Nilutamide

INDICATIONS & USAGE Metastatic Prostate Cancer Nilutamide tablets are indicated for use in combination with surgical castration for the treatment of metastatic prostate cancer (Stage D 2 ). For maximum benefit, Nilutamide treatment must begin on the same day as or on the day after surgical castration.

DOSAGE & ADMINISTRATION The recommended dosage is 300 mg once a day for 30 days, followed thereafter by 150 mg once a day. Nilutamide tablets can be taken with or without food.

ADVERSE REACTIONS Clinical Trial Experience The following adverse experiences were reported during a multicenter clinical trial comparing Nilutamide + surgical castration versus placebo + surgical castration. The most frequently reported (greater than 5%) adverse experiences during treatment with Nilutamide tablets in combination with surgical castration are listed below. For comparison, adverse experiences seen with surgical castration and placebo are also listed. Adverse Experience Nilutamide + surgical castration (N=225) % All Placebo + surgical castration (N=232) % All Cardiovascular System Hypertension 5.3 2.6 Digestive System Nausea 9.8 6.0 Constipation 7.1 3.9 Endocrine System Hot flushes 28.4 22.4 Metabolic and Nutritional System Increased AST 8.0 3.9 Increased ALT 7.6 4.3 Nervous System Dizziness 7.1 3.4 Respiratory System Dyspnea 6.2 7.3 Special Senses Impaired adaptation to dark 12.9 1.3 Abnormal vision 6.7 1.7 Urogenital System Urinary tract infection 8.0 9.1 The overall incidence of adverse experiences was 86% (194/225) for the Nilutamide group and 81% (188/232) for the placebo group. The following adverse experiences were reported during a multicenter clinical trial comparing Nilutamide + leuprolide versus placebo + leuprolide. The most frequently reported (greater than 5%) adverse experiences during treatment with Nilutamide tablets in combination with leuprolide are listed below. For comparison, adverse experiences seen with leuprolide and placebo are also listed. Adverse Experience Nilutamide + leuprolide (N=209) % All Placebo + leuprolide (N=202) % All Body as a Whole Pain 26.8 27.7 Headache 13.9 10.4 Asthenia 19.1 20.8 Back pain 11.5 16.8 Abdominal pain 10.0 5.4 Chest pain 7.2 4.5 Flu syndrome 7.2 3.0 Fever 5.3 6.4 Cardiovascular System Hypertension 9.1 9.9 Digestive System Nausea 23.9 8.4 Constipation 19.6 16.8 Anorexia 11.0 6.4 Dyspepsia 6.7 4.5 Vomiting 5.7 4.0 Endocrine System Hot flushes 66.5 59.4 Impotence 11.0 12.9 Libido decreased 11.0 4.5 Hemic and Lymphatic System Anemia 7.2 6.4 Metabolic and Nutritional System Increased AST 12.9 13.9 Peripheral edema 12.4 17.3 Increased ALT 9.1 8.9 Musculoskeletal System Bone Pain 6.2 5.0 Nervous System Insomnia 16.3 15.8 Dizziness 10.0 11.4 Depression 8.6 7.4 Hypesthesia 5.3 2.0 Respiratory System Dyspnea 10.5 7.4 Upper respiratory infection 8.1 10.9 Pneumonia 5.3 3.5 Skin and Appendages Sweating 6.2 3.0 Body hair loss 5.7 0.5 Dry skin 5.3 2.5 Rash 5.3 4.0 Special Senses Impaired adaptation to dark 56.9 5.4 Chromatopsia 8.6 0.0 Impaired adaptation to light 7.7 1.0 Abnormal vision 6.2 4.5 Urogenital System Testicular atrophy 16.3 12.4 Gynecomastia 10.5 11.9 Urinary tract infection 8.6 21.3 Hematuria 8.1 7.9 Urinary tract disorder 7.2 10.4 Nocturia 6.7 6.4 The overall incidence of adverse experiences is 99.5% (208/209) for the Nilutamide group and 98.5% (199/202) for the placebo group. Some frequently occurring adverse experiences, for example hot flushes, impotence, and decreased libido, are known to be associated with low serum androgen levels and known to occur with medical or surgical castration alone. Notable was the higher incidence of visual disturbances (variously described as impaired adaptation to darkness, abnormal vision, and colored vision), which led to treatment discontinuation in 1% to 2% of patients. Interstitial pneumonitis occurred in one (<1%) patient receiving Nilutamide in combination with surgical castration and in seven patients (3%) receiving Nilutamide in combination with leuprolide and one patient receiving placebo in combination with leuprolide. Overall, it has been reported in 2% of patients receiving Nilutamide. This included a report of interstitial pneumonitis in 8 of 47 patients (17%) in a small study performed in Japan. In addition, the following adverse experiences were reported in 2 to 5% of patients treated with Nilutamide in combination with leuprolide or orchiectomy. Body as a Whole: Malaise (2%). Cardiovascular System: Angina (2%), heart failure (3%), syncope (2%). Digestive System : Diarrhea (2%), gastrointestinal disorder (2%), gastrointestinal hemorrhage (2%), melena (2%). Metabolic and Nutritional System: Alcohol intolerance (5%), edema (2%), weight loss (2%). Musculoskeletal System : Arthritis (2%). Nervous System: Dry mouth (2%), nervousness (2%), paresthesia (3%). Respiratory System : Cough increased (2%), interstitial lung disease (2%), lung disorder (4%), rhinitis (2%). Skin and Appendages: Pruritus (2%). Special Senses: Cataract (2%), photophobia (2%). Laboratory Values: Haptoglobin increased (2%), leukopenia (3%), alkaline phosphatase increased (3%), BUN increased (2%), creatinine increased (2%), hyperglycemia (4%). To report SUSPECTED ADVERSE REACTIONS, contact Prasco Laboratories at 1-866-525-0688 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.