Nilutamide
FDA Drug Information • Also known as: Nilandron, Nilutamide
- Brand Names
- Nilandron, Nilutamide
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
⚠ Boxed Warning (Black Box)
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, and most reversed with discontinuation of therapy. A routine chest X-ray should be performed prior to initiating treatment with Nilutamide. 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. If symptoms occur, Nilutamide should be immediately discontinued until it can be determined if the symptoms are drug related.
Description
DESCRIPTION Nilutamide tablets contain nilutamide, a nonsteroidal, orally active antiandrogen having the chemical name 5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]-2,4-imidazolidinedione with the following structural formula: Nilutamide is a microcrystalline, white to practically white powder with a molecular weight of 317.25. Its molecular formula is C 12 H 10 F 3 N 3 O 4 . It is freely soluble in ethyl acetate, acetone, chloroform, ethyl alcohol, dichloromethane, and methanol. It is slightly soluble in water [<0.1% W/V at 25°C (77°F)]. It melts between 153°C and 156°C (307.4°F and 312.8°F). Each Nilutamide tablet contains 150 mg of nilutamide. Other ingredients in Nilutamide tablets are corn starch, lactose, povidone, docusate sodium, magnesium stearate, and talc. nilutamide-01.jpg
What Is Nilutamide Used For?
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 and Administration
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.
Side Effects (Adverse Reactions)
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:...
Warnings and Precautions
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, and most reversed with discontinuation of therapy. A routine chest X-ray should be performed prior to initiating treatment with Nilutamide. 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. If symptoms occur, Nilutamide 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. 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 patients in controlled clinical trials. Serum transaminase levels should be measured prior to starting treatment with Nilutamide, 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 should be immediately discontinued with close followup of liver function tests until resolution. Use in Women Nilutamide has no indication for women, and should not be used in this population, particularly for non-serious or non-life threatening conditions. Other Foreign postmarketing surveillance has revealed isolated cases of aplastic anemia in which a causal relationship with Nilutamide could not be ascertained.
Drug Interactions
Drug Interactions In vitro, nilutamide has been shown to inhibit the activity of liver cytochrome P-450 isoenzymes and, therefore, may reduce the metabolism of compounds requiring these systems. Consequently, drugs with a low therapeutic margin, such as vitamin K antagonists, phenytoin, and theophylline, could have a delayed elimination and increases in their serum half-life leading to a toxic level. The dosage of these drugs or others with a similar metabolism may need to be modified if they are administered concomitantly with nilutamide. For example, when vitamin K antagonists are administered concomitantly with nilutamide, prothrombin time should be carefully monitored and, if necessary, the dosage of vitamin K antagonists should be reduced.
Contraindications
CONTRAINDICATIONS Nilutamide tablets are contraindicated:
Pregnancy and Breastfeeding
Pregnancy Animal reproduction studies have not been conducted with nilutamide. It is also not known whether nilutamide can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Nilutamide should be given to a pregnant woman only if clearly needed.
Overdosage
OVERDOSAGE One case of massive overdosage has been published. A 79-year-old man attempted suicide by ingesting 13 g of nilutamide (i.e., 43 times the maximum recommended dose). Despite immediate gastric lavage and oral administration of activated charcoal, plasma nilutamide levels peaked at 6 times the normal range 2 hours after ingestion. There were no clinical signs or symptoms or changes in parameters such as transaminases or chest X-ray. Maintenance treatment (150 mg/day) was resumed 30 days later. In repeated-dose tolerance studies, doses of 600 mg/day and 900 mg/day were administered to 9 and 4 patients, respectively. The ingestion of these doses was associated with gastrointestinal disorders, including nausea and vomiting, malaise, headache, and dizziness. In addition, a transient elevation in hepatic enzyme levels was noted in one patient. Since nilutamide is protein bound, dialysis may not be useful as treatment for overdose. As in the management of overdosage with any drug, it should be borne in mind that multiple agents may have been taken. If vomiting does not occur spontaneously, it should be induced if the patient is alert. General supportive care, including frequent monitoring of the vital signs and close observation of the patient, is indicated.
How Supplied
HOW SUPPLIED Nilutamide 150 mg tablets are supplied in boxes of 30 tablets. Each box contains 3 child-resistant, PVC, aluminum foil-backed blisters of 10 tablets (NDC 66993-212-38). Each white, biconvex, cylindrical (10 mm in diameter) tablet has a triangular logo on one side and an internal reference number (168D) on the other. Store at 25°C (77°F); excursions permitted between 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from light. Keep out of reach of children. Revised 02/2019 Distributed by: Prasco Laboratories Mason, OH 45040 USA ©2019 Prasco Laboratories All rights reserved.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.