FDA, manufacturers agree to update ED drug labels

August 1, 2005

Rockville, MD--After discussion with the FDA, manufacturers of three drugs used to treat erectile dysfunction have agreed to revise drug labels and physician and patient information to include stronger warnings about possible vision loss. The new labeling became effective immediately on its approval on July 8, 2005.

Rockville, MD-After discussion with the FDA, manufacturers of three drugs used to treat erectile dysfunction have agreed to revise drug labels and physician and patient information to include stronger warnings about possible vision loss. The new labeling became effective immediately on its approval on July 8, 2005.

Links to the revised text for the currently marketed phosphodiesterase type-5 inhibitors-Pfizer's sildenafil citrate (Viagra), Lilly-ICOS' tadalafil (Cialis), and Schering-Plough/GlaxoSmithKline's vardenafil hydrochloride (Levitra)-are posted on the FDA Center for Drug Evaluation and Research web page; the revised labeling has been disseminated via FDA's MedWatch e-LIST notification system. In addition, the manufacturers have revised their web sites and customer relations phone lines accordingly.

The push for label revision sprang from a study published in the Journal of Neuro-Ophthalmology (2005; 25:9-13), reporting incidents of nonarteritic ischemic optic neuropathy (NAION) in seven patients occurring within 36 hours after taking sildenafil for ED. Eventually, 43 cases (38 in sildenafil users, four in tadalafil, and one in vardenafil) were reported to FDA.

While an FDA statement acknowledges that a causal relationship between use of these drugs and NAION has not been definitively established, it cautions physicians about prescribing PDE-5 inhibitors for patients with ED who may have high blood pressure, diabetes, or other cardiovascular conditions.

Monitoring is ongoing

"[We] will continue to monitor post-marketing adverse events of visual disturbance and will work with sponsors to enhance the quality of information provided in these reports. FDA continues to work with sponsors to study and assess the effects of PDE-5 inhibitors on vision," the statement adds.

"Label updates are common for all products; they enable patients and doctors to make informed decisions," said Pfizer spokesman Daniel Watts, adding it might take weeks to completely shift to the new labels and inserts, although the sildenafil web site and phone line are updated.

Tadalafil's manufacturer, Lilly ICOS, was proactive.

"On May 20, we revised the post-marketing adverse events surveillance section of the Cialis label in the 'precautions' section. It is on http://www.Cialis.com/" Lilly ICOS media relations representative Kendra Strup told Urology Times.

"Additional studies are under way," Strup added, but declined further comment on clinical activities, citing competitive issues.

Vardenafil's U.S. co-marketers, Schering-Plough and GlaxoSmithKline, issued a statement supporting the FDA move to revise labels on PDE-5 inhibitors, noting that the companies "continue to confer with other regulatory authorities worldwide."

The companies received one spontaneous report of NAION occurring in a man taking vardenafil.

"It is not possible to determine whether this event is related to the use of Levitra, to the patient's underlying risk factors for developing NAION, to a combination of these factors, or to other factors," the statement read.

The day after FDA announced the relabeling, the Washington Post published a letter dated June 24, 2005, from Sen. Charles Grassley (R-IA), chairman of the Senate Finance Committee, to FDA acting director Lester Crawford, MD, asking why, after an FDA safety evaluator had recommended a label change for sildenafil on March 1, 2004, nothing had been done. FDA officials disclosed the reports of blindness in PDE-5 users in May 2005.