Flutamide is available as 250 mg tablets. It is an anti-androgen that inhibits the action of testosterone. It is primarily used in the treatment of prostate cancer. As an anti-androgen, it has also been used in the treatment of acne and excessive hair growth in women.

Indications of Flutamide:

• Prostate carcinoma:

  • It is indicated for the management of locally confined Stage B to C and Stage D metastatic prostate cancer (in combination with a luteinizing hormone-releasing hormone [LHRH] agonist).
  • For Stage B to C prostate cancer, flutamide treatment (and goserelin) should start 8 weeks before starting radiation therapy and continue during radiation therapy.
  • For maximum treatment benefit in Stage D metastatic prostate cancer, flutamide therapy should be started with the LHRH agonist and continued until disease progression.

Bicalutamide (Casodex) is another anti-androgen used in the treatment of prostate cancer.

Flutamide dose in adults:

Flutamide dose in the treatment of metastatic prostate cancer:

• 250 mg per oral three times a day (every 8 hours).

Use in Children:

Not indicated.

Pregnancy Risk Factor D

• Studies on animal reproduction revealed negative outcomes.
• Therapy can cause fetal harm during pregnancy.
• It is not recommended for use by women.

Flutamide use during breastfeeding:

• According to the manufacturer, it is not recommended for use by women.
• It is not possible to find information about its use by breastfeeding mothers.

Dose adjustment in renal disease:

No dosage adjustment is necessary for patients with chronic renal insufficiency.

Flutamide Dose adjustment in liver disease:

• Mild to moderate impairment:

  • There are no dosage adjustments provided in the manufacturer’s labeling.

• Severe impairment:

  • Use is contraindicated.

Common Side Effects of Flutamide:

• Endocrine & Metabolic:

  • Hot Flash
  • Galactorrhea
  • Decreased Libido
  • Increased Lactate Dehydrogenase

• Gastrointestinal:

  • Diarrhea
  • Vomiting

• Genitourinary:

  • Impotence
  • Cystitis
  • Breast Tenderness

• Hematologic & Oncologic:

  • Rectal Hemorrhage
  • Tumor Flare

• Hepatic:

  • Increased Serum AST

Rare Side Effects Of Flutamide:

• Cardiovascular:

  • Edema
  • Hypertension

• Central Nervous System:

  • Anxiety
  • Confusion
  • Depression
  • Dizziness
  • Drowsiness
  • Headache
  • Insomnia
  • Nervousness

• Dermatologic:

  • Skin Rash
  • Ecchymoses
  • Pruritus

• Endocrine & Metabolic:

  • Gynecomastia

• Gastrointestinal:

  • Nausea
  • Proctitis
  • Gastric Distress
  • Anorexia
  • Constipation
  • Dyspepsia
  • Increased Appetite

• Genitourinary:

  • Hematuria

• Hematologic & Oncologic:

  • Anemia
  • Leukopenia
  • Thrombocytopenia

• Infection:

  • Herpes Zoster

• Neuromuscular & Skeletal:

  • Weakness

Contraindications to Flutamide:

Hypersensitivity to any drug or component of the formulation Severe liver dysfunction (evaluate baseline enzymes before treatment).

Warnings and precautions

• Gynecomastia

  • Males can experience gynecomastia by using flutamide therapy with medical castration.

• Hepatic failure: [U.S. Boxed Warning]:

  • Flutamide therapy can cause transaminitis and hepatic-encephalopathy, as well as jaundice and transaminitis.
  • Flutamide therapy is 50% effective in reducing hepatotoxicity within the first three months. In some cases, stopping the therapy can reverse hepatotoxicity.
  • Monitoring serum transaminase levels at baseline should be done monthly for four months and then periodically thereafter.
  • Liver function tests should be performed if you have symptoms such as nausea, vomiting, stomach pain, fatigue, anorexia or "flu-like", jaundice, right upper quadrant tenderness and raised bilirubin. This is consistent with hepatic dysfunction.
  • Therapy should be stopped for patients with ALT values exceeding 2x the upper normal limit.
  • Therapy should be stopped immediately if ALT is above 2x the upper normal limit.
  • Hospitalization for liver dysfunction can lead to death, but it is not common.
  • Therapy is not recommended for patients suffering from severe hepatic impairment.

• Cardiovascular disease

  • Therapy with androgen deprivation increases the risk of cardiovascular disease.

• Hemoglobin M Disease:

  • Patients with hemoglobin M disorder have a significantly higher risk of developing toxicities from aniline exposure.
  • Therefore, it is important to monitor methemoglobin levels closely.

Flutamide: Drug Interaction

Monitoring parameters:

• PSA (prostate-specific antigen LFTs monitoring in case of symptoms including nausea, vomiting, abdominal pain, fatigue, anorexia, flu-like symptoms, hyperbilirubinemia, jaundice, or right upper quadrant tenderness. Serum transaminases (at baseline, monthly for 4 months, and periodically thereafter).

How to administer Flutamide?

It can be taken orally with or without food. It should be given in three divided doses.

Mechanism of action of Flutamide:

Nonsteroidal antiandrogen, it works by blocking androgen uptake in the target tissues and/or inhibiting androgen binding.

Absorption: Oral:

• Rapid and complete.

Protein binding:

• Parent drug: 94% to 96%; 2-hydroxyflutamide: 92% to 94%.

Metabolism:

• Extensively hepatic to ≥6 metabolites, primarily 2-hydroxyflutamide (active).

Half-life elimination:

• 6 hours (2-hydroxyflutamide).

Time to peak:

• 2 hours (2-hydroxyflutamide).

Excretion:

• Primarily urine (as metabolites);
• feces (~4%).

International Brands of Flutamide:

• DOM-Flutamide
• Euflex
• NU-Flutamide
• PMS-Flutamide
• TEVA-Flutamide
• Androxine
• Bedozane
• Curestat
• Cytomid
• Cytomid-250
• Drogenil
• Etaconil
• Eulexin
• Eulexine
• Eumide
• Flucinom
• Flucinome
• Flugerel
• Fluken
• Flulem
• Flumid
• Fluta-Cell
• Flutacan
• Flutafarm
• Flutam
• Flutamex
• Flutamid
• Flutamid Abbott
• Flutamin
• Flutan
• Flutanon
• Flutaplex
• Flutasin
• Flutax
• Flutexine
• Flutrax
• Fluxus
• Fugerel
• Fuprostatel
• Grisetin
• Profamid
• Proscant
• Prostacur
• Prostalex
• Prostica
• Tafenil

Flutamide brands in Pakistan: