ADVERSE REACTIONS
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.
Clinical Trials Experience
In patients with advanced prostate cancer treated with Bicalutamide Tablets, USP in combination with an LHRH analog, the most frequent adverse reaction was hot flashes (53%).
In the multicenter, double-blind, controlled clinical trial comparing Bicalutamide Tablets, USP 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 Tablets, USP Plus LHRH Analog (n=401) |
Flutamide Plus LHRH Analog (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) |
Cardiovascular
|
Hot Flashes |
211 (53) |
217 (53) |
Hypertension |
34 (8) |
29 (7) |
Digestive
|
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) |
Musculoskeletal
|
Bone Pain |
37 (9) |
43 (11) |
Myasthenia |
27 (7) |
19 (5) |
Arthritis |
21 (5) |
29 (7) |
Pathological Fracture |
17 (4) |
32 (8) |
Nervous System
|
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) |
Respiratory System
|
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) |
Urogenital
|
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 Tablets, USP-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 Tablets, USP-LHRH analog treated and flutamide-LHRH analog treated patients.
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of Bicalutamide Tablets, USP. 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.
Uncommon cases of hypersensitivity reactions, including angioneurotic edema and urticaria have been seen [see Contraindications]. Cases of interstitial lung disease (some fatal), including interstitial pneumonitis and pulmonary fibrosis, have been reported with Bicalutamide Tablets, USP. Interstitial lung disease has been reported most often at doses greater than 50 mg. A few cases of fatal hepatic failure have been reported.
Reduction in glucose tolerance, manifesting as diabetes or a loss of glycemic control in those with pre-existing diabetes, has been reported during treatment with LHRH agonists.
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