Nilandron (nilutamide)

Nilutamide is a nonsteroidal antiandrogen.

Nilutamide is a nonsteroidal antiandrogen that is structurally and pharmacologically related to bicalutamide and flutamide.

Nilutamide is a pure antiandrogen, possessing no intrinsic hormonal activity; the antiandrogenic mechanism of action of the drug is via androgen-receptor antagonism. Nilutamide 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. Nilutamide is a selective antiandrogen with no estrogenic, antiestrogenic, progestational, antiprogestational, or adrenocortical activity in various animal models.

The relative binding affinity of nilutamide at the androgen receptor is less than that of bicalutamide, but similar to that of hydroxyflutamide, the active metabolite of 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 effects of the drugs. Androgen receptors in the hypothalamus are blocked by nilutamide, 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.

Following multiple doses of 150 mg nilutamide twice daily, steady state is attained in most patients within 2-4 weeks. After multiple doses, the AUC was shown to be 110% higher than the AUC obtained from a single 150 mg dose, indicating that with multiple doses, metabolic enzyme inhibition may occur. Based on blood, urine, and fecal samples in patients with metastatic prostate cancer, nilutamide has been shown to be rapidly and completely absorbed.

Nilutamide moderately binds to plasma proteins, and exhibits low binding to erythrocytes. Studies indicate that nilutamide does not exhibit nonlinear pharmacokinetics. Nilutamide undergoes extensive metabolism in the liver and lungs by CYP isoenzymes, with less than 2% of radiolabeled drug excreted unchanged in the urine after 5 days.

Five metabolites of nilutamide have been isolated from human urine; however, the pharmacokinetics and pharmacodynamics of these metabolites have not been fully investigated. Following oral administration of a single 150 mg radiolabeled dose of nilutamide, 62% of the dose is eliminated in the urine during the first 5 days; however, excretion of radioactivity in the urine likely extends beyond this period. After 4-5 days, 1.4%-7% of the nilutamide dose is eliminated in the feces.

The mean elimination half-life of nilutamide based on a single dose of 100-300 mg ranged from 38-59.1 hours, with most values ranging from 41-49 hours; however, the half-life of one metabolite of nilutamide ranges from 59-126 hours.

USES: This medication is used to treat prostate cancer. Nilutamide belongs to a class of drugs known as anti-androgens (anti-testosterone). Testosterone, a natural hormone, helps prostate cancer to grow and spread.

Nilutamide works by blocking the effects of testosterone, thereby slowing the growth and spread of prostate cancer.

Generic name: nilutamide
Pronunciation: (nye-LOO-tuh-mide)
Drug class: Antiandrogen
Therapeutic class: Antineoplastics

The following indications are listed for Nilandron:

• Metastatic Prostate Carcinoma

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