The FDA is informing physicians that the "Warnings and Precautions" section of package labels for the entire 5-alpha reductase inhibitor, or 5-ARI, class of drugs has been revised to include new safety information about the increased risk of high-grade prostate cancer associated with the medications.
"This risk appears to be low," the agency said in a June 9 safety announcement(www.fda.gov), "but health care professionals should be aware of this safety information, and weigh the known benefits against the potential risks when deciding to start or continue treatment with 5-ARIs in men."
About 5 million male patients received a prescription for a 5-ARI from 2002 to 2009, according to the FDA.
The labeling change affects the following drugs:
- finasteride, which is marketed as Propecia in 1-milligram strength and Proscar in 5-milligram strength;
- dutasteride, which as marketed as Avodart; and
- dutasteride in combination with tamsulosin, which is marketed as Jalyn.
Proscar, Avodart, and Jalyn are approved to treat symptoms of benign prostatic hyperplasia, or BPH. Proscar and Avodart also are approved to reduce the risk of urinary retention or surgery related to an enlarged prostate. Propecia is approved to treat male pattern hair loss.
The FDA made the labeling change based on its review of two large randomized, double-blind, controlled trials -- the Prostate Cancer Prevention Trial, or PCPT, and the Reduction by Dutasteride of Prostate Cancer Events, or REDUCE, trial. The two trials demonstrated an overall reduction in prostate cancer diagnoses with 5-milligram finasteride (a 26 percent reduction among treated men in the PCPT) and 0.5-milligram dutasteride (a 23 percent reduction among treated men in the REDUCE trial), respectively. Specifically, this reduction was due to a decreased incidence of lower risk forms of prostate cancer (Gleason Score, or GS, 6 or lower). However, both trials showed an increased incidence of high-grade prostate cancer (GS 8 or greater) among treated men versus those taking placebo (PCPT: 1.8 percent versus 1.1 percent; REDUCE trial: 1.0 percent versus 0.5 percent).
The agency issued the following information for health care professionals:
- Before initiating therapy with 5-ARIs, perform appropriate evaluation to rule out other urological conditions -- including prostate cancer -- that might mimic BPH.
- Be aware that treatment with 5-ARIs causes an approximate 50 percent reduction in prostate-specific antigen, or PSA, values within six months; however, individual patients receiving 5-ARIs may experience varying decreases in PSA values. Therefore, any confirmed increase in PSA while on a 5-ARI may signal the presence of prostate cancer and should be evaluated, even if that PSA is in the normal range of men not taking a 5-ARI.
- Know that 5-ARIs are not approved for the prevention of prostate cancer.
- Report any adverse events involving 5-ARIs to the FDA's MedWatch program(www.accessdata.fda.gov).