New label information to advise that GnRH agonists for prostate cancer could increase risk of diabetes and cardiovascular diseases

November 16, 2010

FDA is asking the manufacturers of gonadotropin-releasing hormone agonists to add new safety information to the Warnings and Precautions section of the drugs? labels about an increased risk of diabetes and certain cardiovascular diseases.

FDA is asking the manufacturers of gonadotropin-releasing hormone (GnRH) agonists to add new safety information to the Warnings and Precautions section of the drugs’ labels. The new information advises patients about an increased risk of diabetes and certain cardiovascular diseases in men taking the medications for the treatment of prostate cancer.

GnRH agonists are sold under the brand names Lupron (leupolide acetate); Zoladex (goserelin acetate); Trelstar (triptorelin pamoate for injectable suspension); and Eligard (leupolide acetate). Another brand, Viadur (leupolide acetate), was discontinued in 2008. Generic products also are available.

The decision to add the safety information is based on FDA’s review of several published studies and a Science Advisory described in its May 2010 Ongoing Safety Review of GnRH Agonists both of which indicated the possible increased risk of diabetes and certain cardiovascular diseases. In the review, the agency said that a preliminary and ongoing analysis found that patients receiving GnRH agonists were at a small increased risk for diabetes, heart attack, stroke, and sudden death.

FDA noted that a number of studies published during the past several years have shown a suspected link between GnRH agonists and serious comorbidities. In February, a joint advisory issued by the American Heart Association, the American Cancer Society, and the American Urological Association stated that “there may be a relationship” between androgen-deprivation therapy for prostate cancer and cardiovascular risk.

FDA advises physicians to suggest that patients receiving treatment with GnRH agonists undergo periodic monitoring of blood glucose and/or glycosylated hemoglobin. Increased blood glucose levels may represent the development of diabetes or worsening of blood glucose control in patients with diabetes. Physicians also should monitor patients for signs and symptoms suggestive of development of cardiovascular disease and manage according to current clinical practice.

Prostate cancer is the second most common type of cancer among men in the United States, behind skin cancer, and usually occurs in older men. This year an estimated 217,730 new cases of prostate cancer will be diagnosed and about 32,050 men will die from the disease, according to National Center for Health Statistics and the National Cancer Institute.