Tadalafil Effective for Up to 36 Hours in More Than Half of Patients With ED

Laurie Barclay, MD

July 11, 2003

July 11, 2003 -- Tadalafil was effective for up to 36 hours in more than half of patients with erectile dysfunction (ED), which was about twice the effect of placebo, according to the results of a double-blind, randomized trial published in the July issue of Urology. The editorialists comment favorably on the role of tadalafil in the therapeutic armamentarium for ED.

"Tadalafil (Cialis, Lilly ICOS LLC...) is a potent, reversible, and selective PDE5 inhibitor for the treatment of ED. Compared with sildenafil (Viagra, Pfizer), tadalafil has an extended terminal half-life, 17.5 hours versus 3.7 hours, suggesting a lengthened period of responsiveness," write Hartmut Porst, a urologist in Hamburg, Germany, and colleagues. "This was not a study of efficacy per se or the time of maximum efficacy; rather, it was designed to determine whether tadalafil was associated with a treatment effect that could be discriminated from the effect of placebo for at least 24 and 36 hours."

In this European and U.S. multicenter, parallel-group study of 348 men with ED, patients were stratified by baseline severity of ED and then randomized to receive tadalafil 20 mg or placebo. Subjects were then randomized to two 4-week treatment intervals, during which they were requested to attempt sexual intercourse approximately 24 or 36 hours after tadalafil or placebo dosing.

Of the 348 patients, 327 (94%) completed the trial, including 163 of 175 in the tadalafil group and 164 of 173 in the placebo group. At 36 hours after dosing, 59.2% of intercourse attempts were successful (completed to ejaculation) in the tadalafil group compared with 28.3% in the placebo group ( P < .001). At 24 hours, 52.9% of intercourse attempts were successful in men receiving tadalafil compared with 29.1% in men receiving placebo ( P < .001).

"The advent of a pharmacologic agent such as tadalafil, with a period of responsiveness that begins soon after dosing and lasts up to 36 hours, may allow men and their partners more freedom in the timing of their sexual activity," the authors write. "Unlike currently available treatments, tadalafil may, for example, enable a patient to take a pill on a Friday evening and have intercourse with his partner on Saturday night or Sunday morning. The broad therapeutic coverage conferred by tadalafil, which can be taken without restrictions on alcohol or food intake, might translate to enhanced convenience and simplicity of administration, traits that are valued by men with ED."

Tadalafil was well tolerated, although treatment-emergent headache, flushing, dyspepsia, and myalgia were more common than in the placebo group ( P < .05 for all). There were no reported cardiovascular events, or any clinically significant effects of tadalafil on electrocardiographic findings, heart rate, or blood pressure.

Lilly ICOS LLC funded this study. Authors H. Porst, H. Padma-Nathan, F. Giuliano, and R. Rosen are paid consultants to both the sponsor of this study and competitors, are study investigators funded by the sponsor, and are members of the speaker's bureau for the sponsor. G. Anglin and L. Varanese are employees of and hold stock in the sponsor.

"Just how tadalafil will fit into our therapeutic armamentarium vis-à-vis other PDE5 inhibitors (and future remedies unknown) will not become clear until the widespread use expected after Food and Drug Administration approval," Leonard S. Marks, MD, from Urological Sciences Research Foundation in Culver City, California, writes in an accompanying editorial. "[Its] convenience must be weighed against the possibility of a lingering undesirable effect in some men."

Dr. Marks notes that in Europe, where the drug was approved in November 2002, the package leaflet warns that men using organic nitrates and nitric oxide donors, and men with serious heart disease, recent stroke or myocardial infarction, and uncontrolled blood pressure should not take tadalafil.

"It is noteworthy that the side-effect and discontinuation profiles were modest and no greater than those reported elsewhere with other PDE5 inhibitors with substantially shorter half-lives of elimination," Arthur L. Burnett II, MD, from Johns Hopkins Hospital in Baltimore, Maryland, writes in an accompanying editorial. "Why the medication affords a prolonged efficacy without yielding greater severity or prolongation of adverse effects is puzzling and remains unexplained.... Continued scientific investigation in the field is absolutely necessary to understand the pathophysiologic conditions associated with ED and to develop specific therapies that are truly corrective."

Urology. 2003;62:121-125, 125-126

Reviewed by Gary D. Vogin, MD

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