Merck & Co, Inc announced that the Food and Drug Administration (FDA) has approved changes to the prescribing information for Proscar (finasteride) based on a landmark National Institutes of Health (NIH) study. Now, Proscar administered in combination with the alpha-blocker doxazosin is indicated to reduce the risk of the symptoms of benign prostatic hyperplasia (BPH), or benign enlargement of the prostate, from progressing over time (a confirmed rise of four or more points in AUA symptom score).

Benign prostatic hyperplasia is a common condition that occurs in more than 50 per cent of men between the ages of 51 and 60 and up to 90 per cent of men over the age of 90. Benign prostatic hyperplasia can block the flow of urine through the urethra and may cause symptoms, such as slow urinary stream, straining to urinate, frequent urination, nighttime urination and an urgency to urinate.

The new indication is based on the Medical Therapy of Prostatic Symptoms (MTOPS) study published in December 2003 in The New England Journal of Medicine. In this 3,047-patient study, PROSCAR combined with doxazosin significantly reduced the risk of BPH symptoms progressing when compared to placebo and to either Proscar or doxazosin alone.

"Before now, I commonly treated men first diagnosed with BPH with an alpha-blocker, such as doxazosin. Today, for the first time, the FDA has approved combination therapy with finasteride and doxazosin," said Steven Kaplan, M.D, vice chairman, Department of Urology at Columbia University Medical Center, and MTOPS study investigator. "Finasteride when combined with doxazosin has been shown to reduce the risk of BPH symptoms getting worse. In my own practice, I plan to use more combination therapy to treat men with symptoms of BPH."

Long-term NIH study conducted at 17 medical centers MTOPS was a multi-center, double-blind, placebo-controlled study conducted and funded by the National Institute of Diabetes and Digestive and Kidney Diseases, a part of the NIH. In the four- to six-year study (average five years), 3,047 randomized men with moderate to severe BPH symptoms either took placebo (n=737), PROSCAR 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756) or a combination of the two active treatments (n=786).

The primary endpoint of the study was a composite measure of the first occurrence of any of the five following outcomes: a confirmed rise of four or more points from baseline in the American Urological Association (AUA) symptom score [the AUA symptom score scale ranges from 0 (no symptoms) to 35 (severe symptoms)], acute urinary retention, renal insufficiency due to BPH, recurrent urinary tract infections or incontinence. The most common event in the composite primary endpoint was an increase in AUA symptom score of four points or greater above baseline, referred to as symptom score progression. This accounted for 274 of the 351 events, or 78 per cent, of the primary endpoint events.

Compared to placebo, treatment with combination therapy, Proscar alone and doxazosin alone significantly reduced the risk of experiencing one of the five outcome events. Combination therapy also resulted in a significant reduction in the risk of the composite primary endpoint compared to treatment with Proscar alone or doxazosin alone.

Combination therapy with Proscar and doxazosin significantly reduced the risk of the primary endpoint by 67 per cent compared to placebo [from 17.4 per cent with placebo (128 events) to 6.2 per cent with combination therapy (49 events), for an absolute risk reduction of 11.2 per cent]. Combination therapy also significantly reduced the risk by 49 per cent compared to Proscar alone [from 11.6 per cent with Proscar (89 events) to 6.2 per cent with combination therapy (49 events), for an absolute risk reduction of 5.4 per cent] and by 46 per cent compared to doxazosin alone [from 11.2 per cent with doxazosin (85 events) to 6.2 per cent with combination therapy (49 events), for an absolute risk reduction of 5.0 per cent].

Proscar with doxazosin reduced risk of symptom score progression by 64 per cent.