Dapoxetine (Priligy)

What dapoxetine is and how it works

Dapoxetine is a selective serotonin reuptake inhibitor, an SSRI. Other substances in this group are taken daily as antidepressants. Dapoxetine was developed specifically for on-demand use and has been approved in Germany as Priligy since April 23, 2009.

Ejaculation is controlled mainly via the sympathetic nervous system, triggered by a reflex center in the spinal cord, which in turn is influenced by nuclei in the brain. Dapoxetine inhibits the reuptake of serotonin into nerve cells and thus enhances its effect; according to the summary of product characteristics, the delay is presumably based on this. The decisive factor is the short duration of action: the initial half-life is about 1.5 hours, 24 hours after intake less than 5 percent of the peak level remains in the blood, and the terminal half-life is about 19 hours.

What the studies show

Five phase 3 trials analyzed together

McMahon 2011 pooled five randomized, double-blind trials with 6,081 men who met the diagnostic criteria for premature ejaculation. The time from penetration to ejaculation was measured with a stopwatch. From a baseline of 0.9 minutes, it rose after 12 weeks to 3.1 minutes under 30 mg and 3.6 minutes under 60 mg, and to 1.9 minutes under placebo; as a geometric mean, this corresponds to a 2.5-fold and 3-fold prolongation, respectively, compared with 1.6-fold under placebo. All questionnaire scores improved markedly. The most common side effects were nausea, dizziness and headache; anxiety, restlessness, suicidal thoughts or mood changes were not found in the questionnaires, and neither was a discontinuation syndrome.

The US approval trials

Pryor 2006 (Lancet) analyzed two identically designed 12-week trials at 121 centers in the US with 2,614 men. The time to ejaculation rose from about 0.9 minutes to 2.78 minutes under 30 mg and 3.32 minutes under 60 mg, and to 1.75 minutes under placebo. Nausea occurred in 8.7 and 20.1 percent, respectively.

Long-term trial in 22 countries

Buvat 2009 treated 1,162 men over 24 weeks. The mean time rose from 0.9 minutes to 3.2 and 3.5 minutes compared with 1.9 minutes under placebo. Because of side effects, 1.3 percent under placebo, 3.9 percent under 30 mg and 8.2 percent under 60 mg discontinued. Only 618 men completed the trial.

With concomitant erectile dysfunction

McMahon 2013 studied 495 men with premature ejaculation and erectile dysfunction who were already taking a PDE5 inhibitor such as sildenafil or tadalafil at a stable dose. The time to ejaculation at the end was 5.2 versus 3.4 minutes under placebo; 56.5 versus 35.4 percent rated their condition as at least “better”. The German summary of product characteristics nevertheless does not provide for this combination: Priligy should not be used in men with erectile dysfunction who are taking PDE5 inhibitors.

What users report

Two observational studies show how men use dapoxetine in everyday life. Of 120 men with lifelong premature ejaculation, 20 percent did not start treatment at all, mostly out of reluctance to take a “medication” or because of the cost; of the rest, 10.4 percent were still taking dapoxetine after one year. The reasons they gave were an effect below expectations, cost, side effects, declining interest in sex and lack of effect (Mondaini 2013). In a second study with 182 men, 87.3 percent had stopped after 12 months and 90.1 percent after 2 years, most often because of the cost (29.9 percent) and out of disappointment that the problem is not cured and the tablet is needed every time (25 percent); 11.6 percent cited side effects (Park 2017).

Where the data stop

• Size of the effect. The prolongation is statistically clear but limited in absolute terms: on average about one and a half minutes more than under placebo. Whether that is enough for the individual is shown by the high discontinuation rates in everyday life.
• Long-term use. According to the summary of product characteristics, only limited data are available beyond 24 weeks; continuation should be reassessed at least every six months.
• Certain groups. Efficacy and safety from age 65 are not established. There are no data for men without a confirmed diagnosis; it should only be prescribed after diagnosis.
• Trial participants. The large trials mostly included only men in stable relationships (Buvat 2009).

Status, approval and legal

Priligy 30 mg and 60 mg has been approved in Germany since April 23, 2009, and is prescription-only. The indication is premature ejaculation in men aged 18 to 64 who meet certain criteria, including a time to ejaculation of less than two minutes, poor control and marked distress. The approved dosage according to the summary of product characteristics: start with 30 mg on demand about 1 to 3 hours before sexual activity; if that is not sufficient and no relevant side effects or warning signs of fainting have occurred, a maximum of 60 mg. Dapoxetine must not be taken more often than once every 24 hours and is not intended for daily use. After the first four weeks or at the latest after 6 doses, the physician should reassess benefit and risk.

Because some EU member states questioned the additional benefit of the 60 mg tablet in relation to the fainting risk, a referral procedure followed. In 2011 the EMA’s medicines committee concluded that the benefit of the 60 mg tablet also outweighs the risks and that the fainting risk is manageable; the European Commission decided accordingly in 2012. The condition is that no one starts with 60 mg.

Safety

The most common side effects are nausea (11.0 percent under 30 mg, 22.2 percent under 60 mg), dizziness (5.8 and 10.9 percent), headache (5.6 and 8.8 percent) and diarrhea (3.5 and 6.9 percent). The most important risk is fainting: in the phase 3 trials it occurred in 0.06 percent under 30 mg to 0.23 percent under 60 mg, and in healthy volunteers in phase 1 trials in up to 0.64 percent. It was mostly vasovagal fainting, often in the first 3 hours after intake and frequently with warning signs such as nausea, dizziness, palpitations or sweating (summary of product characteristics). The analysis of the approval program found no QT prolongation and no other relevant cardiovascular events (Kowey 2011).

The summary of product characteristics calls for a medical examination with an orthostatic test before starting, that is, blood pressure and pulse lying down and standing up. Contraindications include heart failure, cardiac conduction disorders, ischemic heart disease, heart valve disease, a history of fainting, mania or severe depression and moderate to severe liver impairment. It must not be combined with MAO inhibitors, other SSRIs and SNRIs, tricyclic antidepressants, St. John’s wort, triptans, tramadol and strong CYP3A4 inhibitors. Alcohol should be avoided, because it can increase dizziness and the risk of fainting.

Sources

• Summary of product characteristics Priligy 30 mg/60 mg film-coated tablets, as of 07/2021 – indication, dosage, syncope, side effects (German)
• EMA – Priligy, referral under Article 29(4), opinion 2011, decision 2012
• McMahon CG et al., J Sex Med 2011 – pooled analysis of five phase 3 trials with 6,081 men
• Pryor JL et al., Lancet 2006 – two randomized trials with 2,614 men
• Buvat J et al., Eur Urol 2009 – phase 3 trial in 22 countries, 1,162 men, 24 weeks
• McMahon CG et al., J Sex Med 2013 – RCT with concomitant erectile dysfunction on a PDE5 inhibitor, 495 men
• Kowey PR et al., Drugs R D 2011 – cardiovascular safety in the approval program, syncope
• Park HJ et al., Sex Med 2017 – discontinuation of treatment in everyday life, 182 patients over 2 years
• Mondaini N et al., Urology 2013 – acceptance and discontinuation of treatment, 120 patients over 1 year
• German Ordinance on Prescription-Only Medicines (AMVV), Annex 1 – prescription requirement