Proscar is a product of Merck & Co

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first.

Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in over 20 therapeutic categories.

Merck & Co. aims at helping to improve the health and well-being of people everywhere by discovering, developing and bringing to market breakthrough medicines. Their priorities are focused on turning cutting-edge science into breakthrough medicines that address significant unmet needs, and thus have the potential to become important medical advances.

2.PROSCAR FACTS

In the body, the hormone testosterone is converted to a more active form, dihydrotestosterone (DHT), by 5-alpha reductase. Proscar blocks the action of 5-alpha reductase, and therefore prevents the activation of testosterone.

Proscar is used in benign prostatic hyperplasia (BPH) in low doses, and in prostate cancer in higher doses. Additionally, it is registered in many countries for male-pattern baldness.

Drug trade names include Propecia® and Proscar® both products of Merck & Co. 

3.ABOUT PROSCAR 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. Proscar and 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.PROSCAR EFFECTIVENESS
When is Proscar best taken?

Absorption

In a study of 15 healthy young subjects, the mean bioavailability of Proscar tablets was 63% (range 34-108%), based on the ratio of area under the curve (AUC) relative to an intravenous (IV) reference dose. Maximum Proscar plasma concentration averaged 37 ng/mL (range, 27-49 ng/mL) and was reached 1-2 hours post Proscar dose. Bioavailability of Proscar was not affected by food.

Distribution

Mean steady-state volume of distribution was 76 liters. Approximately 90% of circulating Proscar is bound to plasma proteins. There is a slow accumulation phase for Proscar after multiple dosing. After dosing with 5 mg/day of Proscar for 17 days, plasma concentrations of Proscar were 47 and 54% higher than after the first dose in men 45-60 years old (n=12) and >/=70 years old (n=12), respectively. Mean trough concentrations after 17 days of dosing were 6.2 ng/mL (range, 2.4-9.8 ng/mL) and 8.1 ng/mL (range, 1.8-19.7 ng/mL), respectively, in the two age groups. Although steady state was not reached in this study, mean trough plasma concentration in another study in patients with BPH (mean age, 65 years) receiving 5 mg/day was 9.4 ng/mL (range, 7.1-13.3 ng/mL; n=22) after over a year of dosing.

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

Metabolism

Proscar is extensively metabolized in the liver, primarily via the cytochrome P450 3A4 enzyme subfamily. Two metabolites, the t-butyl side chain monohydroxylated and monocarboxylic acid metabolites, have been identified that possess no more than 20% of the 5(alpha)-reductase inhibitory activity of finasteride.

Excretion

In healthy young subjects (n=15), mean plasma clearance of Proscar was 165 mL/min and mean elimination half-life in plasma was 6 hours (range, 3-16 hours). Following an oral Proscar dose of 14 C-finasteride in man (n=6), a mean of 39% (range, 32-46%) of the Proscar 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 Proscar 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 Proscar dosing was 15% higher in subjects >/= 70 years of age than in subjects 45-60 years of age (p=0.02).

5.PROSCAR EFFECTS ON SPECIAL POPULATION
How do different people react to Proscar?

Pediatric : Proscar pharmacokinetics have not been investigated in patients <18 years of age.

Gender: Proscar pharmacokinetics in women are not available.

Geriatric : No Proscar dosage adjustment is necessary in the elderly. Although the elimination rate of finasteride is decreased in the elderly, these findings are of no clinical significance.

Race : The effect of race on Proscar pharmacokinetics has not been studied.

6.PROSCAR EFFECTS ON MEDICAL CONDITIONS
How does Proscar affect your existing condition/ailment?

Renal Insufficiency : No Proscar dosage adjustment is necessary in patients with renal insufficiency. In patients with chronic renal impairment, with creatinine clearances ranging from 9.0 to 55 mL/min, AUC, maximum plasma concentration, half-life, and protein binding after a single dose of 14 C-finasteride were similar to values obtained in healthy volunteers. Urinary excretion of metabolites was decreased in patients with renal impairment. This decrease was associated with an increase in fecal excretion of metabolites. Plasma concentrations of metabolites were significantly higher in patients with renal impairment (based on a 60% increase in total radioactivity AUC). However, finasteride has been well tolerated in BPH patients with normal renal function receiving up to 80 mg/day for 12 weeks, where exposure of these patients to metabolites would presumably be much greater.

Hepatic Insufficiency: The effect of hepatic insufficiency on Proscar pharmacokinetics has not been studied. Caution should be used in the administration of Proscar in those patients with liver function abnormalities, as Proscar is metabolized extensively in the liver. 

7.OTHER/ALTERNATE USES OF PROSCAR
What else does Proscar treat?

Proscar is also used in the treatment of hair loss.

8.ADVERSE/SIDE EFFECTS of PROSCAR
What are the side effects of Proscar?

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

1524 patients treated with Proscar 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 Proscar 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 Proscar 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 Proscar 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 Proscar. 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 Proscar. 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 Proscar 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 Proscar 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 of Proscar have been reported in post-marketing experience:

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