Men with benign prostatic hyperplasia (BPH) will soon have a therapeutic option that will reduce the risk of acute urinary retention and the need for BPH-related surgery, and improve the symptoms of BPH. On October 10, the FDA approved the supplemental New Drug Application (sNDA) for dutasteride (Avodart, GlaxoSmithKline) for the treatment of BPH in men with an enlarged prostate. Dutasteride will be available in pharmacies in December.
Men with benign prostatic hyperplasia (BPH) will soon have a therapeutic option that will reduce the risk of acute urinary retention and the need for BPH-related surgery while improving the symptoms of BPH.
Last month, the Food & Drug Administration approved the supplemental New Drug Application for dutasteride (Avodart, GlaxoSmithKline) for the treatment of BPH in men with an enlarged prostate. Dutasteride will be available in pharmacies in December.
As stated in the package insert (PI), the serum prostate specific antigen (PSA) will decrease by 20% within the first month of dutasteride therapy. The PSA value will be reduced by approximately 50% after six months of treatment, said Roehrborn.
The recommended dosage of dutasteride is one 0.5-mg softgel capsule taken daily by mouth, with or without food. Dosage adjustment is not necessary in older patients or in those with renal impairment.
The FDA based its approval on the results of three multicenter studies involving 4,325 men age 50 years or older, who had a serum PSA value of > 1.5 ng/ml but < 10.0 ng/ml, as described in the PI. Those enrolled in the study had a diagnosis of BPH, based on their medical history and a physical examination. Study data indicated that treatment with du- tasteride reduced the risk of acute urinary retention and BPH-related surgery, improved BPH-related symptoms, decreased prostate volume, and increased maximum urinary flow rates.
Dutasteride originally received FDA approval in November 2001. According to Veronica Grosshandler, product communications manager for GlaxoSmithKline, the company delayed its launch of the product until approval of the sNDA in order to include the two-year treatment data in the PI. The manufacturer wanted to provide the additional data to help healthcare providers make better decisions about the use of dutasteride in appropriate patients, she explained.
Claus Roehrborn, M.D., professor and chairman, department of urology, University of Texas Southwestern Medical Center, said that dutasteride is the first and only compound to inhibit both the type 1 and type 2 isoforms of the 5-alpha-reductase enzyme, which converts testosterone to dihydrotestosterone (DHT). DHT is known to be the primary cause of prostate growth.
The PI states that dutasteride should be used with caution in men taking potent inhibitors of the cytochrome P-450 3A4 (CYP3A4) isoenzyme, including ritonavir (Norvir, Abbott), ketoconazole, verapamil, diltiazem, cimetidine, and ciprofloxacin (Cipro, Bayer). The drug should also be used with caution in those with hepatic impairment.
Roehrborn said that the adverse effects associated with dutasteride in clinical trials were mild and generally transient in nature. Sexual adverse effects included impotence, decreased libido, and ejaculation disorders, he said. The most common nonsexual adverse event was gynecomastia (including breast tenderness). The incidence of sexual adverse events decreased with duration of treatment, while the incidence of gynecomastia remained constant throughout treatment, he said. There was a decrease in ejaculate volume in some patients, he noted, but it did not appear to interfere with normal sexual functioning.
Dutasteride is contraindicated for use in women and children, said Roehrborn. According to the PI, dutasteride is classified as a pregnancy category X, because suppression of circulating levels of DHT may inhibit the development of the external genitalia of a male fetus.
Roehrborn and Grosshandler reported that GlaxoSmithKline will be conducting studies of dutasteride for the treatment of alopecia, and that the company is also interested in evaluating the use of the drug to reduce the risk of prostate cancer.
Charlotte LoBuono. New drug for enlarged prostate to hit pharmacies next month. Drug Topics 2002;22:22.