Nilandron

Cytostatic Androgen Receptor Antagonists

Nilutamide is administered with or without food.

visual impairment / Early / 0-56.9
heart failure / Delayed / 3.0-3.0
GI bleeding / Delayed / 2.0-2.0
aplastic anemia / Delayed / 0-1.0
pulmonary fibrosis / Delayed / 0-1.0

hot flashes / Early / 28.4-66.5
constipation / Delayed / 7.1-19.6
testicular atrophy / Delayed / 16.3-16.3
elevated hepatic enzymes / Delayed / 3.0-12.9
peripheral edema / Delayed / 12.4-12.4
impotence (erectile dysfunction) / Delayed / 11.0-11.0
dyspnea / Early / 6.2-10.5
hypertension / Early / 5.3-9.1
depression / Delayed / 8.6-8.6
hematuria / Delayed / 8.1-8.1
anemia / Delayed / 7.2-7.2
chest pain (unspecified) / Early / 7.2-7.2
bone pain / Delayed / 6.2-6.2
hypotension / Rapid / 0-5.0
hyperglycemia / Delayed / 4.0-4.0
leukopenia / Delayed / 3.0-3.0
photophobia / Early / 2.0-2.0
cataracts / Delayed / 2.0-2.0
melena / Delayed / 2.0-2.0
edema / Delayed / 2.0-2.0
angina / Early / 2.0-2.0
pneumonitis / Delayed / 2.0-2.0
jaundice / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known

nausea / Early / 9.8-23.9
asthenia / Delayed / 19.1-19.1
insomnia / Early / 16.3-16.3
headache / Early / 13.9-13.9
back pain / Delayed / 11.5-11.5
anorexia / Delayed / 11.0-11.0
libido decrease / Delayed / 11.0-11.0
gynecomastia / Delayed / 10.5-10.5
abdominal pain / Early / 10.0-10.0
dizziness / Early / 7.1-10.0
infection / Delayed / 5.3-8.6
influenza / Delayed / 7.2-7.2
dyspepsia / Early / 6.7-6.7
nocturia / Early / 6.7-6.7
hyperhidrosis / Delayed / 6.2-6.2
alopecia / Delayed / 5.7-5.7
vomiting / Early / 5.7-5.7
rash / Early / 5.3-5.3
hypoesthesia / Delayed / 5.3-5.3
fever / Early / 5.3-5.3
flushing / Rapid / 0-5.0
malaise / Early / 2.0-5.0
paresthesias / Delayed / 3.0-3.0
pruritus / Rapid / 2.0-2.0
diarrhea / Early / 2.0-2.0
xerostomia / Early / 2.0-2.0
syncope / Early / 2.0-2.0
anxiety / Delayed / 2.0-2.0
weight loss / Delayed / 2.0-2.0
rhinitis / Early / 2.0-2.0
cough / Delayed / 2.0-2.0

Nilutamide is contraindicated in patients with severe respiratory insufficiency. Nilutamide therapy has been associated with interstitial pneumonitis. Reports of interstitial changes including pulmonary fibrosis that led to hospitalization and death have been reported rarely post-marketing. Symptoms included exertional dyspnea, cough, chest pain, and fever. Chest radiographs (X-rays) showed interstitial or alveolo-interstitial changes, and pulmonary function tests revealed a restrictive pattern with decreased diffusing capacity of the lung (DLco). A routine baseline chest X-ray should be performed before treatment. Baseline pulmonary function tests may be considered. Patients should be told to report immediately any new or worsening shortness of breath. Nilutamide therapy should be interrupted until it can be determined if the respiratory symptoms are drug related. Most cases occur within the first 3 months of therapy, and are reversible with drug discontinuation. Also, because interstitial pneumonitis was reported in 8 of 47 patients (17%) in a small study performed in Japan, specific caution should be observed in the treatment of Asian patients.

Nilandron

Rx

Oral antiandrogen; used for metastatic prostate CA; similar in action to bicalutamide and flutamide; differs from steroidal antiandrogens (e.g., finasteride) in that nilutamide is specific for the androgen receptor.

Beginning no later than post-op day 1, 300 mg PO once daily for 30 days, then 150 mg PO once daily.

Nilutamide is contraindicated for use in patients with severe hepatic disease. If during treatment, the ALT rises to > 2—3x the upper limit of normal, discontinue nilutamide and monitor liver function tests until resolution.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Ethanol: (Major) Advise patients to avoid alcohol and alcohol-containing products while taking nilutamide. Alcohol intolerance has been reported in about 5% of patients treated with nilutamide. Facial flushing, malaise, and hypotension may occur following ingestion of nilutamide with alcohol. The mechanism of this interaction is not known. (Moderate) Alcohol intolerance has been reported in about 5 percent of patients treated with nilutamide. Facial flushing, malaise, and hypotension may occur following ingestion of nilutamide with alcohol. The mechanism of this interaction is not known. It is recommended that intake of alcohol-containing beverages be avoided by patients who experience this reaction while taking nilutamide.
Fosphenytoin: (Moderate) Nilutamide inhibits the activity of hepatic cytochrome P450 isoenzymes and may reduce the metabolism of drugs metabolized by these enzymes, such as fosphenytoin. The dosage of fosphenytoin may need to be modified if administered concomitantly with nilutamide.
Phenytoin: (Moderate) Nilutamide inhibits the activity of hepatic cytochrome P450 isoenzymes and may reduce the metabolism of drugs metabolized by these enzymes including phenytoin.
Theophylline, Aminophylline: (Moderate) Nilutamide inhibits the activity of hepatic cytochrome P450 isoenzymes and may reduce the metabolism of drugs metabolized by these enzymes including aminophylline. (Moderate) Nilutamide inhibits the activity of hepatic cytochrome P450 isoenzymes and may reduce the metabolism of drugs metabolized by these enzymes including theophylline.
Warfarin: (Moderate) Nilutamide inhibits the activity of hepatic cytochrome P450 isoenzymes and may reduce the metabolism of drugs by these enzymes. Drugs with a low therapeutic margin, such as warfarin, could have a delayed elimination and corresponding increase in serum half-life. Warfarin dose may need to be modified if administered concomitantly with nilutamide.

Nilandron/Nilutamide Oral Tab: 150mg

300 mg PO/day.

300 mg PO/day.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Mechanism of Action: Nilutamide is a nonsteroidal antiandrogen that irreversibly binds to androgen receptors and inhibits androgen binding. It is an antagonist at cytoplasmic androgen receptors in the hypothalamus, pituitary, and the prostate and competes with 5-dihydrotestosterone (DHT) for binding at these receptors. Nilutamide does not interact with progestin or glucocorticoid receptors. Nilutamide is not suitable for inducing chemical castration since, by blocking the feedback mechanism for control of testosterone secretion, it causes increased testosterone concentrations.

Nilutamide is administered orally. After absorption, there is a detectable distribution phase. There is moderate binding to plasma proteins and low binding to erythrocytes. The binding is nonsaturable except in the case of alpha1-1-glycoprotein, which makes a minor contribution to the total concentration of proteins in the plasma. Nilutamide is extensively metabolized; five metabolites have been isolated. Two metabolites display an asymmetric center, due to oxidation of a methyl group, resulting in the formation of D- and L-isomers. One of the metabolites was shown, in vitro, to possess 25—50% of the pharmacological activity of the parent drug, and the D-isomer of the active metabolite showed equal or greater potency compared to the L-isomer. However, the pharmacokinetics and the pharmacodynamics of the metabolites have not been fully investigated. With multiple dosing, enzyme inhibition may occur. Approximately 62% of a single orally administered dose is eliminated in the urine during the first 120 hours; less than 2% of the dose is excreted unchanged. Fecal elimination is minor, ranging from 1.4% to 7% of the dose after 4—5 days. The mean elimination half-life of nilutamide ranged from 38 to 59 hours with most values between 41 and 49 hours. The elimination of at least one metabolite ranges 59—126 hours.

Following oral dosing in patients with metastatic prostate cancer, nitulamide is rapidly and completely absorbed and yields high and persistent plasma concentrations.

Nilutamide is not indicated for use in females; it should not be used in women, especially for non-serious or non-life threatening conditions. It is not known if nilutamide may cause fetal harm or affect reproductive capacity if administered to a pregnant woman; it should only be given during pregnancy if clearly needed.