Flutamide – Uses, Dosage, Side Effects, Interaction

Flutamide is a nonsteroidal antiandrogen. In animal studies, flutamide demonstrates potent antiandrogenic effects. It exerts its antiandrogenic action by inhibiting androgen uptake and/or by inhibiting the 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.

Indications

  • For the management of locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate
  • Flutamide is a nonsteroidal antiandrogen that acts by binding to and blocking intracellular androgen receptors in target tissues including testes, prostate, skin, and hair follicles.
  • Flutamide is approved to treat: Prostate cancer that may be locally advanced or has metastasized (spread to other parts of the body). It is used with a type of drug called a luteinizing hormone-releasing hormone agonist. Flutamide is also being studied in the treatment of other conditions and types of cancer.
  • Antineoplastic agents are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on the removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias
  • Flutamide has been used in case reports to decrease the frequency of spontaneous orgasms, for instance in men with post-orgasmic illness syndrome
  • Flutamide has been researched and used extensively in the treatment of androgen-dependent skin and hair conditions in women including acne, seborrhea, hirsutism, and scalp hair loss, as well as in hyperandrogenism (e.g., in polycystic ovary syndrome or congenital adrenal hyperplasia), and is effective in improving the symptoms of these conditions.
  • Flutamide has been found to be effective in the treatment of acne and seborrhea in women in a number of studies.[rx][rx] In a long-term study of 230 women with acne, 211 of whom also had seborrhea, very-low-dose flutamide alone or in combination with an oral contraceptive caused a marked decrease in acne and seborrhea after 6 months of treatment, with maximal effect by 1 year of treatment and benefits maintained in the years thereafter
  • Flutamide has been found to be effective in the treatment of hirsutism (excessive body/facial hair growth) in numerous studies.[rx][rx] It possesses moderate effectiveness for this indication, and the overall quality of the evidence is considered to be moderate
  • Flutamide has been found to be effective in the treatment of female pattern hair loss in a number of studies. In one study of 101 pre- and postmenopausal women, flutamide alone or in combination with an oral contraceptive produced a marked decrease in hair loss scores after 1 year of treatment, with maximum effect after 2 years of treatment and benefits maintained for another 2 years

Use in Cancer

Flutamide is approved to treat:

Flutamide is also being studied in the treatment of other conditions and types of cancer.

Contraindications

  • glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • deficiency of the blood enzyme cytochrome b5 reductase
  • methemoglobinemia, a type of blood disorder
  • liver failure
  • liver problems
  • severe liver disease
  • high amount of bilirubin in the blood
  • abnormal liver function tests
  • pregnancy
  • a patient who is producing milk and breastfeeding
  • anemia from pyruvate kinase and G6PD deficiencies

Dosage

Strengths: 125 mg, 250 mg

Prostate Cancer

  • 250 mg orally every 8 hours
  • This drug may be taken with or without food.
  • Stage B2-C Prostatic Carcinoma: Treatment with this drug and the goserelin acetate implant starts 8 weeks prior to initiating radiation therapy and continues during radiation therapy.
  • Stage D2 Metastatic Carcinoma: This drug should be initiated with the LHRH-agonist and continued until progression.
  • Locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate

Side Effects

The Most Common

  • diarrhea
  • nausea
  • vomiting
  • loss of appetite
  • hot flashes
  • decrease in sexual ability or desire
  • breast enlargement in men
  • drowsiness
  • confusion
  • depression
  • anxiety
  • swelling of the hands, feet, ankles, or lower legs
  • blue-green or orange-colored urine
  • nausea, upper stomach pain, loss of appetite;
  • itching, tiredness, flu-like symptoms;
  • dark urine, clay-colored stools; or
  • jaundice (yellowing of the skin or eyes).
  • breast swelling or tenderness;
  • hot flashes;
  • vomiting, nausea, diarrhea; or
  • impotence, loss of interest in sex.

More common

  • Black, tarry stools
  • bloody or cloudy urine
  • continuing diarrhea
  • continuing stomach pain
  • difficult, burning, or painful urination
  • frequent urge to urinate
  • pale skin
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • appetite changes
  • constipation
  • diarrhea
  • dizziness
  • drowsiness
  • headache
  • hot flashes
  • impotence
  • nausea
  • indigestion
  • nervousness
  • reduction in sexual desire
  • sleeping problems
  • swelling of breasts with pain or tenderness
  • vomiting

Rare

  • Blurred vision
  • chest pain
  • chills
  • cough
  • difficulty with breathing
  • dizziness
  • drowsiness
  • fever
  • headache
  • nervousness
  • pounding in the ears
  • shortness of breath
  • slow or fast heartbeat
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • swelling
  • swollen glands
  • Abdominal or stomach pain
  • clay-colored stools
  • dark urine
  • general tiredness and weakness
  • itching
  • light-colored stools
  • loss of appetite
  • nausea and vomiting
  • rash
  • tumor
  • unpleasant breath odor
  • upper right abdominal pain
  • vomiting of blood
  • yellow eyes and skin
  • Back, leg, or stomach pains
  • bleeding gums
  • blistering, peeling, or loosening of the skin
  • bluish-colored lips, fingernails, or palms
  • discoloration of the urine
  • dizziness or lightheadedness
  • flushing or redness of the skin
  • general body swelling
  • headache
  • itching
  • joint or muscle pain
  • nosebleeds
  • rapid heart rate
  • red irritated eyes
  • red skin lesions, often with a purple center
  • unusually warm skin

Drug interaction

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Pregnancy and Lactation

FDA Pregnancy Category D

Pregnancy

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).

Lactation

  • This drug is not indicated for use in females.
  • Excreted into human milk: Unknown
  • Excreted into animal milk: Data not available
  • The effects in the nursing infant are unknown.

How should this medicine be used?

Flutamide comes as a capsule to take by mouth. It is usually taken with or without food every 8 hours (three times a day.) Take flutamide at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take flutamide exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Continue to take flutamide along with the LHRH agonist treatment even if you feel well. Do not stop taking either medication without talking to your doctor. Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient.

What special precautions should I follow?

Before taking flutamide,

  • tell your doctor and pharmacist if you are allergic to flutamide or any other medications.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention anticoagulants (”blood thinners”) such as warfarin (Coumadin).
  • tell your doctor if you smoke and if you have or have ever had any inherited blood diseases such as glucose-6-phosphate dehydrogenase (G-6-PD) deficiency or hemoglobin M disease.
  • you should know that flutamide is only for use in men. If taken by pregnant women, flutamide can harm the fetus. Women who are or may become pregnant should not take flutamide. If you take flutamide while you are pregnant, call your doctor.
  • ask your doctor about the safe use of alcoholic beverages while you are taking flutamide. Flutamide may cause facial flushing, and drinking alcohol can make it worse.

References

  1. https://www.accessdata.fda.gov/spl/data/6c1fd5b4-b5c7-4e48-8bb1-36f0cacf6f42/6c1fd5b4-b5c7-4e48-8bb1-36f0cacf6f42.xml
  2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/18554s23lbl.pdf
  3. https://pubchem.ncbi.nlm.nih.gov/compound/Flutamide
  4. https://www.cancer.gov/about-cancer/treatment/drugs/flutamide
  5. https://go.drugbank.com/drugs/DB00499
  6. https://www.drugs.com/flutamide.html
  7. https://www.ncbi.nlm.nih.gov/books/NBK482215/
  8. https://www.mayoclinic.org/drugs-supplements/flutamide-oral-route/side-effects/drg-20072536
  9. https://medlineplus.gov/druginfo/meds/a697045.html
  10. https://en.wikipedia.org/wiki/Flutamide
  11. https://www.webmd.com/drugs/2/drug-1549/flutamide-oral/details/list-contraindications
  12. ChemIDplus Chemical Information Classification
  13. CompTox Chemicals Dashboard Chemical Lists
  14. PubChem
  15. Antineoplastic Agents, Hormonal
  16. Therapeutic category of drugs in Japan
    Anatomical Therapeutic Chemical (ATC) classification
    Target-based classification of drugs
    Drugs listed in the Japanese Pharmacopoeia
  17. NCBI