The FDA is requiring manufacturers of gonadotropin-releasing hormone, or GnRH, agonists to update their products' labeling(www.fda.gov) with new safety information because the medications, which are used primarily to treat advanced prostate cancer, have been linked to an increased risk of developing diabetes and cardiovascular disease.
The following medications are affected by the label changes:
- leuprolide acetate, which is marketed as Eligard, Lupron, Lupron Depot and Viadur;
- goserelin acetate, which is marketed as Zoladex;
- triptorelin pamoate, which is marketed as Trelstar; and
- histrelin acetate, which is marketed as Vantas.
In addition to prostate cancer, several of these agents are indicated for the treatment of breast cancer, central precocious puberty and such estrogen-mediated conditions as endometriosis and uterine fibroids. Some also are used in assisted reproduction.
One additional GnRH agonist, nafarel acetate, which is marketed as Synarel, is indicated solely to treat endometriosis in women and central precocious puberty in children.
The FDA announced in May that it was conducting a safety review of GnRH agonists after data from six studies raised concerns about a possible small increased risk for diabetes and/or certain cardiovascular events in patients undergoing androgen deprivation therapy with these agents. FDA officials said at the time, however, that various study design limitations made it difficult to confirm a cause-and-effect relationship.
In a safety announcement(www.fda.gov) released Oct. 20, the agency stated that the majority of studies reviewed by the agency did, in fact, demonstrate small but statistically significant increased risks for diabetes and/or cardiovascular events in patients receiving these medications.
Therefore, the agency has issued the following recommendations for physicians.
- Carefully weigh the known benefits and risks of GnRH agonists when determining appropriate treatment for prostate cancer.
- Monitor blood glucose and/or glycosylated hemoglobin periodically in patients receiving GnRH agonists.
- Monitor patients for signs and symptoms that suggest the development of cardiovascular disease.
- Ensure that cardiovascular risk factors, such as cigarette smoking, high blood pressure, high cholesterol, high blood sugar and excessive weight are managed according to current clinical practice.
- Report adverse events to the FDA's MedWatch program(www.accessdata.fda.gov).
The FDA also advised patients to inform their physicians before receiving GnRH agonists if they have diabetes; heart disease; a history of heart attack or stroke; or any cardiovascular risk factors, such as high blood pressure, high cholesterol or cigarette smoking.