Bicalutamideside effects

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. Adverse reactions that occurred in more than 10% of patients receiving bicalutamide plus an LHRH-A were: hot flashes, pain (including general, back, pelvic and abdominal), asthenia, constipation, infection, nausea, peripheral edema, dyspnea, diarrhea, hematuria, nocturia, and anemia. To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience In patients with advanced prostate cancer treated with bicalutamide in combination with an LHRH analog, the most frequent adverse reaction was hot flashes (53%). 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. Table 1 Incidence of Adverse Reactions (≥ 5% in Either Treatment Group) Regardless of Causality Body System Adverse Reaction Treatment Group Number of Patients (%) Bicalutamide Plus LHRH Analog (n=401) Flutamide Plus LHRH Analog (n=407) Body as a Whole Pain (General) 142 127 Back Pain 102 105 Asthenia 89 87 Pelvic Pain 85 70 Infection 71 57 Abdominal Pain 46 46 Chest Pain 34 34 Headache 29 27 Flu Syndrome 28 30 Cardiovascular Hot Flashes 211 217 Hypertension 34 29 Digestive Constipation 87 69 Nausea 62 58 Diarrhea 49 107 Increased Liver Enzyme Test 30 46 Dyspepsia 30 23 Flatulence 26 22 Anorexia 25 29 Vomiting 24 32 Hemic and Lymphatic Anemia 45 53 Metabolic and Nutritional Peripheral Edema 53 42 Weight Loss 30 39 Hyperglycemia 26 27 Alkaline Phosphatase Increased 22 24 Weight Gain 22 18 Musculoskeletal Bone Pain 37 43 Myasthenia 27 19 Arthritis 21 29 Pathological Fracture 17 32 Nervous System Dizziness 41 35 Paresthesia 31 40 Insomnia 27 39 Anxiety 20 9 Depression 16 33 Respiratory System Dyspnea 51 32 Cough Increased 33 24 Pharyngitis 32 23 Bronchitis 24 22 Pneumonia 18 19 Rhinitis 15 22 Skin and Appendages Rash 35 30 Sweating 25 20 Urogenital Nocturia 49 55 Hematuria 48 26 Urinary Tract Infection 35 36 Gynecomastia 36 30 Impotence 27 35 Breast Pain 23 15 Urinary Frequency 23 29 Urinary Retention 20 14 Urinary Impaired 19 15 Urinary Incontinence 15 32 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 Cardiovascular: Angina Pectoris; Congestive Heart Failure; Myocardial Infarct; Heart Arrest; Coronary Artery Disorder;

Syncope Digestive: Melena; Rectal Hemorrhage; Dry Mouth; Dysphagia; Gastrointestinal Disorder; Periodontal Abscess; Gastrointestinal Carcinoma Metabolic and Nutritional: Edema; BUN Increased; Creatinine Increased; Dehydration; Gout;

Hypercholesteremia Musculoskeletal: Myalgia;

Leg Cramps Nervous: Hypertonia; Confusion; Somnolence; Libido Decreased; Neuropathy;

Nervousness Respiratory: Lung Disorder; Asthma; Epistaxis;

Sinusitis Skin and Appendages: Dry Skin; Alopecia; Pruritus; Herpes Zoster; Skin Carcinoma;

Skin Disorder Special Senses: Cataract Specified Urogenital: 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.

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of bicalutamide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Respiratory disorders: Interstitial lung disease (some fatal) including interstitial pneumonitis and pulmonary fibrosis, most often at doses greater than 50 mg.

Hemorrhage: Increased PT/INR due to interaction between coumarin anticoagulants and bicalutamide. Serious bleeding reported. Skin and subcutaneous tissue disorders: Photosensitivity