Nilutamide
Generic: NILUTAMIDE
Basic Information
Manufacturer
ANI Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
d5740b8f-fbb3-4023-9133-9e359a9ab980
Indications & Usage
INDICATIONS AND 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, treatment with Nilutamide Tablets must begin on the same day as or on the day after surgical castration.
For maximum benefit, treatment with Nilutamide Tablets must begin on the same day as or on the day after surgical castration.
Warnings
WARNINGS Interstitial Pneumonitis Interstitial pneumonitis has been reported in 2% of patients in controlled clinical trials in patients exposed to nilutamide.
A small study in Japanese subjects showed that 8 of 47 patients (17%) developed interstitial pneumonitis.
Reports of interstitial changes including pulmonary fibrosis that led to hospitalization and death have been reported rarely post-marketing.
Symptoms included exertional dyspnea, cough, chest pain, and fever.
X-rays showed interstitial or alveolo-interstitial changes, and pulmonary function tests revealed a restrictive pattern with decreased DLco.
Most cases occurred within the first 3 months of treatment with Nilutamide Tablets, and most reversed with discontinuation of therapy.
A routine chest X-ray should be performed prior to initiating treatment with Nilutamide Tablets.
Baseline pulmonary function tests may be considered.
Patients should be instructed to report any new or worsening shortness of breath that they experience while on Nilutamide Tablets.
If symptoms occur, Nilutamide Tablets should be immediately discontinued until it can be determined if the symptoms are drug related.
Hepatitis Rare cases of death or hospitalization due to severe liver injury have been reported post-marketing in association with the use of Nilutamide Tablets.
Hepatotoxicity in these reports generally occurred within the first 3 to 4 months of treatment.
Hepatitis or marked increases in liver enzymes leading to drug discontinuation occurred in 1% of Nilutamide Tablet patients in controlled clinical trials.
Serum transaminase levels should be measured prior to starting treatment with Nilutamide Tablets, at regular intervals for the first 4 months of treatment, and periodically thereafter.
Liver function tests should also be obtained at the first sign or symptom suggestive of liver dysfunction, e.g.
nausea, vomiting, abdominal pain, fatigue, anorexia, "flu-like" symptoms, dark urine, jaundice, or right upper quadrant tenderness.
If at any time, a patient has jaundice, or their ALT rises above 2 times the upper limit of normal, Nilutamide Tablets should be immediately discontinued with close follow-up of liver function tests until resolution.
Use in Women Nilutamide Tablets have no indication for women, and should not be used in this population, particularly for non-serious or non-life threatening conditions.
Other Foreign post-marketing surveillance has revealed isolated cases of aplastic anemia in which a causal relationship with Nilutamide Tablets could not be ascertained.
A small study in Japanese subjects showed that 8 of 47 patients (17%) developed interstitial pneumonitis.
Reports of interstitial changes including pulmonary fibrosis that led to hospitalization and death have been reported rarely post-marketing.
Symptoms included exertional dyspnea, cough, chest pain, and fever.
X-rays showed interstitial or alveolo-interstitial changes, and pulmonary function tests revealed a restrictive pattern with decreased DLco.
Most cases occurred within the first 3 months of treatment with Nilutamide Tablets, and most reversed with discontinuation of therapy.
A routine chest X-ray should be performed prior to initiating treatment with Nilutamide Tablets.
Baseline pulmonary function tests may be considered.
Patients should be instructed to report any new or worsening shortness of breath that they experience while on Nilutamide Tablets.
If symptoms occur, Nilutamide Tablets should be immediately discontinued until it can be determined if the symptoms are drug related.
Hepatitis Rare cases of death or hospitalization due to severe liver injury have been reported post-marketing in association with the use of Nilutamide Tablets.
Hepatotoxicity in these reports generally occurred within the first 3 to 4 months of treatment.
Hepatitis or marked increases in liver enzymes leading to drug discontinuation occurred in 1% of Nilutamide Tablet patients in controlled clinical trials.
Serum transaminase levels should be measured prior to starting treatment with Nilutamide Tablets, at regular intervals for the first 4 months of treatment, and periodically thereafter.
Liver function tests should also be obtained at the first sign or symptom suggestive of liver dysfunction, e.g.
nausea, vomiting, abdominal pain, fatigue, anorexia, "flu-like" symptoms, dark urine, jaundice, or right upper quadrant tenderness.
If at any time, a patient has jaundice, or their ALT rises above 2 times the upper limit of normal, Nilutamide Tablets should be immediately discontinued with close follow-up of liver function tests until resolution.
Use in Women Nilutamide Tablets have no indication for women, and should not be used in this population, particularly for non-serious or non-life threatening conditions.
Other Foreign post-marketing surveillance has revealed isolated cases of aplastic anemia in which a causal relationship with Nilutamide Tablets could not be ascertained.
Adverse Reactions
ADVERSE REACTIONS Clinical Trial Experience The following adverse experiences were reported during a multicenter clinical trial comparing Nilutamide Tablets + 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 Tablets + 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 Tablets group and 81% (188/232) for the placebo group.
The following adverse experiences were reported during a multicenter clinical trial comparing Nilutamide Tablets + 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 Tablets + 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 Tablets 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 Tablets in combination with surgical castration and in seven patients (3%) receiving Nilutamide Tablets in combination with leuprolide and one patient receiving placebo in combination with leuprolide.
Overall, it has been reported in 2% of patients receiving Nilutamide Tablets.
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 Tablets 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 ANI Pharmaceuticals, Inc.
at 1-800-308-6755 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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 Tablets + 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 Tablets group and 81% (188/232) for the placebo group.
The following adverse experiences were reported during a multicenter clinical trial comparing Nilutamide Tablets + 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 Tablets + 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 Tablets 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 Tablets in combination with surgical castration and in seven patients (3%) receiving Nilutamide Tablets in combination with leuprolide and one patient receiving placebo in combination with leuprolide.
Overall, it has been reported in 2% of patients receiving Nilutamide Tablets.
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 Tablets 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 ANI Pharmaceuticals, Inc.
at 1-800-308-6755 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.