Flutamide (flutamide)

Flutamide, a nonsteroidal antiandrogen, is an antineoplastic agent.

Flutamide, a toluidine derivative, is a nonsteroidal antiandrogen that is structurally and pharmacologically related to bicalutamide and nilutamide.

Flutamide is a pure antiandrogen, possessing no intrinsic hormonal activity; the antiandrogenic mechanism of action of the drug is via androgen-receptor antagonism. Flutamide inhibits the action of androgens by competitively blocking nuclear androgen receptors in target tissues such as the prostate, seminal vesicles, and adrenal cortex; 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. Flutamide is a selective antiandrogen with no estrogenic, antiestrogenic, progestational, antiprogestational, antigonadotropic, or adrenocortical activity in various animal models.

Flutamide is metabolized in vivo to 2-hydroxyflutamide, which appears to be principally responsible for the antiandrogenic activity; this metabolite is a potent competitive inhibitor of androgen-receptor binding, exhibiting 1.5 times the antiandrogenic potency of flutamide in animal models. The relative binding affinity of 2-hydroxyflutamide at the androgen receptor is less than that of bicalutamide but similar to that of nilutamide. In addition to blocking the binding of dihydrotestosterone (DHT) at androgen receptors, flutamide inhibits androgen uptake into target cells, and decreases the number of intraprostatic androgen receptors by secondarily (i.e., subsequent to DHT-binding blockade) preventing translocation of the androgen-receptor complex into cellular nuclei.

Metabolism of adrenal androgen precursors of testosterone (e.g., dehydroepiandrosterone (DHEA)) to inactive metabolites increases in castrated patients with prostatic cancer receiving flutamide.

Common pharmacologic therapies for prostate cancer (i.e., gonadotropin-releasing hormone (GnRH) analogs, nonsteroidal antiandrogens) when used as monotherapy initially result in increased serum testosterone concentrations, which may limit the effect of the drug. Androgen receptors in the hypothalamus are blocked by flutamide, which disrupts the inhibitory feedback of testosterone on luteinizing hormone (LH) release, resulting in a temporary increase in secretion of LH; the increase in LH stimulates an increase in the production of testosterone. As GnRH analogs have potent GnRH agonist properties, testicular steroidogenesis continues during the first few weeks after initiating therapy.

However, the combination of orchiectomy or GnRH analog therapy to suppress testicular androgen production and an antiandrogen to block response of remaining adrenal androgens provides maximal androgen blockade. Concomitant administration of antiandrogens such as nilutamide in patients initiating therapy with a GnRH analog can inhibit initial androgenic stimulation and potential exacerbation of symptoms (e.g., bone pain, urinary obstruction, liver pain, impending spinal cord compression) that may occur during the first month of GnRH analog therapy. (See Cautions in Leuprolide Acetate 10:00.)

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USES: 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.

Generic name: flutamide
Pronunciation: (FLEW-tuh-mide)

The following indications are listed for Flutamide:

• Prostatic Carcinoma

Also known as: Malignancy Of Prostate, Malignant Neoplasm Of Prostate, Malignant Tumor Of Prostate, Prostate Cancer.

No ICD codes are available for this drug.