1. AVODART HISTORY
How was Avodart discovered?

Avodart is a product of GlaxoSmithKline. 

GlaxoSmithKline is a world-leading, research-based pharmaceutical company operating in more than 100 countries and employing more than 100,000 people worldwide. GlaxoSmithKline (GSK) is a world leading research-based pharmaceutical company with a powerful combination of skills and resources that provides a platform for delivering strong growth in today's rapidly changing healthcare environment. Headquartered in the UK and with operations based in the US, the new company is one of the industry leaders, with an estimated seven per cent of the world's pharmaceutical market.

GSK has more than 20 research and development (R&D) facilities around the world, with an annual R&D budget of around $7 billion and more than 16,000 people employed in R&D.

GSK also has leadership in four major therapeutic areas - anti-infectives, central nervous system (CNS), respiratory and gastro-intestinal/metabolic. In addition, it is a leader in the important area of vaccines and has a growing portfolio of oncology products.

GSK also has a Consumer Healthcare portfolio comprising over-the-counter (OTC) medicines, oral care products and nutritional healthcare drinks, all of which are among the market leaders.

GSK's R&D is based at 24 sites in seven countries. 

Note: World-drugs.net sells generic version of Avodart

2.AVODART FACTS

Avodart works by inhibiting the action of a compound in the body called 5-alpha reductase. This compound is called an enzyme, and is responsible for converting the male hormone testosterone into dihydrotestosterone (DHT), which is a more active form of testosterone.

The enlargement of the prostate gland, (known medically as Benign prostatic hyperplasia), which often occurs in men with advancing age, is dependant upon testosterone being converted to DHT within the prostate gland. In the absence of DHT the prostate gland shrinks. By decreasing the amount of testosterone that is converted into DHT, Avodart therefore helps to shrink the prostate gland.

Avodart is used to relieve moderate to severe symptoms of BPH and to reduce the risk of developing a complete inability to pass urine (acute urinary retention) that may require surgery. 

3.ABOUT AVODART MEDICATION

What is benign prostatic hyperplasia?
Benign prostatic hyperplasia (BPH) is a condition that affects the prostate gland in men.

The prostate is a gland found between the bladder (where urine is stored) and the urethra (the tube urine passes through). As men age, the prostate gland slowly grows bigger (or enlarges). As the prostate gets bigger, it may press on the urethra and cause the flow of urine to be slower and less forceful.

"Benign" means the enlargement isn't caused by cancer or infection. "Hyperplasia" means enlargement.

What are the symptoms of BPH?
Most symptoms of BPH start gradually. One symptom is the need to get up more often at night to urinate. Another symptom is the need to empty the bladder often during the day. Other symptoms include difficulty in starting the urine flow and dribbling after urination ends. The size and strength of the urine stream may decrease.

These symptoms can be caused by other things besides BPH. They may be signs of more serious diseases, such as a bladder infection or bladder cancer. Tell your doctor if you have any of these symptoms, so he or she can decide which tests to use to find the possible cause.

How will my doctor know if I have BPH?
After your doctor takes a complete history of your symptoms, a rectal exam is the next step. This exam allows your doctor to actually feel the size of the prostate gland.

It might not be possible for your doctor to be sure that your prostate problem is benign just by taking a history and performing a physical exam. Your doctor might need to look at a sample of your urine for signs of infection. Your doctor may also do a blood test. An ultrasound exam or a biopsy of the prostate may help your doctor make the diagnosis.

How will my doctor treat my BPH?
Once your doctor is sure that your symptoms are caused by benign growth of the prostate gland, treatment can be recommended. However, your doctor may suggest that you wait to see if your symptoms get better because sometimes-mild symptoms get better on their own. If your symptoms get worse, your doctor may suggest another treatment option.

Surgery is considered the most effective treatment and is used in men with strong symptoms. This is also the best way to diagnose and cure early cancer of the prostate. Surgery is usually done through the urethra, leaving no scars. Surgery does have risks, such as bleeding, infection or impotence. These risks are generally small.

Are there any drugs I can take?
Drug treatments are available. Finasteride and Avodart (dutasteride) blocks a natural hormone that makes the prostate enlarge, but it does not help all patients. The side effects of finasteride are rare and mild, but they usually have to do with sexual function. They go away when the medicine is stopped. The prostate will enlarge again when the medicine is stopped, so another treatment may have to be tried.

Another kind of medicine, called alpha blockers, also can help the symptoms of BPH. Some of these drugs are terazosin, doxazosin, tamsulosin and alfuzosin . Alpha blockers have been used for a long time to treat high blood pressure, but they can also help the symptoms of BPH, even in men with normal blood pressure. These medicines may not work in all men. The side effects of alpha blockers are mild and go away if you stop taking the medicine. The side effects include dizziness, fatigue and lightheadedness. 

4.AVODART EFFECTIVENESS
When is Avodart best taken?)

Absorption
In a study of 15 healthy young subjects, the mean bioavailability of Avodart tablets was 63% (range 34-108%). Maximum Avodart plasma concentration averaged 37 ng/mL (range, 27-49 ng/mL) and was reached 1-2 hours post Avodart dose. Bioavailability of Avodart was not affected by food.

Distribution
Mean steady-state volume of distribution was 76 liters. Approximately 90% of circulating Avodart is bound to plasma proteins. There is a slow accumulation phase for Avodart after multiple Avodart dosing.

Avodart has been shown to cross the blood brain barrier but does not appear to distribute preferentially to the CSF.

Metabolism
Avodart is extensively metabolized in the liver, primarily via the cytochrome P450 3A4 enzyme subfamily.

Excretion
In healthy young subjects (n=15), mean plasma clearance of Avodart was 165 mL/min and mean elimination half-life in plasma was 6 hours (range, 3-16 hours). Following an oral dose of 14 C-finasteride in man (n=6), a mean of 39% (range, 32-46%) of the dose was excreted in the urine in the form of metabolites; 57% (range, 51-64%) was excreted in the feces.

The mean terminal half-life of Avodart in subjects >/= 70 years of age was approximately 8 hours (range, 6-15 hours; n=12), compared with 6 hours (range, 4-12 hours; n=12) in subjects 45-60 years of age. As a result, mean AUC (0-24 hr) after 17 days of dosing was 15% higher in subjects >/= 70 years of age than in subjects 45-60 years of age (p=0.02). 

5.AVODART EFFECTS ON SPECIAL POPULATION
(How do different people react to Avodart?)

Pregnancy
Avodart is for use by men only, therefore information about its use by pregnant or breastfeeding women are not applicable. However, Avodart may pass into semen, and for this reason men whose partner is or may be pregnant should use a barrier form of contraception such as a condom during sex, to avoid any possible risks to a developing foetus.

Avodart can pass through the skin. Therefore, women who are pregnant or may be pregnant should NOT touch Avodart since it can pass through the skin and may cause birth defects in a male baby.

Children
Avodart should not be used in children.

Elderly patients
Avodart has been tested and has not been shown to cause different side effects or problems in older people than it does in younger adults.

6.AVODART EFFECTS ON MEDICAL CONDITIONS
(How does Avodart affect your existing condition/ailment?

Avodart should not be used if you suffer from mild to moderately decreased liver function.

Avodart should not be used if you are allergic to one or any of its ingredients.

If you feel you have experienced an allergic reaction, stop using Avodart and inform your doctor or pharmacist immediately. 

7.OTHER/ALTERNATE USES OF AVODART
(What else does Avodart treat?)

Avodart is also used in the treatment of hair loss.

8.ADVERSE/SIDE EFFECTS of AVODART
What are the side effects of Avodart?

Avodart is generally well tolerated. Avodart adverse reactions usually have been mild and transient.

1524 patients treated with Avodart and 1516 patients treated with placebo were evaluated for safety over a period of 4 years. The most frequently reported adverse reactions were related to sexual function. 3.7% (57 patients) treated with Avodart and 2.1% (32 patients) treated with placebo discontinued therapy as a result of adverse reactions related to sexual function, which are the most frequently reported adverse reactions.

The table below presents the only clinical adverse reactions considered possibly, probably or definitely drug related by the investigator, for which the incidence on Avodart was 1% and greater than placebo over the 4 years of the study. In years 2-4 of the study, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder.

 

 

 

 

 

 

 

 

 

 

 

 

 

Medical Therapy of Prostatic Symptoms (MTOPS) Study
The individual adverse effects which occurred more frequently in the combination group compared to either drug alone were: asthenia, postural hypotension, peripheral edema, dizziness, decreased libido, rhinitis, abnormal ejaculation, impotence and abnormal sexual function. Of these, the incidence of abnormal ejaculation in patients receiving combination therapy was comparable to the sum of the incidences of this adverse experience reported for the two monotherapies.

Combination therapy with Avodart and doxazosin was associated with no new clinical adverse experience.

Four patients in MTOPS reported the adverse experience breast cancer. Three of these patients were on finasteride only and one was on combination therapy.

The MTOPS Study was not specifically designed to make statistical comparisons between groups for reported adverse experiences. In addition, direct comparisons of safety data between the MTOPS study and previous studies of the single agents may not be appropriate based upon differences in patient population, dosage or dose regimen, and other procedural and study design elements.

Long-Term Data

There is no evidence of increased adverse experiences with increased duration of treatment with Avodart. New reports of drug-related sexual adverse experiences decreased with duration of therapy.

During the 4- to 6-year placebo- and comparator-controlled MTOPS study that enrolled 3047 men, there were 4 cases of breast cancer in men treated with finasteride but no cases in men not treated with Avodart. During the 4-year, placebo-controlled study that enrolled 3040 men, there were 2 cases of breast cancer in placebo-treated men, but no cases were reported in men treated with finasteride. The relationship between long-term use of Avodart and male breast neoplasia is currently unknown.

In a 7-year placebo-controlled trial that enrolled 18,882 healthy men, 9060 had prostate needle biopsy data available for analysis. In the Avodart group, 280 (6.4%) men had prostate cancer with Gleason scores of 7-10 detected on needle biopsy vs. 237 (5.1%) men in the placebo group. Of the total cases of prostate cancer diagnosed in this study, approximately 98% were classified as intracapsular (stage T1 or T2). The clinical significance of these findings is unknown.

Post-Marketing Experience

The following additional adverse effects have been reported in post-marketing experience:

• hypersensitivity reactions, including pruritus, urticaria, and swelling of the lips and face
• testicular pain.