NDC 66993-212 Nilutamide

Nilutamide

NDC Product Code 66993-212

NDC CODE: 66993-212

Proprietary Name: Nilutamide What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Nilutamide What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This medication is used to treat men with prostate cancer, and is used after surgery (removal of the testicles) or with other medications. Nilutamide belongs to a class of drugs known as anti-androgens (anti-testosterone). Testosterone, a natural hormone, helps prostate cancer to grow and spread. Nilutamide works by blocking the effects of testosterone, thereby slowing the growth and spread of prostate cancer.

Product Characteristics

Color(s):
WHITE (C48325)
Shape: ROUND (C48348)
Size(s):
10 MM
Imprint(s):
168D
Score: 1

NDC Code Structure

  • 66993 - Prasco Laboratories

NDC 66993-212-38

Package Description: 3 BLISTER PACK in 1 CARTON > 10 TABLET in 1 BLISTER PACK

NDC Product Information

Nilutamide with NDC 66993-212 is a a human prescription drug product labeled by Prasco Laboratories. The generic name of Nilutamide is nilutamide. The product's dosage form is tablet and is administered via oral form.

Labeler Name: Prasco Laboratories

Dosage Form: Tablet - A solid dosage form containing medicinal substances with or without suitable diluents.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Nilutamide Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • NILUTAMIDE 150 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • STARCH, CORN (UNII: O8232NY3SJ)
  • LACTOSE (UNII: J2B2A4N98G)
  • DOCUSATE SODIUM (UNII: F05Q2T2JA0)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • TALC (UNII: 7SEV7J4R1U)
  • POVIDONE (UNII: FZ989GH94E)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.
  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Androgen Receptor Antagonists - [MoA] (Mechanism of Action)
  • Androgen Receptor Inhibitor - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Prasco Laboratories
Labeler Code: 66993
FDA Application Number: NDA020169 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA AUTHORIZED GENERIC - A product marketed as a “generic” drug under an approved New Drug Application (NDA), rather than an Abbreviated New Drug Application (ANDA),. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 11-22-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Information for Patients

Nilutamide

Nilutamide is pronounced as (nye loo' ta mide)

Why is nilutamide medication prescribed?
Nilutamide is used after surgery to treat prostate cancer. Nilutamide is in a class of medications called antiandrogens. It works by blocking the effect of androgen (a ma...
[Read More]

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Nilutamide Product Label Images

Nilutamide Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

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 C12H10F3N3O4. 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.

Mechanism Of Action

Prostate cancer is known to be androgen sensitive and responds to androgen ablation. In animal studies, nilutamide has demonstrated antiandrogenic activity without other hormonal (estrogen, progesterone, mineralocorticoid, and glucocorticoid) effects. In vitro, nilutamide blocks the effects of testosterone at the androgen receptor level. In vivo, nilutamide interacts with the androgen receptor and prevents the normal androgenic response.

Absorption:

Analysis of blood, urine, and feces samples following a single oral 150 mg dose of [14C]-nilutamide in patients with metastatic prostate cancer showed that the drug is rapidly and completely absorbed and that it yields high and persistent plasma concentrations.

Distribution:

After absorption of the drug, there is a detectable distribution phase. There is moderate binding of the drug to plasma proteins and low binding to erythrocytes. The binding is nonsaturable except in the case of alpha-1-glycoprotein, which makes a minor contribution to the total concentration of proteins in the plasma. The results of binding studies do not indicate any effects that would cause nonlinear pharmacokinetics.

Metabolism:

The results of a human metabolism study using 14C-radiolabelled tablets show that nilutamide is extensively metabolized and less than 2% of the drug is excreted unchanged in urine after 5 days. Five metabolites have been isolated from human urine. Two metabolites display an asymmetric center, due to oxidation of a methyl group, resulting in the formation of D- and L-isomers. One of the metabolites was shown, in vitro, to possess 25 to 50% of the pharmacological activity of the parent drug, and the D-isomer of the active metabolite showed equal or greater potency compared to the L-isomer. However, the pharmacokinetics and the pharmacodynamics of the metabolites have not been fully investigated.

Elimination:

The majority (62%) of orally administered [14C]-nilutamide is eliminated in the urine during the first 120 hours after a single 150-mg dose. Fecal elimination is negligible, ranging from 1.4% to 7% of the dose after 4 to 5 days. Excretion of radioactivity in urine likely continues beyond 5 days. The mean elimination half-life of nilutamide determined in studies in which subjects received a single dose of 100-300 mg ranged from 38.0 to 59.1 hours with most values between 41 and 49 hours. The elimination of at least one metabolite is generally longer than that of unchanged nilutamide (59-126 hours). During multiple dosing of 150 mg nilutamide (given as 3 X 50 mg) twice a day, steady state was reached within 2 to 4 weeks for most patients, and mean steady state AUC0-12 was 110% higher than the AUC0-∞ obtained from the first 150 mg dose. These data and in vitro metabolism data suggest that, upon multiple dosing, metabolic enzyme inhibition may occur for this drug.

Clinical Studies

Nilutamide through its antiandrogenic activity can complement surgical castration, which suppresses only testicular androgens. The effects of the combined therapy were studied in patients with previously untreated metastatic prostate cancer. In a double-blind, randomized, multicenter study that enrolled 457 patients (225 treated with orchiectomy and nilutamide, 232 treated with orchiectomy and placebo), the nilutamide group showed a statistically significant benefit in time to progression and time to death. The results are summarized below.    NILUTAMIDE   PLACEBO Median Survival (months)          27.3         23.6Progression-Free Survival (months)         21.1        14.9Complete or Partial Regression         41%         24%Improvement in Bone Pain         54%         37%

Indications & Usage

Metastatic Prostate Cancer Nilutamide tablets are indicated for use in combination with surgical castration for the treatment of metastatic prostate cancer (Stage D2). For maximum benefit, Nilutamide treatment must begin on the same day as or on the day after surgical castration.

Contraindications

Nilutamide tablets are contraindicated: • in patients with severe hepatic impairment (baseline hepatic enzymes should be evaluated prior to treatment) • in patients with severe respiratory insufficiency • in patients with hypersensitivity to nilutamide or any component of this preparation.

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.

General

Antiandrogen Withdrawal SyndromePatients whose disease progresses while being treated with an antiandrogen may experience clinical improvement with discontinuation of the antiandrogen.

Information For Patients

Patients should be informed that Nilutamide tablets should be started on the day of or on the day after, surgical castration. They should also be informed that they should not interrupt their dosing of Nilutamide or stop taking this medication without consulting their physician. Because of the possibility of interstitial pneumonitis, patients should also be told to report immediately any dyspnea or aggravation of pre-existing dyspnea. Because of the possibility of hepatitis, patients should be told to consult with their physician should nausea, vomiting, abdominal pain or jaundice occur. Because of the possibility of an intolerance to alcohol (facial flushes, malaise, hypotension) following ingestion of Nilutamide, it is recommended that intake of alcoholic beverages be avoided by patients who experience this reaction. This effect has been reported in about 5% of patients treated with Nilutamide. In clinical trials, 13% to 57% of patients receiving Nilutamide reported a delay in adaptation to dark, ranging from seconds to a few minutes, when passing from a lighted area to a dark area. This effect sometimes does not abate as drug treatment is continued. Patients who experience this effect should be cautioned about driving at night or through tunnels. This effect can be alleviated by the wearing of tinted glasses.

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.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Administration of nilutamide to rats for 18 months at doses of 0, 5, 15 or 45 mg/kg/day produced benign Leydig cell tumors in 35% of the high-dose male rats (AUC exposures in high-dose rats were approximately 1 - 2 times human AUC exposures with therapeutic doses). The increased incidence of Leydig cell tumors is secondary to elevated luteinizing hormone (LH) concentrations resulting from loss of feedback inhibition at the pituitary. Elevated LH and testosterone concentrations are not observed in castrated men receiving Nilutamide. Nilutamide had no effect on the incidence, size or time of onset of any spontaneous tumor in rats. Nilutamide displayed no mutagenic effects in a variety of in vitro and in vivo tests (Ames test, mouse micronucleus test, and two chromosomal aberration tests). In reproduction studies in rats, nilutamide had no effect on the reproductive function of males and females, and no lethal, teratogenic or growth-suppressive effects on fetuses were found. The maximal dose at which nilutamide did not affect reproductive function in either sex or have an effect on fetuses was estimated to be 45 mg/kg orally (AUC exposures in rats approximately 1-2 times human therapeutic AUC exposures).

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.

Pediatric Use

Safety and effectiveness in pediatric patients have not been determined.

Animal Pharmacology And Toxicology

Administration of Nilutamide to beagle dogs resulted in drug-related deaths at dose levels that produce AUC exposures in dogs much lower than the AUC exposures of men receiving the therapeutic doses of 150 and 300 mg/day. Nilutamide-induced toxicity in dogs was cumulative with progressively lower doses producing death when given for longer durations. Nilutamide given to dogs at 60 mg/kg/day (1-2 times human AUC exposure) for 1 month produced 100% mortality. Administration of 20 and 30 mg/kg/day nilutamide (1/2-1 times human AUC exposure) for 6 months resulted in 20% and 70% mortality in treated dogs. Administration to dogs of 3, 6, and 12 mg/kg/day nilutamide (1/10-1/2 human AUC exposure) for 1 year resulted in 8%, 33%,and 50% mortality, respectively. A “no-effect level” for nilutamide-induced mortality in dogs was not identified. Pathology data from the one-year oral toxicity study suggest that the deaths in dogs were secondary to liver toxicity. Marked-to-massive hepatocellular swelling and vacuolization were observed in affected dogs. Liver toxicity in dogs was not consistently associated with elevations of liver enzymes. Administration of nilutamide to rats at a dose level of 45 mg/kg/day (AUC exposure in rats 1-2 times human therapeutic AUC exposures) for 18 months increased the incidence of lung pathology (granulomatous inflammation and chronic alveolitis). The hepatic and pulmonary adverse effects observed in nilutamide-treated animals and men are similar to effects observed with another nitroaromatic compound, nitrofurantoin. Nilutamide and nitrofurantoin are both metabolized in vitro to nitroanion free-radicals by microsomal NADPH-cytochrome P450 reductase in the lungs and liver of rats and humans.

Adverse Reactions

Clinical Trial ExperienceThe 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 ExperienceNilutamide + surgical castration (N=225) % AllPlacebo + surgical castration (N=232) % AllCardiovascular System    Hypertension5.3 2.6Digestive System    Nausea9.86.0    Constipation7.1 3.9 Endocrine System     Hot flushes28.422.4Metabolic and Nutritional System    Increased AST8.03.9    Increased ALT7.64.3Nervous System    Dizziness7.13.4Respiratory System    Dyspnea6.27.3Special Senses    Impaired adaptation to dark12.91.3    Abnormal vision6.71.7Urogenital System    Urinary tract infection8.09.1The 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 ExperienceNilutamide + leuprolide (N=209) % AllPlacebo + leuprolide (N=202) % AllBody as a Whole        Pain26.827.7        Headache13.910.4        Asthenia19.120.8        Back pain11.516.8        Abdominal pain10.05.4        Chest pain7.24.5        Flu syndrome7.23.0        Fever5.36.4Cardiovascular System        Hypertension9.19.9Digestive System        Nausea23.98.4        Constipation19.616.8        Anorexia11.06.4        Dyspepsia6.74.5        Vomiting5.74.0Endocrine System        Hot flushes66.559.4        Impotence11.012.9        Libido decreased11.04.5Hemic and Lymphatic System        Anemia7.26.4Metabolic and Nutritional System        Increased AST12.913.9        Peripheral edema12.417.3        Increased ALT9.18.9Musculoskeletal System        Bone Pain6.25.0Nervous System        Insomnia16.315.8        Dizziness10.011.4        Depression8.67.4        Hypesthesia5.32.0Respiratory System        Dyspnea10.57.4        Upper respiratory infection8.110.9        Pneumonia5.33.5Skin and Appendages        Sweating6.23.0        Body hair loss5.70.5        Dry skin5.32.5        Rash5.34.0Special Senses        Impaired adaptation to dark56.95.4        Chromatopsia8.60.0        Impaired adaptation to light7.71.0        Abnormal vision6.24.5Urogenital System        Testicular atrophy16.312.4        Gynecomastia10.511.9        Urinary tract infection8.621.3        Hematuria8.17.9        Urinary tract disorder7.210.4        Nocturia6.76.4The 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.

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.

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.

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 02/2019Distributed by:Prasco LaboratoriesMason, OH 45040 USA©2019 Prasco LaboratoriesAll rights reserved.

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