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TEVA-BICALUTAMIDE is a brand name for Bicalutamide, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: AND CLINICAL USE .............................................................................. 3 CONTRAINDICATIONS ................................................................................................... 3 WARNINGS AND PRECAUTIONS…
Verbatim from this product's HC label. Tap a section to expand.
Recommended Dose and Dosage Adjustment TEVA-BICALUTAMIDE 50 mg in metastatic disease: The recommended dose for TEVA- BICALUTAMIDE (bicalutamide) therapy in combination with an LHRH analogue or surgical castration is one 50 mg tablet once daily with or without food.
TEVA-BICALUTAMIDE treatment should be started at the same time as treatment with an LHRH analogue or after surgical castration.
Dosing Considerations in Special Populations Renal or Hepatic Impairment:
No dosage adjustment is necessary for patients with renal or mild hepatic impairment. Increased accumulation may occur in patients with moderate to severe hepatic impairment (see WARNINGS AND PRECAUTIONS). OVERDOSAGE A single dose of bicalutamide that results in symptoms of an overdose considered to be life- threatening has not been established.
In animal studies, bicalutamide demonstrated a low potential acute toxicity. The LD50 in mice and rats was greater than 2000 mg/kg. Long-term clinical trials have been conducted with doses up to 200 mg of bicalutamide daily and these doses have been well tolerated.
There is no specific antidote; treatment of an overdose should be symptomatic. In the management of an overdose with TEVA-BICALUTAMIDE, vomiting may be induced if the patient is alert. It should be remembered that in this patient population multiple drugs may have been taken.
Dialysis is not likely to be helpful since bicalutamide is highly protein bound and is extensively metabolized. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.
ACTION AND CLINICAL PHARMACOLOGY Pharmacodynamices Bicalutamide is a non-steroidal anti-androgen, devoid of other endocrine activity. Bicalutamide competitively inhibits the action of androgens by binding to cytosol androgen receptors in target tissue.
This inhibition results in regression of prostatic tumours. Bicalutamide is a racemate and the (R)-enantiomer is primarily responsible for the anti-androgenic activity of bicalutamide. Pharmacokinetics The absorption, distribution, metabolism and excretion of bicalutamide have been investigated after administration of a single 50 mg oral dose to volunteers.
Adverse Drug Reaction Overview Bicalutamide in Metastatic Patients In patients with advanced prostate cancer, treated 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 an LHRH analogue, the most frequent adverse experiences included: hot flushes (53%), asthenia (22%), constipation (22%), nausea (14%), peripheral edema (13%), anemia (13%), haematuria (12%), abdominal pain (11%), dizziness (10%), gynecomastia (9%), rash (9%), chest pain (8%), erectile dysfunction (7%), flatulence (7%), dyspepsia (7%), decreased appetite (6%), breast tenderness (6%), weight increase (5%), cardiac failure (4%), depression (4%), dry skin (4%), alopecia (4%), pruritus (3%), somnolence (3%), myocardial infarction (3%), decreased libido (2%), hirsutism (2%), and hypersensitivity reactions (1%) including angioedema and urticaria.
Adverse event reports of abnormal liver function test results occurred in 7% of patients. These changes were frequently transient and rarely severe, resolving or improving with continued therapy or following cessation of therapy. Hepatic failure and interstitial lung disease (see WARNINGS AND PRECAUTIONS) have been observed in post-marketed data and fatal outcomes have been reported for both.
Bicalutamide, in general has been well tolerated with few withdrawals due to adverse events. 7%). After a 160 week follow-up, there were 213/401 deaths in the bicalutamide-LHRH arm and 235/407 deaths in the flutamide-LHRH arm of the trial.
There were 30 vs. 18 deaths due to adverse events in the two arms respectively and in both arms, the most common causes of death due to adverse events were attributed to the cardiovascular system (see ‘Cardiovascular’ under the ‘Clinical Trial Adverse Drug Reactions’ sub-section below).
Myocardial infarction and cardiac failure were observed in a pharmaco-epidemiology study of LHRH agonists and anti-androgens used in the treatment of prostate cancer. The risk appeared to be increased when bicalutamide was used in combination with LHRH agonists.
TEVA-BICALUTAMIDE (bicalutamide) should only be prescribed by a qualified healthcare professional who is experienced with the treatment of prostate cancer and the use of anti- androgens. Bicalutamide 150 mg/day dose should not be used (see WARNINGS & PRECAUTIONS, General).
Rare hepatic failure, including fatal outcomes (see WARNINGS & PRECAUTIONS, Hepatic). Uncommon interstitial lung disease, including fatal outcomes (see WARNINGS & PRECAUTIONS, Respiratory). General During treatment with bicalutamide, somnolence has been reported and those patients who experience this symptom should observe caution when driving or using machines.
Localized Prostate Cancer patients Bicalutamide 150 mg is NOT to be administered. 4 year median follow-up, the use of bicalutamide 150 mg as immediate therapy for the treatment of localized prostate cancer in patients otherwise undergoing watchful waiting is associated with increased mortality.
Health Canada previously assessed bicalutamide 150 mg versus castration in the locally advanced patient population and found level 1 scientific evidence (one of the 2 randomized clinical trials) of increased mortality in bicalutamide 150 mg treated patients.
Patients taking bicalutamide 50 mg per day for the treatment of metastatic prostate cancer are not affected by this new information. Anti-androgen Withdrawal Syndrome In some patients with metastatic prostate cancer, anti-androgens (steroidal and non-steroidal), may promote, rather than inhibit, the growth of prostate cancer.
A decrease in PSA and/or clinical improvement following discontinuation of anti-androgens has been reported. It is recommended that patients prescribed an anti-androgen, who have PSA progression, should have the anti- androgen discontinued immediately and be monitored for 6 - 8 weeks for a withdrawal response prior to any decision to proceed with other prostate cancer therapy.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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The results indicated that the dose was extensively absorbed and was excreted almost equally in urine (36%) and faeces (43%) over a 9 day collection period. There is no evidence of any clinically significant effect of food on bioavailability.
For management of a suspected drug overdose, contact your regional Poison Control Centre. Page 14 of 33 Steady state plasma concentrations of the (R)-enantiomer of approximately 9 mcg/mL are observed during daily administration of 50 mg doses of bicalutamide.
At steady state, the active (R)-enantiomer accounts for 99% of the circulating plasma bicalutamide concentration. 6%). On daily administration, the (R)-enantiomer accumulates about 10-fold in plasma, consistent with an elimination half-life of approximately one week.
The (S)-enantiomer is very rapidly cleared relative to the (R)-enantiomer. Bicalutamide is extensively metabolized via both oxidation and glucuronidation with approximately equal renal and biliary elimination of the metabolites.
Special Populations and Conditions Pediatrics:
The pharmacokinetics of the (R)-enantiomer are unaffected by age.
Geriatrics:
The pharmacokinetics of the (R)-enantiomer are unaffected by age.
Hepatic Insufficiency:
The pharmacokinetics of the (R)-enantiomer are unaffected by mild to moderate hepatic impairment. Patients with severe hepatic impairment eliminate the (R)- enantiomer from plasma more slowly.
Renal Insufficiency:
The pharmacokinetics of the (R)-enantiomer are unaffected by renal impairment. STORAGE AND STABILITY Store between 15 - 30°C. DOSAGE FORMS, COMPOSITION AND PACKAGING In addition to the active ingredient bicalutamide, each tablet contains the following inactive ingredients: microcrystalline cellulose, povidone, croscarmellose sodium, sodium lauryl sulfate, lactose monohydrate, colloidal silicon dioxide, magnesium stearate, polydextrose, titanium dioxide, hydroxypropyl-methylcellulose, and polyethylene glycol.
TEVA-BICALUTAMIDE 50 mg tablets are white, round, film-coated tablets debossed with “93” on one side and the other side debossed with “220". Available in unit dose blister packs of 30 tablets, and bottles of 100 and 500. 37 Structural Formula: Physiochemical Properties: Bicalutamide is a fine white to off white powder which is practically insoluble in water at 37°C (5 mg per 1000 mL), slightly soluble in chloroform and absolute ethanol, sparingly soluble in methanol, and soluble in acetone and tetrahydrofuran.
The pKa is approximately 12. The melting point range is 191-193°C. Bicalutamide is a racemate with its anti-androgen activity being predominately exhibited by the (R)- enantiomer of bicalutamide. CLINICAL TRIALS Comparative Bioavailability Study A comparative, two-way, single-dose bioavailability study was performed under fasting conditions on TEVA-BICALUTAMIDE (bicalutamide) 50 mg tablets and CASODEX® 50 mg tablets.
00) * Teva-Bicalutamide † Casodex® 50 mg Tablets manufactured by […]
Fatal outcomes of myocardial infarction have been reported. Clinical Trial Adverse Drug Reactions The following adverse experiences were reported within the same clinical trial with an incidence of ≥5%, regardless of causality. Page 9 of 33 Table 1 Incidence Of Adverse Events (≥ 5% In Either Treatment Group) Regardless Of Causality Adverse Event Treatment Group Number of Patients (%) Bicalutamide Plus LHRH Analogue (n=401) Flutamide Plus LHRH Analogue (n=407) Hot Flushes 211 (53) 217 (53) Pain (General) 142 (35) 127 (31) Back Pain 102 (25) 105 (26) Asthenia 89 (22) 87 (21) Constipation 87 (22) 69 (17) Pelvic Pain 85 (21) 70 (17) Infection 71 (18) 57 (14) Nausea 56 (14) 54 (13) Peripheral Edema 53 (13) 42 (10) Anemiaa 51 (13) 60 (15) Dyspnea 51 (13) 32 (8) Diarrhea 49 (12) 107 (26) Nocturia 49 (12) 55 (14) Hematuria 48 (12) 26 (6) Abdominal Pain 46 (11) 46 (11) Dizziness 41 (10) 35 (9) Bone Pain 37 (9) 43 (11) Gynecomastia 36 (9) 30 (8) Rash 35 (9) 30 (7) Urinary Tract Infection 35 (9) 36 (9) Chest Pain 34 (8) 34 (8) Hypertension 34 (8) 29 (7) Cough Increased 33 (8) 24 (6) Pharyngitis 32 (8) 23 (6) Paresthesia 31 (8) 40 (10) Increased Liver Enzyme Testb 30 (7) 46 (11) Weight Loss 30 (7) 39 (10) Headache 29 (7) 27 (7) Flu Syndrome 28 (7) 20 (5) Myasthenia 27 (7) 19 (5) Insomnia 27 (7) 39 (10) Erectile Dysfunction 27 (7) 35 (9) Flatulence 26 (7) 22 (5) Hyperglycemia 26 (7) 27 (7) Dyspepsia 26 (7) 23 (6) Decreased Appetite 25 (6) 29 (7) Sweating 25 (6) 20 (5) Bronchitis 24 (6) 11 (3) Page 10 of 33 Adverse Event Treatment Group Number of Patients (%) Bicalutamide Plus LHRH Analogue (n=401) Flutamide Plus LHRH Analogue (n=407) Breast Pain (tenderness) 23 (6) 15 (4) Urinary Frequency 23 (6) 29 (7) Alkaline Phosphatase Increased 22 (5) 24 (6) Weight Increased 22 (5) 18 (4) Arthritis 21 (5) 29 (7) Anxiety 20 (5) 9 (2) Urinary Retention 20 (5) 14 (3) Urinary Impaired 19 (5) 15 (4) Pneumonia 18 (4) 19 (5) Pathological Fracture 17 (4) 32 (8) Depression 16 (4) 33 (8) Vomiting 16 (4) 28 (7) Rhinitis 15 (4) 22 (5) Urinary Incontinence 15 (4) 32 (8) a Anemia includes hypochromic anemia and iron deficiency anemia.
b Abnormal liver function tests reported as adverse events. In addition, the following adverse experiences were reported by investigators within the same clinical trial (as possible adverse drug reactions in the opinion of investigating clinicians) with a frequency of less than 5%, during treatment with bicalutamide 50 mg plus an LHRH analogue.
These experiences are not necessarily considered as causally related to drug treatment.
Cardiovascular:
In the pivotal trial of 813 patients comparing bicalutamide 50 mg once daily with flutamide 250 mg three times a day, each in combination with an LHRH analogue, an imbalance of deaths related to cardiovascular adverse events was noted (bicalutamide-LHRH therapy: 18 deaths; flutamide-LHRH therapy: 9 deaths) however, there is difficulty in interpreting this imbalance as the exposure was longer on the bicalutamide-LHRH arm by a mean of 13 weeks.
Other cardiovascular-related experiences reported include angina pectoris, congestive heart failure, myocardial infarction, heart arrest, coronary artery disorder, syncope, atrial fibrillation, cerebrovascular accident, deep thrombophlebitis, arrhythmia, bradycardia, cerebral ischemia, hemorrhage.
Central Nervous System: hypertonia, confusion, somnolence, decreased libido, neuropathy, nervousness Endocrine System: diabetes mellitus Gastrointestinal: melena, rectal hemorrhage, dry mouth, dysphagia, gastrointestinal Page 11 of 33 disorder, periodontal abscess, gastrointestinal carcinoma, rectal disorder, intestinal obstruction, gastritis Hematological: ecchymosis, […]
Cardiovascular TEVA-BICALUTAMIDE is indicated for use in combination with either an LHRH analogue or surgical castration. Combined androgen blockade with an anti-androgen plus LHRH analogue or surgical castration increases risk of cardiovascular disease (heart attack, cardiac failure, sudden cardiac death) and adversely affects independent cardiovascular risk factors (serum lipoproteins, Page 5 of 33 insulin sensitivity and obesity).
Physicians should carefully consider whether the benefits of combined androgen blockade outweigh the potential cardiovascular risk. Assessment of cardiovascular risk factors, monitoring for signs and symptoms suggestive of development of cardiovascular disease, and management according to local clinical practice and guidelines should be considered.
Effect on QT/QTc interval TEVA-BICALUTAMIDE is indicated for use in combination with either an LHRH analogue or surgical castration. Combined androgen blockade with an anti-androgen plus LHRH analogue or surgical castration has the potential to prolong QT/QTc interval on ECG.
g. g. g. flecainide, propafenone) antiarrhythmic medications (See DRUG INTERACTIONS), physicians should assess the benefit risk ratio, including the potential for Torsade de Pointes prior to initiating TEVA- BICALUTAMIDE. Endocrine and Metabolism A reduction in glucose tolerance and/or glycated hemoglobin (HbAlc) has been observed in males receiving bicalutamide in combination with LHRH analogues.
This may manifest as diabetes or loss of glycemic control in those with pre-existing diabetes. Consideration should therefore be given to monitoring blood glucose and/or glycated hemoglobin (HbAlc) in patients receiving bicalutamide in combination with LHRH analogues.
Gynaecomastia, Breast Pain Gynaecomastia has been reported in patients receiving bicalutamide. For metastatic (M1) patients receiving bicalutamide 50 mg, concomitant surgical or medical castration may reduce the effects of gynaecomastia.
Hematologic Anemia is a known physiologic consequence of testosterone suppression. Assessment of anemia risk and management according to local clinical practice and guidelines should be considered. There may be an increased risk of hemorrhage in patients taking coumarin anticoagulants that are started on bicalutamide.
(see ADVERSE REACTIONS and DRUG INTERACTIONS). Hepatic Bicalutamide is extensively metabolized in the liver. Data suggests that the elimination of bicalutamide may be slower in subjects with severe hepatic impairment and this could lead to increased accumulation of bicalutamide.
Therefore, TEVA-BICALUTAMIDE should be used with caution in patients with moderate to severe hepatic impairment. Hepatotoxicity including rare hepatic failure has been observed with bicalutamide, and fatal outcomes have been reported.
Bicalutamide therapy should be discontinued if changes are severe Page 6 of 33 (also see Post-Market Adverse Drug Reactions). Musculoskeletal Changes in Bone Density TEVA-BICALUTAMIDE is indicated for use in combination with either an LHRH analogue or surgical castration.
Decreased bone mineral density can be anticipated with long term combined androgen blockade with an anti-androgen plus LHRH analogue or surgical castration. Combined androgen blockade is associated with increased risks of osteoporosis and skeletal bone fractures.
The risk of skeletal fracture increases with the duration of combined androgen blockade. Assessment of osteoporosis risk and management according to clinical practice and guidelines should be considered. In patients with significant risk factors for decreased bone mineral content and/or bone mass […]