Premature ejaculation therapy does not interact with PDE-5 inhibitors

Mountain View, CA-Apparently avoiding problems with a potentially common drug combination, the investigational premature ejaculation therapy dapoxetine does not interact with phosphodiesterase type-5 inhibitors, according to results of a clinical pharmacokinetics study.

The combination of dapoxetine and sildenafil citrate (Viagra) or tadalafil (Cialis) resulted in minimal differences in pharmacokinetic parameters compared with dapoxetine alone in healthy volunteers. Sildenafil did increase overall exposure to dapoxetine, but the effect is not considered clinically significant, as reported at the AUA annual meeting.

"There were no statistically significant differences in peak concentration, time of peak, or half-life of dapoxetine given alone or in combination with a PDE-5 inhibitor," said lead author Mark Dresser, PhD, a clinical pharmacologist with ALZA Corp., Mountain View, CA.

Dapoxetine is a serotonin transporter inhibitor that has demonstrated safety and efficacy in the treatment of PE (J Urol 2004; 172:290-4). The drug has been shown to be effective when used on demand and on the first dose, according to another study reported at the AUA meeting (J Urol 2005; 173[suppl]:201, abs. 740).

Some men have concurrent PE and erectile dysfunction, raising the possibility of concomitant use of dapoxetine and PDE-5 inhibitors, Dr. Dresser said. To determine whether dapoxetine interacts with PDE-5 inhibitors, 22 healthy men ages 18 to 45 years were enrolled in a randomized, single-dose, crossover study that had three treatment arms. Each man received dapoxetine, 60 mg; dapoxetine plus tadalafil, 20 mg; and dapoxetine plus sildenafil, 100 mg. Each treatment arm was separated by a 6- to 14-day washout period.

Plasma samples were collected before dosing and for 72 hours after dosing. The samples were analyzed by liquid chromatography tandem mass spectrometry for dapoxetine and its metabolites, as well as tadalafil and sildenafil.

No adverse effects

Co-administration of tadalafil or sildenafil with dapoxetine had no effect on plasma concentrations of dapoxetine, Dr. Dresser reported. Dapoxetine plasma levels rapidly reached peak plasma concentration and decreased to 5% of peak plasma concentration by 24 hours, whether administered alone or in combination with a PDE-5 inhibitor. Dapoxetine metabolites also were unaffected by concomitant administration of the PDE-5 inhibitors.

Sildenafil did increase dapoxetine exposure, as reflected by area under the curve.

"With sildenafil, there was approximately a 22% increase in overall exposure to dapoxetine, which was statistically significant," said Dr. Dresser. "Given the small magnitude of the change, we felt that this difference was unlikely to be clinically meaningful."

No serious adverse effects occurred during the study, and no patient withdrew from the study because of adverse events.

"Tadalafil and sildenafil have minimal impact on dapoxetine pharmacokinetics," Dr. Dresser concluded. "Maximum doses of tadalafil and sildenafil were used, as were the maximum dose of dapoxetine studied in phase III trials. The combination of dapoxetine with PDE-5 inhibitors was well tolerated."