Avodart™ (dutasteride) is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve urinary symptoms, reduce risk of acute urinary retention (AUR) and reduce the risk of the need for BPH-related surgery.

Avodart, a second-generation 5 alpha-reductase inhibitor (5 A-RI), is the first and only medicine to inhibit both the type 1 and type 2 enzymes responsible for the conversion of testosterone to DHT (dihydrotestosterone), the primary cause of prostate growth. Avodart’s dual inhibition decreases levels of DHT by 90 percent at two weeks and 93 percent at two years. By reducing DHT levels, Avodart reduces the size of an enlarged prostate.

Avodart will become available by prescription in the United States in December 2002.

Avodart: The First Dual-Acting 5 Alpha-Reductase Inhibitor for BPH

Rationale

BPH is one of the most common health problems in older men.1

BPH is a progressive condition in which the prostate gland surrounding the urethra enlarges. As it grows, the enlarged prostate obstructs the urethra, the tube through which urine flows, causing urinary difficulties. An enlarged prostate can continue to increase in size and in severe cases lead to acute urinary retention (AUR; a sudden and complete inability to urinate) and the need for BPH-related surgery.1

DHT (dihydrotestosterone) is the male hormone primarily responsible for the initial development and subsequent enlargement of the prostate gland.

Benefits

Avodart, a second-generation 5 alpha-reductase inhibitor, is the first and only medicine to inhibit both the type 1 and type 2 enzymes responsible for the conversion of the male hormone testosterone to DHT.

Avodart's dual inhibition decreases levels of DHT by 90 percent at two weeks and 93 percent at two years. By reducing DHT levels, Avodart reduces the size of an enlarged prostate.

Avodart also improves urinary symptoms and reduces the risk of AUR and the need for BPH-related surgery, two potential long-term serious consequences of BPH.

Clinical Highlights

Avodart was investigated in three large, well-controlled multi-center studies involving 4,325 men aged 50 and above with a serum PSA level = 1.5 ng/mL and < 10 ng/mL, and BPH diagnosed by medical history and physical examination, including enlarged prostate (greater than or equal to 30 cc) and BPH symptoms that were moderate to severe according to the American Urological Association Symptom Index.

Data from these two-year clinical trials demonstrated that treatment with Avodart (0.5 mg once daily) reduced the risk of both AUR and BPH-related surgical intervention relative to placebo, improved BPH-related symptoms, decreased prostate volume, and increased maximum urinary flow rates.

Clinical trials of Avodart showed that it was generally well tolerated. Most side effects were mild or moderate and generally went away while on treatment in both the Avodart and placebo groups.

Drug-related side effects during the first six months were as follows: impotence (4.7 percent vs. 1.7 percent for placebo), decreased libido (3 percent vs. 1.4 percent), breast tenderness and breast enlargement (gynecomastia; 0.5 percent vs. 0.2 percent) and ejaculation disorders (1.4 percent vs. 0.5 percent). The incidence of most drug-related sexual side effects decreased with duration of treatment. The incidence of drug-related breast tenderness and breast enlargement remained constant over the treatment period. Ejaculate volume may be decreased in some patients with continued treatment. This decrease did not appear to interfere with normal sexual function.

- Avodart should not be used in women and children. Women who are pregnant or may become pregnant should not handle Avodart because of possibility of absorption of Avodart and subsequent potential risk to a male fetus.

- Men treated with Avodart should not donate blood until at least six months after their final dose to prevent giving Avodart to a pregnant woman through a blood transfusion. Men with an allergic reaction to Avodart or its ingredients should not take it. Men with liver disease should talk to their doctor before taking Avodart.

- Avodart will reduce the amount of PSA measured in the blood. A physician will be aware of this effect and can still use PSA to detect prostate cancer.

- Although improvement in urinary symptoms was seen in some patients by three months, a therapeutic trial of at least six months is usually necessary to assess whether a beneficial response in symptom relief is achieved with Avodart.

The recommended dose of Avodart is a 0.5 mg soft gelatin capsule taken once daily.

Indication

Avodart is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve urinary symptoms, reduce risk of acute urinary retention and reduce the risk of the need for BPH-related surgery.

Avodart will be available for prescription in December 2002.