Flutamide

Name: Flutamide

Warnings

Black Box Warnings

Hospitalization and rarely death have been reported due to hepatic failure associated with flutamide use. Hepatic failure may occur within 3 months of therapy initiation. The hepatic injury may be reversible in some patients following the discontinuation of therapy

Perform liver function tests if symptoms suggestive of liver dysfunction (eg, abdominal pain, fatigue, anorexia, flu-like symptoms, nausea, vomiting, jaundice, hyperbilirubinuria, right upper quadrant tenderness) occur

Discontinue therapy if patient develops jaundice or ALT rises above 2 times the upper limit of normal

Contraindications

Hypersensitivity, severe hepatic disease

Cautions

Risk of severe liver injury

Potential for aniline toxicity (methemoglobinemia, hemolytic anemia etc); specially monitor patients sensitive to aniline toxicity

Risk for cardiovascular disease may increase with androgen deprivation

Pharmacology

Mechanism of Action

Nonsteroidal antiandrogen, competitively binds androgen receptors and inhibits testosterone stimulation of cell growth in prostate cancer

Pharmacokinetics

Half-Life: 6 hr

Peak Plasma Time: 6 hr

Protein Bound: 94-96%

Metabolism: Liver

Metabolites: 4-nitro-3-fluoro-methylaniline, 2-amino- 5-nitro- 4-(trifluoromethyl) phenol

Excretion: Primarily urine; <5% in feces

Dialyzable: No

Flutamide Food Interactions

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of flutamide, there are no specific foods that you must exclude from your diet when receiving this medication. 

Flutamide and Lactation

According to the manufacturer, this product is not indicated for use in women. Information related to use in nursing women has not been located.

Actions

  • A selective antiandrogen with no estrogenic, antiestrogenic, progestational, antiprogestational, antigonadotropic, or adrenocortical activity in various animal models.3

  • Competitively blocks nuclear androgen receptors in target tissues (e.g., prostate, seminal vesicles, adrenal cortex).1 3 8 9 10 11 12 24 25

  • Blockade of androgen receptors in the hormone-sensitive tumor cells may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis.1 3 8 9 10 11 12 24 25

  • Inhibits initial androgenic stimulation and potential exacerbation of symptoms (e.g., bone pain, urinary obstruction, liver pain, impending spinal cord compression) associated with the first month of LHRH analog therapy.6 10 11 18

Uses For flutamide

Flutamide is used together with a luteinizing hormone-releasing hormone (LHRH) agonist to treat metastatic (cancer that has spread) prostate cancer in men. Flutamide belongs to the group of medicines called antiandrogens. It works by blocking the effects of androgen (a male hormone), to stop the growth and spread of cancer cells.

flutamide is available only with your doctor's prescription.

What are some other side effects of Flutamide?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Hot flashes.
  • Upset stomach or throwing up.
  • Enlarged breasts.
  • Lowered interest in sex.
  • Change in sex ability.
  • Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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 capsules + 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

Adverse Events During Late Radiation Phase

(within first 90 days of radiation therapy)

(after 90 days of radiation therapy)

 

(n = 231)

(n = 235)

 

(n = 231)

(n = 235)

 

Goserelin Acetate Implant + Flutamide Capsules + Radiation

Radiation Only

 

Goserelin Acetate Implant + Flutamide Capsules + Radiation

Radiation Only

 

% All

% All

 

% All

% All

Rectum/large

bowel

80

76

Diarrhea

36

40

Bladder

58

60

Cystitis

16

16

Skin

37

37

Rectal

bleeding

14

20

Proctitis

8

8

Hematuria

7

12

Additional adverse event data was 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 capsules + 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)

(n = 285)

 

Flutamide + LHRH agonist

Placebo + LHRH agonist

 

% All

% All

Hot flashes

61

57

Loss of libido

36

31

Impotence

33

29

Diarrhea

12

4

Nausea/vomiting

11

10

Gynecomastia

9

11

Other

7

9

Other GI

6

4

As 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.

Abnormal Laboratory Test Values

Laboratory abnormalities including elevated SGOT, SGPT, bilirubin values, SGGT, BUN, and serum creatinine have been reported.

Package/Label Display Panel

Flutamide Capsules USP 125 mg, 500s Label Text

NDC 0172-4960-70

Flutamide

Capsules USP

125 mg

PHARMACIST: PLEASE DISPENSE WITH ATTACHED

PATIENT INFORMATION LEAFLET

Rx only

500 CAPSULES

TEVA

Flutamide 
Flutamide capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0172-4960
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Flutamide (Flutamide) Flutamide 125 mg
Inactive Ingredients
Ingredient Name Strength
FERROSOFERRIC OXIDE  
STARCH, CORN  
D&C YELLOW NO. 10  
FD&C BLUE NO. 1  
FD&C BLUE NO. 2  
FD&C RED NO. 40  
GELATIN, UNSPECIFIED  
LACTOSE MONOHYDRATE  
MAGNESIUM STEARATE  
FERRIC OXIDE RED  
SODIUM LAURYL SULFATE  
TITANIUM DIOXIDE  
FERRIC OXIDE YELLOW  
Product Characteristics
Color BROWN (light brown) Score no score
Shape CAPSULE Size 22mm
Flavor Imprint Code 4960
Contains     
Packaging
# Item Code Package Description
1 NDC:0172-4960-60 100 CAPSULE in 1 BOTTLE
2 NDC:0172-4960-58 180 CAPSULE in 1 BOTTLE
3 NDC:0172-4960-70 500 CAPSULE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA075780 09/19/2001 05/31/2018
Labeler - Teva Pharmaceuticals USA, Inc. (001627975)
Revised: 01/2017   Teva Pharmaceuticals USA, Inc.

Pharmacologic Category

  • Antineoplastic Agent, Antiandrogen

Special Populations Elderly

The half-life is slightly prolonged, ~9.6 hours (active metabolite at steady state)

Contraindications

Hypersensitivity to flutamide or any component of the formulation; severe hepatic impairment (evaluate baseline hepatic enzymes prior to treatment).

Dosing Adult

Prostate cancer, metastatic: Males: Oral: 250 mg 3 times daily (every 8 hours)

Pregnancy Risk Factor D Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. May cause fetal harm if administered in pregnancy. Flutamide is not indicated for use in women.

Usual Adult Dose for Prostate Cancer

For use in locally confined stage B2-C and stage D2 metastatic carcinoma of the prostate: 250 mg orally every 8 hours.

Liver Dose Adjustments

Data not available.

Other Comments

Doses > 750 mg/day are not recommended. When treating B2-C prostatic carcinoma, flutamide and LHRH agonists should be started 8 weeks prior to initiating radiation therapy and continued during radiation therapy. When treating single stage D2 metastatic carcinoma, flutamide should be initiated with the LHRH agonist and continued until progression.

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