BICALUTAMIDE — bicalutamide tablet, film coated
Zydus Pharmaceuticals (USA) Inc.
Bicalutamide tablets 50 mg daily is indicated for use in combination therapy with a luteinizing hormone-releasing hormone (LHRH) analog for the treatment of Stage D2 metastatic carcinoma of the prostate.
Bicalutamide tablets 150 mg daily is not approved for use alone or with other treatments [see Clinical Studies (14.2)].
The recommended dose for bicalutamide tablets therapy in combination with an LHRH analog is one 50 mg tablet once daily (morning or evening), with or without food. It is recommended that bicalutamide tablets be taken at the same time each day. Treatment with bicalutamide tablets should be started at the same time as treatment with an LHRH analog.If a dose of Bicalutamide Tablet is missed, take the next dose at the scheduled time. Do not take the missed dose and do not double the next dose.
No dosage adjustment is necessary for patients with renal impairment [see Use in Specific Populations (8.7)].
No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. In patients with severe liver impairment (n=4), although there was a 76% increase in the half-life (5.9 and 10.4 days for normal and impaired patients, respectively) of the active enantiomer of bicalutamide, no dosage adjustment is necessary [see Use in Specific Populations (8.6)].
Bicalutamide is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or any of the tablet’s components. Hypersensitivity reactions including angioneurotic edema and urticaria have been reported.
Bicalutamide has no indication for women, and should not be used in this population.
Bicalutamide can cause fetal harm when administered to a pregnant woman. [see Use in Specific Populations (8.1)].
Cases of death or hospitalization due to severe liver injury (hepatic failure) have been reported post-marketing in association with the use of bicalutamide. Hepatotoxicity in these reports generally occurred within the first three to four months of treatment. Hepatitis or marked increases in liver enzymes leading to drug discontinuation occurred in approximately 1% of bicalutamide patients in controlled clinical trials.
Serum transaminase levels should be measured prior to starting treatment with bicalutamide, at regular intervals for the first four months of treatment, and periodically thereafter. If clinical symptoms or signs suggestive of liver dysfunction occur (e.g., nausea, vomiting, abdominal pain, fatigue, anorexia, “flu-like” symptoms, dark urine, jaundice, or right upper quadrant tenderness), the serum transaminases, in particular the serum ALT, should be measured immediately. If at any time a patient has jaundice, or their ALT rises above two times the upper limit of normal, bicalutamide should be immediately discontinued with close follow-up of liver function.
In the postmarketing setting, there have been reports of excessive prolongation of the prothrombin time (PT) and International Normalized Ratio (INR) days to weeks after the introduction of bicalutamide in patients who were previously stable on coumarin anticoagulants. Some patients had serious bleeding including intracranial, retroperitoneal, and gastrointestinal requiring blood transfusion and/or administration of vitamin K. Closely monitor the PT/INR, and adjust the anticoagulant dose as needed [see Drug Interactions (7) and Adverse Reactions (6.2)].
A reduction in glucose tolerance has been observed in males receiving LHRH agonists. This may manifest as diabetes or loss of glycemic control in those with preexisting diabetes. Consideration should therefore be given to monitoring blood glucose in patients receiving bicalutamide in combination with LHRH agonists.
Regular assessments of serum Prostate Specific Antigen (PSA) may be helpful in monitoring the patient’s response. If PSA levels rise during bicalutamide therapy, the patient should be evaluated for clinical progression. For patients who have objective progression of disease together with an elevated PSA, a treatment-free period of antiandrogen, while continuing the LHRH analog, may be considered.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the multi-center, 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 analog, the following adverse reactions with an incidence of 5% or greater, regardless of causality, have been reported.
|Body System Adverse Reaction||Treatment Group|
|Number of Patients (%)|
|Bicalutamide Plus LHRH Analogue (n=401)||Flutamide Plus LHRH Analogue (n=407)|
|Body as a Whole|
|Pain (General)||142 (35)||127 (31)|
|Back Pain||102 (25)||105 (26)|
|Asthenia||89 (22)||87 (21)|
|Pelvic Pain||85 (21)||70 (17)|
|Infection||71 (18)||57 (14)|
|Abdominal Pain||46 (11)||46 (11)|
|Chest Pain||34 (8)||34 (8)|
|Headache||29 (7)||27 (7)|
|Flu Syndrome||28 (7)||30 (7)|
|Hot Flashes||211 (53)||217 (53)|
|Hypertension||34 (8)||29 (7)|
|Constipation||87 (22)||69 (17)|
|Nausea||62 (15)||58 (14)|
|Diarrhea||49 (12)||107 (26)|
|Increased Liver Enzyme Test||30 (7)||46 (11)|
|Dyspepsia||30 (7)||23 (6)|
|Flatulence||26 (6)||22 (5)|
|Anorexia||25 (6)||29 (7)|
|Vomiting||24 (6)||32 (8)|
|Hemic and Lymphatic|
|Anemia||45 (11)||53 (13)|
|Metabolic and Nutritional|
|Peripheral Edema||53 (13)||42 (10)|
|Weight Loss||30 (7)||39 (10)|
|Hyperglycemia||26 (6)||27 (7)|
|Alkaline Phosphatase Increased||22 (5)||24 (6)|
|Weight Gain||22 (5)||18 (4)|
|Bone Pain||37 (9)||43 (11)|
|Myasthenia||27 (7)||19 (5)|
|Arthritis||21 (5)||29 (7)|
|Pathological Fracture||17 (4)||32 (8)|
|Dizziness||41 (10)||35 (9)|
|Paresthesia||31 (8)||40 (10)|
|Insomnia||27 (7)||39 (10)|
|Anxiety||20 (5)||9 (2)|
|Depression||16 (4)||33 (8)|
|Dyspnea||51 (13)||32 (8)|
|Cough Increased||33 (8)||24 (6)|
|Pharyngitis||32 (8)||23 (6)|
|Bronchitis||24 (6)||22 (3)|
|Pneumonia||18 (4)||19 (5)|
|Rhinitis||15 (4)||22 (5)|
|Skin and Appendages|
|Rash||35 (9)||30 (7)|
|Sweating||25 (6)||20 (5)|
|Nocturia||49 (12)||55 (14)|
|Hematuria||48 (12)||26 (6)|
|Urinary Tract Infection||35 (9)||36 (9)|
|Gynecomastia||36 (9)||30 (7)|
|Impotence||27 (7)||35 (9)|
|Breast Pain||23 (6)||15 (4)|
|Urinary Frequency||23 (6)||29 (7)|
|Urinary Retention||20 (5)||14 (3)|
|Urinary Impaired||19 (5)||15 (4)|
|Urinary Incontinence||15 (4)||32 (8)|
Other adverse reactions (greater than or equal to 2%, but less than 5%) reported in the bicalutamide-LHRH analog treatment group are listed below by body system and are in order of decreasing frequency within each body system regardless of causality.
Body as a Whole:
Neoplasm; Neck Pain; Fever; Chills; Sepsis; Hernia; Cyst
Angina Pectoris; Congestive Heart Failure; Myocardial Infarct; Heart Arrest; Coronary Artery Disorder; Syncope
Melena; Rectal Hemorrhage; Dry Mouth; Dysphagia; Gastrointestinal Disorder; Periodontal Abscess; Gastrointestinal Carcinoma
Metabolic and Nutritional:
Edema; BUN Increased; Creatinine Increased; Dehydration; Gout; Hypercholesterolemia
Myalgia; Leg Cramps
Hypertonia; Confusion; Somnolence; Libido Decreased; Neuropathy; Nervousness
Lung Disorder; Asthma; Epistaxis; Sinusitis
Skin and Appendages:
Dry Skin; Alopecia; Pruritus; Herpes Zoster; Skin Carcinoma; Skin Disorder
Dysuria; Urinary Urgency; Hydronephrosis; Urinary Tract Disorder
Abnormal Laboratory Test Values
Laboratory abnormalities including: elevated AST, ALT, bilirubin, BUN, and creatinine; and decreased hemoglobin and white cell count, have been reported in both bicalutamide-LHRH analog treated and flutamide-LHRH analog treated patients.
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