10); common ia1
(≥1/100, < 1/10); uncommon (≥1/1,000, <
1/100); rare (≥1/10,000, < 1/1,000); very rare (< Rare Hepatic failure2 (fatal
1/10,000); not known (cannot be estimated from outcomes have been
the available data). reported).
Skin and Common Alopecia
Table 1 Frequency of Adverse Reactions subcutaneous hirsutism/hair re-
System Frequenc Event tissue growth
 Bicalutamide 50 mg, 150mg Table ts TajPharma : U s es , Side Effects , In teractio ns , Pictures , W arnings , Bicaluta mide D os age & Rx Info | Bicalutamid e U s es , Side Effects - Anticancer, Bicalutamide : I ndications , Side Eff ects , W arnings , Bicalutamide - D rug Info rma tion - TajPha rma, Bicalu tamide d os e Taj pharmaceu ticals Bicalutamide in teractio ns , Taj Pharmaceu tical Bicalutamide con train dications , Bicaluta mide price, Bicalu tamide TajPha rma Anticancer Ta blets SmPC - TajP harma S tay connected to all upda ted on Bicalu tamide Taj Pha rmaceu ticals Taj pharmaceuticals Mu mbai. Patie nt Inf orma tion L eafle ts , SmPC.

disorders dry skin Reporting suspected adverse reactions after

pruritus rash authorisation of the medicinal product is
important. It allows continued monitoring of the
Rare Photosensitivity
benefit/risk balance of the medicinal product.
reaction
Renal and Very Haematuria 4.9 Overdose
urinary common There is no human experience of overdosage.
disorders There is no specific antidote; treatment should
be symptomatic. Dialysis is may not be helpful,
Reproductive Very Gynaecomastia and
since bicalutamide is highly protein bound and is
system and common breast tenderness 3
not recovered unchanged in the urine. General
breast Common Erectile dysfunction supportive care, including frequent monitoring
disorders
of vital signs, is indicated.
General Very Asthenia oedema
disorders and common 5. PHARMACOLOGICAL
administration Common Chest pain PROPERTIES
site conditions
Investigations Common Weight increased 5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Hormone
1. Hepatic changes are rarely severe and were antagonists and related agent,Antiandrogens
frequently transient, resolving or improving with
continued therapy or following cessation of Mechanism of action
therapy
Bicalutamide is non steroidalantiandrogen,
2. Listed as an adverse drug reaction following devoid of other endocrine activity. It binds to
review of post-marketed data. Frequency has androgen receptors without activating gene
been determined from the incidence of reported expression, and thus inhibits the androgen
adverse events of hepatic failure in patients stimulus. Regression of prostatic tumors results
receiving treatment in the open-label from this inhibition. Clinically, discontinuation
bicalutamide arm of the 150 mg EPC studies. of bicalutamide can result in antiandrogen
withdrawal syndrome in a subset of patients.
3. May be reduced by concomitant castration.
Bicalutamide is a racemate with its
4. Observed in a pharmaco-epidemiology study antiandrogenic activity being almost exclusively
of LHRH agonists and anti-androgens used in in the (R)-enantiomer.
the treatment of prostate cancer. The risk
appears to be increased when bicalutamide was 5.2 Pharmacokinetic properties
used in combination with LHRH agonists but no Absorption
increase in risk was evident when bicalutamide
was used as a monotherapy to treat prostate Bicalutamide is well absorbed following oral
cancer. administration. There is no evidence of any
clinically relevant effect of food on
5. Listed as an adverse drug reaction following bioavailability.
review of post-marketed data. Frequency has
Distribution
been determined from the incidence of reported
adverse events of interstitial pneumonia in the Bicalutamide is highly protein bound (racemate
randomised treatment period of the 150 mg EPC 96% (R)-enantiomer >99%) and extensively
studies. metabolised (via oxidation and glucuronidation):
Reporting of suspected adverse reactions Its metabolites are eliminated via the kidneys
and bile in approximately equal proportions.
 Bicalutamide 50 mg, 150mg Table ts TajPharma : U s es , Side Effects , In teractio ns , Pictures , W arnings , Bicaluta mide D os age & Rx Info | Bicalutamid e U s es , Side Effects - Anticancer, Bicalutamide : I ndications , Side Eff ects , W arnings , Bicalutamide - D rug Info rma tion - TajPha rma, Bicalu tamide d os e Taj pharmaceu ticals Bicalutamide in teractio ns , Taj Pharmaceu tical Bicalutamide con train dications , Bicaluta mide price, Bicalu tamide TajPha rma Anticancer Ta blets SmPC - TajP harma S tay connected to all upda ted on Bicalu tamide Taj Pha rmaceu ticals Taj pharmaceuticals Mu mbai. Patie nt Inf orma tion L eafle ts , SmPC.

Biotranformation dosing in a 12-month rat study. Following 12-

months of repeated dosing in dogs (at doses of
The (S)-enantiomer is rapidly cleared relative to approximately 7 times human therapeutic
the (R)-enantiomer, the latter having a plasma concentrations at the recommended human dose
elimination half-life of about 1 week.
of 50 mg), the incidence of testicular atrophy
On daily administration of Bicalutamide Tablets was the same in dosed and control dogs after a 6
50mg, the (R)-enantiomer accumulates about 10 month recovery period. In a fertility study, male
fold in plasma as a consequence of its long half- rats had an increased time to successful mating
life. immediately after 11 weeks of dosing; reversal
was observed after 7 weeks off-dose.
Steady state plasma concentrations of the (R)-
enantiomer of approximately 9 microgram/ml 6. PHARMACEUTICAL
are observed during daily administration of 50 PARTICULARS
mg doses of Bicalutamide Tablets. At steady
state the predominantly active (R)-enantiomer 6.1 List of excipients
accounts for 99% of the total circulating Core tablet:Lactose monohydrate, Sodium starch
enantiomers. glycolate,Povidone, Magnesium stearate
Elimination Coating:Hypromellose,Macrogol, Titanium
dioxide.
In a clinical study the mean concentration of R-
bicalutamide in semen of men receiving 6.2 Incompatibilities
Bicalutamide 150 mg was 4.9 microgram/ml. Not applicable
The amount of bicalutamide potentially
delivered to a female partner during intercourse 6.3 Shelf life
is low and by extrapolation possibly equates to 2 years
approximately 0.3 microgram/kg. This is below 6.4 Special precautions for storage
that required to induce changes in offspring of This medicinal product does not require any
laboratory animals. special storage conditions
Special Populations 6.5 Nature and contents of container
The pharmacokinetics of the (R)-enantiomer are Tablets are packed in Bottle/Alu-Alu blisters
unaffected by age, renal impairment or mild to Pack Size of: 7, 14, 28, 30, 50, 90, 100 or 200
moderate hepatic impairment. There is evidence tablets.
that for subjects with severe hepatic impairment,
the (R)-enantiomer is more slowly eliminated Not all pack sizes may be marketed.
from plasma. 6.6 Special precautions for disposal and other
5.3 Preclinical safety data handling
Bicalutamide is a potent antiandrogen and a Any unused medicinal product or waste material
mixed function oxidase enzyme inducer in should be disposed of in accordance with local
animals. Target organ changes, including tumour requirements.
induction, in animals, are related to these 7.Manufactured in India By:
activities. Atrophy of seminiferous tubules of the
TAJ PHARMACEUTICALS LIMITED
testes is a predicted class effect with
antiandrogens and has been observed for all at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
species examined. Reversal of testicular atrophy ATHIYAWAD, DABHEL, DAMAN- 396210
occurred 4 months after the completion of (INDIA).
dosing in a 6-month rat study. No recovery was
observed at 24 weeks after the completion of