Agent for premature ejaculation shows no interactions with PDE-5 inhibitors

May 24, 2005

Dapoxetine, the first treatment developed specifically for premature ejaculation, has no significant interaction when taken concurrently with the type-5 phosphodiesterase type-5 inhibitors sildenafil citrate (Viagra) and tadalafil (Cialis), according to results presented here yesterday.

Dapoxetine, the first treatment developed specifically for premature ejaculation, has no significant interaction when taken concurrently with the phosphodiesterase type-5 inhibitors sildenafil citrate (Viagra) and tadalafil (Cialis), according to results presented here yesterday.

"Tadalafil and sildenafil have minimal impact on the pharmacokinetics of dapoxetine," said Mark Dresser, PhD, of Alza Corp. in Mountainview, CA. "Maximal doses of the two PDE-5 inhibitors were evaluated, as well as the highest dapoxetine dose evaluated in phase III trials. It appeared these combination treatments were well tolerated."

The study has relevance for men who have premature ejaculation and concurrent erectile dysfunction, said Dr. Dresser. A drug for premature ejaculation would likely be used in combination with PDE-5 inhibitors by at least some patients.

To evaluate the potential for drug interactions and the tolerability of the combinations, investigators randomized 22 healthy men aged 18 to 45 years to one of three treatments: dapoxetine, 60 mg, or dapoxetine, 60 mg in combination with tadalafil, 20 mg, or sildenafil, 100 mg. Plasma samples were collected 0 to 72 hours after administration and evaluated by liquid chromatography and mass spectrometry. The men were crossed over until they received all three treatments, which were separated by a washout period of 6 to 14 days.

Dapoxetine rapidly reached maximum concentration and decreased to 5% of maximum concentration over 24 hours. Neither tadalafil nor sildenafil affected maximum plasma concentrations of dapoxetine compared with dapoxetine alone. Tadalafil also had no impact on dapoxetine area under the curve. Exposure to dapoxetine, as reflected by AUC, increased by 20% in combination with sildenafil, but Dr. Dresser said the difference is not likely to be clinically meaningful. Additionally, tadalafil and sildenafil pharmacokinetics were unaffected by dapoxetine.

Co-administration of dapoxetine, a serotonin transporter inhibitor, with the PDE-5 inhibitors did not affect the incidence of adverse events, which were reported by 43.5% of men during dapoxetine monotherapy and by 47.8% during combination treatment. Clinical assessments, including vital signs and ECG, were not affected by dapoxetine alone or in combination with the PDE-5 inhibitors.