Anandron

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Anandron uses


DESCRIPTION

Anandron® tablets contain Anandron, a nonsteroidal, orally active antiandrogen having the chemical name 5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]-2,4-imidazolidinedione with the following structural formula:

Anandron is a microcrystalline, white to practically white powder with a molecular weight of 317.25.

Its molecular formula is C12H10F3N3O4.

It is freely soluble in ethyl acetate, acetone, chloroform, ethyl alcohol, dichloromethane, and methanol. It is slightly soluble in water [<0.1% W/V at 25°C (77°F)]. It melts between 153°C and 156°C (307.4°F and 312.8°F).

Each Anandron tablet contains 150 mg of Anandron. Other ingredients in Anandron tablets are corn starch, lactose, povidone, docusate sodium, magnesium stearate, and talc.

Chemical Structure

CLINICAL PHARMACOLOGY

Mechanism of Action

Prostate cancer is known to be androgen sensitive and responds to androgen ablation. In animal studies, Anandron has demonstrated antiandrogenic activity without other hormonal effects. In vitro, Anandron blocks the effects of testosterone at the androgen receptor level. In vivo, Anandron interacts with the androgen receptor and prevents the normal androgenic response.

Pharmacokinetics

Absorption

Analysis of blood, urine, and feces samples following a single oral 150-mg dose of [14C]-nilutamide in patients with metastatic prostate cancer showed that the drug is rapidly and completely absorbed and that it yields high and persistent plasma concentrations.

Distribution

After absorption of the drug, there is a detectable distribution phase. There is moderate binding of the drug to plasma proteins and low binding to erythrocytes. The binding is nonsaturable except in the case of alpha-1-glycoprotein, which makes a minor contribution to the total concentration of proteins in the plasma. The results of binding studies do not indicate any effects that would cause nonlinear pharmacokinetics.

Metabolism

The results of a human metabolism study using 14C-radiolabelled tablets show that Anandron is extensively metabolized and less than 2% of the drug is excreted unchanged in urine after 5 days. Five metabolites have been isolated from human urine. 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 to 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.

Elimination

The majority of orally administered [14C]-nilutamide is eliminated in the urine during the first 120 hours after a single 150-mg dose. Fecal elimination is negligible, ranging from 1.4% to 7% of the dose after 4 to 5 days. Excretion of radioactivity in urine likely continues beyond 5 days. The mean elimination half-life of Anandron determined in studies in which subjects received a single dose of 100–300 mg ranged from 38.0 to 59.1 hours with most values between 41 and 49 hours. The elimination of at least one metabolite is generally longer than that of unchanged Anandron (59–126 hours). During multiple dosing of 150 mg Anandron (given as 3 × 50 mg) twice a day, steady state was reached within 2 to 4 weeks for most patients, and mean steady state AUC0–12 was 110% higher than the AUC0– obtained from the first 150 mg dose. These data and in vitro metabolism data suggest that, upon multiple dosing, metabolic enzyme inhibition may occur for this drug.

Clinical Studies

Anandron through its antiandrogenic activity can complement surgical castration, which suppresses only testicular androgens. The effects of the combined therapy were studied in patients with previously untreated metastatic prostate cancer.

In a double-blind, randomized, multicenter study that enrolled 457 patients (225 treated with orchiectomy and Anandron, 232 treated with orchiectomy and placebo), the Anandron group showed a statistically significant benefit in time to progression and time to death. The results are summarized below.

Anandron PLACEBO
Median Survival (months) 27.3 23.6
Progression-Free Survival (months) 21.1 14.9
Complete or Partial Regression 41% 24%
Improvement in Bone Pain 54% 37%
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INDICATIONS AND USAGE

Metastatic Prostate Cancer

Anandron tablets are indicated for use in combination with surgical castration for the treatment of metastatic prostate cancer (Stage D2).

For maximum benefit, Anandron treatment must begin on the same day as or on the day after surgical castration.

CONTRAINDICATIONS

Anandron tablets are contraindicated:

WARNINGS

Interstitial Pneumonitis

Interstitial pneumonitis has been reported in 2% of patients in controlled clinical trials in patients exposed to Anandron. A small study in Japanese subjects showed that 8 of 47 patients developed 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. X-rays showed interstitial or alveolo-interstitial changes, and pulmonary function tests revealed a restrictive pattern with decreased DLco. Most cases occurred within the first 3 months of treatment with Anandron, and most reversed with discontinuation of therapy. A routine chest X-ray should be performed prior to initiating treatment with Anandron. Baseline pulmonary function tests may be considered. Patients should be instructed to report any new or worsening shortness of breath that they experience while on Anandron. If symptoms occur, Anandron should be immediately discontinued until it can be determined if the symptoms are drug related.

Hepatitis

Rare cases of death or hospitalization due to severe liver injury have been reported post-marketing in association with the use of Anandron. Hepatotoxicity in these reports generally occurred within the first 3 to 4 months of treatment. Hepatitis or marked increases in liver enzymes leading to drug discontinuation occurred in 1% of Anandron patients in controlled clinical trials.

Serum transaminase levels should be measured prior to starting treatment with Anandron, at regular intervals for the first 4 months of treatment, and periodically thereafter. Liver function tests should also be obtained at the first sign or symptom suggestive of liver dysfunction, e.g. nausea, vomiting, abdominal pain, fatigue, anorexia, "flu-like" symptoms, dark urine, jaundice, or right upper quadrant tenderness. If at any time, a patient has jaundice, or their ALT rises above 2 times the upper limit of normal, Anandron should be immediately discontinued with close followup of liver function tests until resolution.

Use in Women

Anandron has no indication for women, and should not be used in this population, particularly for non-serious or non-life threatening conditions.

Other

Foreign postmarketing surveillance has revealed isolated cases of aplastic anemia in which a causal relationship with Anandron could not be ascertained.

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PRECAUTIONS

General

Antiandrogen Withdrawal Syndrome

Patients whose disease progresses while being treated with an antiandrogen may experience clinical improvement with discontinuation of the antiandrogen.

Information For Patients

Patients should be informed that Anandron tablets should be started on the day of, or on the day after, surgical castration. They should also be informed that they should not interrupt their dosing of Anandron or stop taking this medication without consulting their physician.

Because of the possibility of interstitial pneumonitis, patients should also be told to report immediately any dyspnea or aggravation of pre-existing dyspnea.

Because of the possibility of hepatitis, patients should be told to consult with their physician should nausea, vomiting, abdominal pain, or jaundice occur.

Because of the possibility of an intolerance to alcohol following ingestion of Anandron, it is recommended that intake of alcoholic beverages be avoided by patients who experience this reaction. This effect has been reported in about 5% of patients treated with Anandron.

In clinical trials, 13% to 57% of patients receiving Anandron reported a delay in adaptation to dark, ranging from seconds to a few minutes, when passing from a lighted area to a dark area. This effect sometimes does not abate as drug treatment is continued. Patients who experience this effect should be cautioned about driving at night or through tunnels. This effect can be alleviated by the wearing of tinted glasses.

Drug Interactions

In vitro, Anandron has been shown to inhibit the activity of liver cytochrome P-450 isoenzymes and, therefore, may reduce the metabolism of compounds requiring these systems.

Consequently, drugs with a low therapeutic margin, such as vitamin K antagonists, phenytoin, and theophylline, could have a delayed elimination and increases in their serum half-life leading to a toxic level. The dosage of these drugs or others with a similar metabolism may need to be modified if they are administered concomitantly with Anandron. For example, when vitamin K antagonists are administered concomitantly with Anandron, prothrombin time should be carefully monitored and, if necessary, the dosage of vitamin K antagonists should be reduced.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Administration of Anandron to rats for 18 months at doses of 0, 5, 15, or 45 mg/kg/day produced benign Leydig cell tumors in 35% of the high-dose male rats. The increased incidence of Leydig cell tumors is secondary to elevated luteinizing hormone (LH) concentrations resulting from loss of feedback inhibition at the pituitary. Elevated LH and testosterone concentrations are not observed in castrated men receiving Anandron. Anandron had no effect on the incidence, size, or time of onset of any spontaneous tumor in rats.

Anandron displayed no mutagenic effects in a variety of in vitro and in vivo tests (Ames test, mouse micronucleus test, and two chromosomal aberration tests).

In reproduction studies in rats, Anandron had no effect on the reproductive function of males and females, and no lethal, teratogenic, or growth-suppressive effects on fetuses were found. The maximal dose at which Anandron did not affect reproductive function in either sex or have an effect on fetuses was estimated to be 45 mg/kg orally (AUC exposures in rats approximately 1–2 times human therapeutic AUC exposures).

Pregnancy

Pregnancy Category C; Animal reproduction studies have not been conducted with Anandron. It is also not known whether Anandron can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Anandron should be given to a pregnant woman only if clearly needed.

Pediatric Use

Safety and effectiveness in pediatric patients have not been determined.

Animal Pharmacology and Toxicology

Administration of Anandron to beagle dogs resulted in drug-related deaths at dose levels that produce AUC exposures in dogs much lower than the AUC exposures of men receiving the therapeutic doses of 150 and 300 mg/day. Nilutamide-induced toxicity in dogs was cumulative with progressively lower doses producing death when given for longer durations. Anandron given to dogs at 60 mg/kg/day (1–2 times human AUC exposure) for 1 month produced 100% mortality. Administration of 20 and 30 mg/kg/day Anandron (1/2–1 times human AUC exposure) for 6 months resulted in 20% and 70% mortality in treated dogs. Administration to dogs of 3, 6, and 12 mg/kg/day Anandron (1/10–1/2 human AUC exposure) for 1 year resulted in 8%, 33%, and 50% mortality, respectively. A "no-effect level" for nilutamide-induced mortality in dogs was not identified. Pathology data from the one-year oral toxicity study suggest that the deaths in dogs were secondary to liver toxicity. Marked-to-massive hepatocellular swelling and vacuolization were observed in affected dogs. Liver toxicity in dogs was not consistently associated with elevations of liver enzymes.

Administration of Anandron to rats at a dose level of 45 mg/kg/day (AUC exposure in rats 1–2 times human therapeutic AUC exposures) for 18 months increased the incidence of lung pathology (granulomatous inflammation and chronic alveolitis).

The hepatic and pulmonary adverse effects observed in nilutamide-treated animals and men are similar to effects observed with another nitroaromatic compound, nitrofurantoin. Anandron and nitrofurantoin are both metabolized in vitro to nitroanion free-radicals by microsomal NADPH-cytochrome P450 reductase in the lungs and liver of rats and humans.

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ADVERSE REACTIONS

The following adverse experiences were reported during a multicenter clinical trial comparing Anandron + surgical castration versus placebo + surgical castration. The most frequently reported (greater than 5%) adverse experiences during treatment with Anandron tablets in combination with surgical castration are listed below. For comparison, adverse experiences seen with surgical castration and placebo are also listed.

Adverse Experience Anandron

+

surgical

castration

(N=225)

% All

Placebo

+

surgical

castration

(N=232)

% All

Cardiovascular System
Hypertension 5.3 2.6
Digestive System
Nausea 9.8 6.0
Constipation 7.1 3.9
Endocrine System
Hot flushes 28.4 22.4
Metabolic and Nutritional System
Increased AST 8.0 3.9
Increased ALT 7.6 4.3
Nervous System
Dizziness 7.1 3.4
Respiratory System
Dyspnea 6.2 7.3
Special Senses
Impaired adaptation to dark 12.9 1.3
Abnormal vision 6.7 1.7
Urogenital System
Urinary tract infection 8.0 9.1

The overall incidence of adverse experiences was 86% (194/225) for the Anandron group and 81% (188/232) for the placebo group.

The following adverse experiences were reported during a multicenter clinical trial comparing Anandron + leuprolide versus placebo + leuprolide. The most frequently reported (greater than 5%) adverse experiences during treatment with Anandron tablets in combination with leuprolide are listed below. For comparison, adverse experiences seen with leuprolide and placebo are also listed.

Adverse Experience Anandron

+

leuprolide

(N=209)

% All

Placebo

+

leuprolide

(N=202)

% All

Body as a Whole
Pain 26.8 27.7
Headache 13.9 10.4
Asthenia 19.1 20.8
Back pain 11.5 16.8
Abdominal pain 10.0 5.4
Chest pain 7.2 4.5
Flu syndrome 7.2 3.0
Fever 5.3 6.4
Cardiovascular System
Hypertension 9.1 9.9
Digestive System
Nausea 23.9 8.4
Constipation 19.6 16.8
Anorexia 11.0 6.4
Dyspepsia 6.7 4.5
Vomiting 5.7 4.0
Endocrine System
Hot flushes 66.5 59.4
Impotence 11.0 12.9
Libido decreased 11.0 4.5
Hemic and Lymphatic System
Anemia 7.2 6.4
Metabolic and Nutritional System
Increased AST 12.9 13.9
Peripheral edema 12.4 17.3
Increased ALT 9.1 8.9
Musculoskeletal System
Bone Pain 6.2 5.0
Nervous System
Insomnia 16.3 15.8
Dizziness 10.0 11.4
Depression 8.6 7.4
Hypesthesia 5.3 2.0
Respiratory System
Dyspnea 10.5 7.4
Upper respiratory infection 8.1 10.9
Pneumonia 5.3 3.5
Skin and Appendages
Sweating 6.2 3.0
Body hair loss 5.7 0.5
Dry skin 5.3 2.5
Rash 5.3 4.0
Special Senses
Impaired adaptation to dark 56.9 5.4
Chromatopsia 8.6 0.0
Impaired adaptation to light 7.7 1.0
Abnormal vision 6.2 4.5
Urogenital System
Testicular atrophy 16.3 12.4
Gynecomastia 10.5 11.9
Urinary tract infection 8.6 21.3
Hematuria 8.1 7.9
Urinary tract disorder 7.2 10.4
Nocturia 6.7 6.4

The overall incidence of adverse experiences is 99.5% (208/209) for the Anandron group and 98.5% (199/202) for the placebo group.

Some frequently occurring adverse experiences, for example hot flushes, impotence, and decreased libido, are known to be associated with low serum androgen levels and known to occur with medical or surgical castration alone. Notable was the higher incidence of visual disturbances (variously described as impaired adaptation to darkness, abnormal vision, and colored vision), which led to treatment discontinuation in 1% to 2% of patients.

Interstitial pneumonitis occurred in one (<1%) patient receiving Anandron in combination with surgical castration and in seven patients (3%) receiving Anandron in combination with leuprolide and one patient receiving placebo in combination with leuprolide. Overall, it has been reported in 2% of patients receiving Anandron. This included a report of interstitial pneumonitis in 8 of 47 patients (17%) in a small study performed in Japan.

In addition, the following adverse experiences were reported in 2 to 5% of patients treated with Anandron in combination with leuprolide or orchiectomy.

Body as a Whole: Malaise (2%).

Cardiovascular System: Angina (2%), heart failure (3%), syncope (2%).

Digestive System: Diarrhea (2%), gastrointestinal disorder (2%), gastrointestinal hemorrhage (2%), melena (2%).

Metabolic and Nutritional System: Alcohol intolerance (5%), edema (2%), weight loss (2%).

Musculoskeletal System: Arthritis (2%).

Nervous System: Dry mouth (2%), nervousness (2%), paresthesia (3%).

Respiratory System: Cough increased (2%), interstitial lung disease (2%), lung disorder (4%), rhinitis (2%).

Skin and Appendages: Pruritus (2%).

Special Senses: Cataract (2%), photophobia (2%).

Laboratory Values: Haptoglobin increased (2%), leukopenia (3%), alkaline phosphatase increased (3%), BUN increased (2%), creatinine increased (2%), hyperglycemia (4%).

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OVERDOSAGE

One case of massive overdosage has been published. A 79-year-old man attempted suicide by ingesting 13 g of Anandron (i.e., 43 times the maximum recommended dose). Despite immediate gastric lavage and oral administration of activated charcoal, plasma Anandron levels peaked at 6 times the normal range 2 hours after ingestion. There were no clinical signs or symptoms or changes in parameters such as transaminases or chest X-ray. Maintenance treatment (150 mg/day) was resumed 30 days later.

In repeated-dose tolerance studies, doses of 600 mg/day and 900 mg/day were administered to 9 and 4 patients, respectively. The ingestion of these doses was associated with gastrointestinal disorders, including nausea and vomiting, malaise, headache, and dizziness. In addition, a transient elevation in hepatic enzyme levels was noted in one patient.

Since Anandron is protein bound, dialysis may not be useful as treatment for overdose. As in the management of overdosage with any drug, it should be borne in mind that multiple agents may have been taken. If vomiting does not occur spontaneously, it should be induced if the patient is alert. General supportive care, including frequent monitoring of the vital signs and close observation of the patient, is indicated.

DOSAGE AND ADMINISTRATION

The recommended dosage is 300 mg once a day for 30 days, followed thereafter by 150 mg once a day. Anandron tablets can be taken with or without food.

HOW SUPPLIED

Anandron 150 mg tablets are supplied in boxes of 30 tablets. Each box contains 3 child-resistant, PVC, aluminum foil-backed blisters of 10 tablets (NDC 0088-1111-14). Each white, biconvex, cylindrical (10 mm in diameter) tablet has a triangular logo on one side and an internal reference number (168D) on the other.

Store at 25°C (77°F); excursions permitted between 15–30°C (59–86°F). Protect from light.

Revised June 2006

sanofi-aventis U.S. LLC

Bridgewater, NJ 08807

Country of Origin: France

© 2006 sanofi-aventis U.S. LLC

Anandron pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Anandron available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Anandron destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Anandron Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Anandron pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."NILANDRON (NILUTAMIDE) TABLET [SANOFI-AVENTIS U.S. LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."NILUTAMIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "nilutamide". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Anandron?

Depending on the reaction of the Anandron after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Anandron not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Anandron addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Anandron, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Anandron consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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