NDC 60429-272 Flutamide

Flutamide

NDC Product Code 60429-272

NDC CODE: 60429-272

Proprietary Name: Flutamide 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: Flutamide 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. Flutamide belongs to a class of drugs known as anti-androgens (anti-testosterone). Testosterone, a natural hormone, helps prostate cancer to grow and spread. Flutamide works by blocking the effects of testosterone, thereby slowing the growth and spread of prostate cancer.

Product Characteristics

Color(s):
BROWN (C48332 - BEIGE)
Shape: CAPSULE (C48336)
Size(s):
22 MM
Imprint(s):
93;7120
Score: 1

NDC Code Structure

  • 60429 - Golden State Medical Supply, Inc.

NDC 60429-272-18

Package Description: 180 CAPSULE in 1 BOTTLE

NDC Product Information

Flutamide with NDC 60429-272 is a a human prescription drug product labeled by Golden State Medical Supply, Inc.. The generic name of Flutamide is flutamide. The product's dosage form is capsule and is administered via oral form.

Labeler Name: Golden State Medical Supply, Inc.

Dosage Form: Capsule - A solid oral dosage form consisting of a shell and a filling. The shell is composed of a single sealed enclosure, or two halves that fit together and which are sometimes sealed with a band. Capsule shells may be made from gelatin, starch, or cellulose, or other suitable materials, may be soft or hard, and are filled with solid or liquid ingredients that can be poured or squeezed.

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.

Flutamide 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.

  • FLUTAMIDE 125 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 MONOHYDRATE (UNII: EWQ57Q8I5X)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • GELATIN, UNSPECIFIED (UNII: 2G86QN327L)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • FERRIC OXIDE RED (UNII: 1K09F3G675)
  • FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
  • SHELLAC (UNII: 46N107B71O)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • BUTYL ALCOHOL (UNII: 8PJ61P6TS3)
  • FD&C BLUE NO. 2 (UNII: L06K8R7DQK)
  • FD&C RED NO. 40 (UNII: WZB9127XOA)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)

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.

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: Golden State Medical Supply, Inc.
Labeler Code: 60429
FDA Application Number: ANDA075298 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: ANDA - A product marketed under an approved Abbreviated New Drug Application. 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: 09-18-2001 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: 12-31-2021 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 - NO 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 ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Information for Patients

Flutamide

Flutamide is pronounced as (floo' ta mide)

Why is flutamide medication prescribed?
Flutamide is used together with a luteinizing hormone-releasing hormone agonist (LHRH; a type of hormonal injection such as leuprolide [Lupron, Eligard], goserelin [Zolad...
[Read More]

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Flutamide 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

Flutamide capsules contain flutamide, an acetanilid, nonsteroidal, orally active antiandrogen having the chemical name, α,α,α-trifluoro-2-methyl-4'-nitrom-propionotoluidide.Each capsule contains 125 mg flutamide. The compound is a buff to yellow powder with a molecular weight of 276.22 and the following structural formula:C11H11F3N2O3In addition, each capsule contains the following inactive ingredients: corn starch, lactose monohydrate, magnesium stearate, povidone, and sodium lauryl sulfate. Gelatin capsule shells may contain gelatin, silicon dioxide, sodium lauryl sulfate, titanium dioxide, FDA/E172 Red Iron Oxide, FDA/E172 Yellow Iron Oxide, and black ink containing pharmaceutical glaze (modified) in SD-45, synthetic black iron oxide, N-butyl alcohol, SDA-3A alcohol, FD&C Blue No.2 Aluminum Lake, FD&C Red No.40 Aluminum Lake, FD&C Blue No.1 Aluminum Lake, and D&C Yellow No.10 Aluminum Lake.

General

In animal studies, flutamide demonstrates potent antiandrogenic effects. It exerts its antiandrogenic action by inhibiting androgen uptake and/or by inhibiting nuclear binding of androgen in target tissues or both. Prostatic carcinoma is known to be androgen-sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen, e.g., castration. Elevations of plasma testosterone and estradiol levels have been noted following flutamide administration.

In clinical trials, gynecomastia occurred in 9% of patients receiving flutamide together with medical castration.

Pharmacokinetics

AbsorptionAnalysis of plasma, urine, and feces following a single oral 200 mg dose of tritium-labeled flutamide to human volunteers showed that the drug is rapidly and completely absorbed. Following a single 250 mg oral dose to normal adult volunteers, the biologically active alpha-hydroxylated metabolite reaches maximum plasma concentrations in about 2 hours, indicating that it is rapidly formed from flutamide. Food has no effect on the bioavailability of flutamide.DistributionIn male rats administered an oral 5 mg/kg dose of14C-flutamide neither flutamide nor any of its metabolites is preferentially accumulated in any tissue except the prostate. Total drug levels were highest 6 hours after drug administration in all tissues. Levels declined at roughly similar rates to low levels at 18 hours. The major metabolite was present at higher concentrations than flutamide in all tissues studied. Following a single 250 mg oral dose to normal adult volunteers, low plasma concentrations of flutamide were detected. The plasma half-life for the alpha-hydroxylated metabolite of flutamide is approximately 6 hours. Flutamide,in vivo, at steady-state plasma concentrations of 24 to 78 ng/mL, is 94% to 96% bound to plasma proteins. The active metabolite of flutamide, in vivo, at steady-state plasma concentrations of 1556 to 2284 ng/mL, is 92% to 94% bound to plasma proteins.MetabolismThe composition of plasma radioactivity, following a single 200 mg oral dose of tritium-labeled flutamide to normal adult volunteers, showed that flutamide is rapidly and extensively metabolized, with flutamide comprising only 2.5% of plasma radioactivity 1 hour after administration. At least six metabolites have been identified in plasma. The major plasma metabolite is a biologically active alpha-hydroxylated derivative which accounts for 23% of the plasma tritium 1 hour after drug administration. The major urinary metabolite is 2-amino-5nitro-4-(trifluoromethyl)phenol.ExcretionFlutamide and its metabolites are excreted mainly in the urine with only 4.2% of a single dose excreted in the feces over 72 hours.Plasma Pharmacokinetics of Flutamide and Hydroxyflutamide in Geriatric Volunteers (mean ± SD)Single Dose FlutamideHydroxyflutamideSteady-State FlutamideHydroxyflutamideCmax (ng/mL)25.2 ± 34.2894 ± 406113 ± 2131629 ± 586Elimination half-life (hr)---8.1 ± 1.37.89.6 ± 2.5Tmax (hr)1.9 ± 0.72.7 ± 1.01.3 ± 0.71.9 ± 0.6Cmin (ng/mL)---------673 ± 316Special PopulationsGeriatric Following multiple oral dosing of 250 mg t.i.d. in normal geriatric volunteers, flutamide and its active metabolite approached steady-state plasma levels (based on pharmacokinetic simulations) after the fourth flutamide dose. The half-life of the active metabolite in geriatric volunteers after a single flutamide dose is about 8 hours and at steady-state in 9.6 hours.Race There are no known alterations in flutamide absorption, distribution, metabolism, or excretion due to race.Renal Impairment Following a single 250 mg dose of flutamide administered to subjects with chronic renal insufficiency, there appeared to be no correlation between creatinine clearance and either Cmaxor AUC of flutamide. Renal impairment did not have an effect on the Cmaxor AUC of the biologically active alpha- hydroxylated metabolite of flutamide. In subjects with creatinine clearance of < 29 mL/min, the half-life of the active metabolite was slightly prolonged. Flutamide and its active metabolite were not well dialyzed. Dose adjustment in patients with chronic renal insufficiency is not warranted.Hepatic Impairment No information on the pharmacokinetics of flutamide in hepatic impairment is available (see BOXED WARNING, Hepatic Injury).Women, Pediatrics Flutamide has not been studied in women or pediatric subjects.Drug-Drug InteractionsInteractions between flutamide capsules and LHRH-agonists have not occurred. Increases in prothrombin time have been noted in patients receiving warfarin therapy (see PRECAUTIONS).

Clinical Studies

Flutamide has been demonstrated to interfere with testosterone at the cellular level. This can complement medical castration achieved with LHRH-agonists which suppresses testicular androgen production by inhibiting luteinizing hormone secretion.The effects of combination therapy have been evaluated in two studies. One study evaluated the effects of flutamide and an LHRH-agonist as neoadjuvant therapy to radiation in stage B2-C prostatic carcinoma and the other study evaluated flutamide and an LHRH-agonist as the sole therapy in stage D2prostatic carcinoma.Stage B2-C Prostatic CarcinomaThe effects of hormonal treatment combined with radiation was studied in 466 patients (231 flutamide capsules + goserelin acetate implant + radiation, 235 radiation alone) with bulky primary tumors confined to the prostate (stage B2) or extending beyond the capsule (stage C), with or without pelvic node involvement.In this multicentered, controlled trial, administration of flutamide capsules (250 mg t.i.d.) and goserelin acetate (3.6 mg depot) prior to and during radiation was associated with a significantly lower rate of local failure compared to radiation alone (16% vs. 33% at 4 years, P < 0.001). The combination therapy also resulted in a trend toward reduction in the incidence of distant metastases (27% vs. 36% at 4 years, P = 0.058). Median disease-free survival was significantly increased in patients who received complete hormonal therapy combined with radiation as compared to those patients who received radiation alone (4.4 vs 2.6 years, P < 0.001). Inclusion of normal PSA level as a criterion for disease-free survival also resulted in significantly increased median disease-free survival in patients receiving the combination therapy (2.7 vs. 1.5 years, P < 0.001).Stage D2 Prostatic CarcinomaTo study the effects of combination therapy in metastatic disease, 617 patients (311 leuprolide + flutamide, 306 leuprolide + placebo) with previously untreated advanced prostatic carcinoma were enrolled in a large multicentered, controlled clinical trial.Three and one-half years after the study was initiated, median survival had been reached. The median actuarial survival time was 34.9 months for patients treated with leuprolide and flutamide versus 27.9 months for patients treated with leuprolide alone. This 7 month increment represents a 25% improvement in overall survival time with the flutamide therapy. Analysis of progression-free survival showed a 2.6 month improvement in patients who received leuprolide plus flutamide, a 19% increment over leuprolide and placebo.

Indications And Usage

Flutamide capsules are indicated for use in combination with LHRH-agonists for the management of locally confined Stage B2-C and Stage D2metastatic carcinoma of the prostate.Stage B2-C Prostatic Carcinoma Treatment with flutamide capsules and the goserelin acetate implant should start eight weeks prior to initiating radiation therapy and continue during radiation therapy.Stage D2Metastatic Carcinoma To achieve benefit from treatment, flutamide capsules should be initiated with the LHRH-agonist and continued until progression.

Contraindications

Flutamide capsules are contraindicated in patients who are hypersensitive to flutamide or any component of this preparation.Flutamide capsules are contraindicated in patients with severe hepatic impairment (baseline hepatic enzymes should be evaluated prior to treatment).

Warnings

Hepatic InjurySEE BOXED WARNINGUse in WomenFlutamide capsules are for use only in men. This product has no indication for women and should not be used in this population, particularly for nonserious or nonlife-threatening conditions.Fetal toxicityFlutamide may cause fetal harm when administered to a pregnant woman (seePregnancy).Aniline toxicityOne metabolite of flutamide is 4-nitro-3-fluoro-methylaniline. Several toxicities consistent with aniline exposure, including methemoglobinemia, hemolytic anemia and cholestatic jaundice have been observed in both animals and humans after flutamide administration. In patients susceptible to aniline toxicity (e.g. persons with glucose-6-phosphate dehydrogenase deficiency, hemoglobin M disease and smokers), monitoring of methemoglobin levels should be considered.

Information For Patients

Patients should be informed that flutamide capsules and the drug used for medical castration should be administered concomitantly, and that they should not interrupt their dosing or stop taking these medications without consulting their physician.

  • Important information for patients taking flutamide capsules.Read this information carefully each time your prescription is refilled because there may be new information available. This summary does not tell you everything you need to know about flutamide therapy. Your doctor is the best source of information about your treatment. Ask your doctor about questions you have.What is flutamide therapy?Flutamide capsules, in combination with other therapies, is a treatment option for men with some types of prostate cancer.Prostate cancer results from the abnormal growth of prostate cells. Medical scientists do not know exactly what causes the abnormal cells, but age, environment, and genetics are important factors. Male hormones (“androgens”) cause the cancer to grow. The cancer growth can be slowed down by blocking the effect of androgens.The flutamide product is used together with an injection called “LHRH agonist,” as a combined treatment called “total androgen blockade.” The goal of this treatment is to reduce androgen levels and to block the effect of androgen on the tumor. The LHRH agonist reduces androgen levels. Flutamide therapy blocks the effect of androgen on the tumor.Who should not take the flutamide product?You should not take flutamide capsules if you have liver problems or if you are allergic to it. Flutamide capsules are for useonlyin men, therefore women should not take flutamide capsules.Are there important risks I should know about flutamide therapy?Some men taking the flutamide product had liver injury and needed to be hospitalized. In rare cases, men died because of liver failure while they were taking flutamide capsules. In about half of these cases, the liver failure occurred in the first 3 months that they were taking flutamide capsules.Because the flutamide product may cause liver failure,it is very important that you have all blood tests recommended by your doctor. These tests help identify whether you are having liver problems. A recommended schedule for these blood tests is: •Before starting flutamide treatment. •Every month for the first 4 months of therapy. •Periodically after the first 4 months.In addition, you shouldcall your doctor right away if you have any of the following signs or symptoms: •Loss of appetite. •Nausea and vomiting. •Stomach or abdominal pain. •Fatigue (feeling extremely tired). •Flu-like symptoms (muscle aches, soreness). •Brown urine. •jaundice (yellowing of the skin or whites of the eyes).These may be signs of liver failure.How should I take flutamide capsules?Take your flutamide capsules as your doctor has prescribed. The usual dosing is 2 capsules every 8 hours.Your doctor will determine whether flutamide therapy is right for you based on many different factors. These include how large your tumor is, how far it has spread and your physical condition. In addition to flutamide capsules, you may be getting other treatments, including regular injections of LHRH agonist or radiation therapy. Do not stop or interrupt any treatment without consulting your healthcare professional.If you miss a dose of flutamide capsules, simply continue therapy with your next scheduled dose. Do not try to make up for it by taking extra capsules.Can I take other medicines?If you are taking any other medicines, especially warfarin (a blood-thinning drug), tell your doctor before beginning flutamide therapy.What are the other possible side effects of taking flutamide capsules?In a medical study, when flutamide capsules were taken together with an LHRH agonist, the most common side effects were hot flashes, loss of sex drive (libido) and impotence. In addition, some men had diarrhea, nausea or vomiting, and breast enlargement.In another medical study, when the flutamide product was taken together with goserelin acetate (an LHRH agonist) and radiation therapy, the side effects of flutamide therapy were about the same as when radiation therapy was given alone. These included hot flashes, diarrhea, nausea and skin rash.What can I do if I get diarrhea?If you experience moderate diarrhea due to flutamide capsules, the following advice may help: •drink plenty of fluids •reduce your intake of dairy products (for example, milk, cheese, yogurt). •Increase your intake of whole grains, fruits and vegetables. •Stop laxative use. •Take nonprescription antidiarrheal medicines.If your diarrhea continues or it becomes severe, contact your doctor right away.Are there any other lab tests my doctor will be performing?Your doctor may perform other regular tests (such as the PSA blood test) to ensure that your body is responding to treatment. Ask your doctor if you have any questions about how your flutamide therapy is being monitored.Please ask your doctor about any questions concerning prostate cancer or flutamide therapy, or you can also ask for a more detailed leaflet that is written for healthcare professionals.

Laboratory Tests

Regular assessment of serum Prostate Specific Antigen (PSA) may be helpful in monitoring the patient’s response. If PSA levels rise significantly and consistently during flutamide therapy the patient should be evaluated for clinical progression. For patients who have objective progression of disease together with an elevated PSA, a treatment period free of antiandrogen while continuing the LHRH analogue may be considered.

Drug Interactions

Increases in prothrombin time have been noted in patients receiving long-term warfarin therapy after flutamide was initiated. Therefore close monitoring of prothrombin time is recommended and adjustment of the anticoagulant dose may be necessary when flutamide capsules are administered concomitantly with warfarin.

Carcinogenesis And Mutagenesis And Impairment Of Fertility

In a 1 year dietary study in male rats, interstitial cell adenomas of the testes were present in 49% to 75% of all treated rats (daily doses of 10, 30, and 50 mg/kg/day were administered). These produced plasma Cmaxvalues that are 1, 2, 3, and 4 fold respectively, those associated with therapeutic doses in humans. In male rats similarly dosed for 1 year, tumors were still present after 1 year of a drug-free period, but the incidences were 43% to 47%. In a 2 year carcinogenicity study in male rats, daily administration of flutamide at these same doses produced testicular interstitial cell adenomas in 91% to 95% of all treated rats as opposed to 11% of untreated control rats. Mammary adenomas, adenocarcinomas, and fibroadenomas were increased in treated male rats at exposure levels that were 1 to 4 fold those observed during therapeutic dosing in humans. There are likewise reports of malignant breast neoplasms in men treated with flutamide capsules (see ADVERSE REACTIONS section).Flutamide did not demonstrate DNA modifying activity in the Ames Salmonella/microsome -- observed during a 6 week study of flutamide monotherapy in normal human volunteers.Flutamide did not affect estrous cycles or interfere with the mating behavior of male and female rats when the drug was administered at 25 and 75 mg/kg/day prior to mating. Males treated with 150 mg/kg/day (30 times the minimum effective antiandrogenic dose) failed to mate; mating behavior returned to normal after dosing was stopped. Conception rates were decreased in all dosing groups. Suppression of spermatogenesis was observed in rats dosed for 52 weeks at approximately 3, 8, or 17 times the human dose and in dogs dosed for 78 weeks at 1.4, 2.3, and 3.7 times the human dose.

Animal Toxicology

Serious cardiac lesions were observed in 2/10 beagle dogs receiving 25 mg/kg/day for 78 weeks and 3/16 receiving 40 mg/kg/day for 2 to 4 years. These lesions, indicative of chronic injury and repair processes, included chronic myxomatous degeneration, intra-atrial fibrosis, myocardial acidophilic degeneration, vasculitis and perivasculitis. The doses at which these lesions occurred were associated with 2-hydroxyflutamide levels that were 1 to 12 fold greater than those observed in humans at therapeutic levels.

Pregnancy Category D

There was decreased 24 hour survival in the offspring of pregnant rats treated with flutamide at doses of 30, 100 or 200 mg/kg/day (approximately 3, 9 and 19 times the human dose). A slight increase in minor variations in the development of the sternebrae and vertebrae was seen in fetuses of rats treated with two higher doses. Feminization of the male rats also occurred at the two higher dose levels. There was a decreased survival rate in the offspring of rabbits receiving the highest dose (15 mg/kg/day, equal to 1.4 times the human dose).

Adverse Reactions

Stage B2-C Prostatic Carcinoma Treatment with flutamide capsules and the goserelin acetate implant did not add substantially to the toxicity of radiation treatment alone. The following adverse experiences were reported during a multicenter clinical trial comparing flutamide + goserelin acetate implant + radiation versus radiation alone. The most frequently reported (greater than 5%) adverse experiences are listed below:Adverse Events During Acute Radiation Therapy(within first 90 days of radiation therapy)(n=231) Goserelin Acetate Implant + Flutamide + Radiation(n=235) Radiation Only % All% AllRectum/Large Bowel8076Bladder5860Skin3737Adverse Events During Late Radiation Phase(after 90 days of radiation therapy) (n=231) Goserelin Acetate Implant + Flutamide + Radiation(n=235) Radiation Only % All% AllDiarrhea3640Cystitis1616Rectal Bleeding1420Proclitis88Hematuria712Additional adverse event data were collected for the combination therapy with radiation group over both the hormonal treatment and hormonal treatment plus radiation phases of the study. Adverse experiences occurring in more than 5% of patients in this group, over both parts of the study, were hot flashes (46%), diarrhea (40%), nausea (9%), and skin rash (8%).Stage D2 Metastatic Carcinoma The following adverse experiences were reported during a multicenter clinical trial comparing flutamide + LHRH agonist versus placebo + LHRH agonist.The most frequently reported (greater than 5%) adverse experiences during treatment with flutamide capsules in combination with an LHRH agonist are listed in the table below. For comparison, adverse experiences seen with an LHRH agonist and placebo are also listed in the following table. (n=294) Flutamide + LHRH agonist(n=28) Placebo + LHRH agonist % All% AllHot Flashes6157Loss of Libido3631Impotence3329Diarrhea124Nausea/Vomiting1110Gynecomastia911Other79Other GI64As shown in the table, for both treatment groups, the most frequently occurring adverse experiences (hot flashes, impotence, loss of libido) were those known to be associated with low serum androgen levels and known to occur with LHRH agonists alone.The only notable difference was the higher incidence of diarrhea in the flutamide + LHRH agonist group (12%), which was severe in 5% as opposed to the placebo + LHRH agonist (4%), which was severe in less than 1%.In addition, the following adverse reactions were reported during treatment with flutamide + LHRH agonist.Cardiovascular System:hypertension in 1% of patients.Central Nervous System: CNS (drowsiness/confusion/depression/anxiety/nervousness) reactions occurred in 1% of patients.Gastrointestinal System: anorexia 4%, and other GI disorders occurred in 6% of patients.Hematopoietic System: anemia occurred in 6%, leukopenia in 3%, and thrombocytopenia in 1% of patients.Liver and Biliary System: hepatitis and jaundice in less than 1% of patients.Skin: irritation at the injection site and rash occurred in 3% of patients.Other:edema occurred in 4%, genitourinary and neuromuscular symptoms in 2%, and pulmonary symptoms in less than 1% of patients.In addition, the following spontaneous adverse experiences have been reported during the marketing of flutamide: hemolytic anemia,macrocytic anemia,methemoglobinemia, sulfhemoglobinemia, photosensitivity reactions (including erythema, ulceration, bullous eruptions, and epidermal necrolysis) and urine discoloration. The urine was noted to change to an amber or yellow-green appearance which can be attributed to the flutamide and/or its metabolites. Also reported were cholestatic jaundice, hepatic encephalopathy, and hepatic necrosis. The hepatic conditions were often reversible after discontinuing therapy; however, there have been reports of death following severe hepatic injury associated with use of flutamide.Malignant breast neoplasms have occurred rarely in male patients being treated with flutamide capsules.Abnormal Laboratory Test Values: Laboratory abnormalities including elevated SGOT, SGPT, bilirubin values, SGGT, BUN, and serum creatinine have been reported.

Overdosage

In animal studies with flutamide alone, signs of overdose included hypoactivity, piloerection, slow respiration, ataxia, and/or lacrimation, anorexia, tranquilization, emesis, and methemoglobinemia.Clinical trials have been conducted with flutamide in doses up to 1500 mg per day for periods up to 36 weeks with no serious adverse effects reported. Those adverse reactions reported included gynecomastia, breast tenderness, and some increases in SGOT. The single dose of flutamide ordinarily associated with symptoms of overdose or considered to be life-threatening has not been established.Flutamide is highly protein bound, and is not cleared by hemodialysis. 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 And Administration

The recommended dosage is 2 capsules 3 times a day at 8 hour intervals for a total daily dose of 750 mg.

How Supplied

Flutamide capsules USP, 125 mg, are available as opaque, beige/beige capsules, imprinted “par/753”on the cap and body. They are available in: Bottles of 180 (NDC 60429-272-18) Bottles of 500 (NDC 60429-272-05) Manufactured By: PAR PHARMACEUTICAL COMPANIES, INC. Spring Valley, NY 10977Marketed/Packaged by: GSMS, Inc. Camarillo, CA 93012

Storage

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).Rev. Nov 3, 2011

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