Dapoxetine, which is structurally related to fluoxetine (Fluctine® and others), binds to proteins involved in neurotransmitter transport and blocks the reuptake of primary serotonin. It can therefore also be assigned to the selective serotonin reuptake inhibitors (SSRI). The effect of dapoxetine on premature ejaculation is not clear. Serotonin reuptake inhibition is thought to affect the spinal reflex arc that mediates ejaculation. Since the lateral paragigantocellular nucleus is a structure in the brainstem that helps control the ejaculation reflex, supraspinal mechanisms of action are also postulated for dapoxetine.
Dapoxetine is rapidly absorbed after oral administration. The peak plasma level can be measured after 1 to 1.5 hours. The biological availability is around 40% on average but shows a wide range.
Dapoxetine is converted to various metabolites primarily catalyzed by CYP3A4, CYP2D6, and flavin-dependent monooxygenase type 1 (FMO1). The main metabolite, dapoxetine N-oxide, has little pharmacological activity; another metabolite, desmethyl-dapoxetine, has approximately the same pharmacological activity as the parent drug but is present in plasma at low levels. The final excretion of the – conjugated – metabolites takes place via the kidneys. The elimination of dapoxetine is biphasic, with an initial half-life of approximately 1.5 hours and a terminal half-life of the order of 20 hours. In the case of impaired liver function, the area under the concentration-time curve can increase up to threefold.
In the phase III studies, dapoxetine was compared with placebo in double-blind adult men with premature ejaculation. Premature ejaculation was defined as occurring within 2 minutes of vaginal penetration in at least 75% of cases; Based on DSM-IV criteria (“Diagnostic and Statistical Manual of Mental Disorders”), a corresponding level of psychological distress had to arise for participation in the study to be considered. The men who took part in the studies were instructed to plan on having intercourse with their partners several times a month and to take dapoxetine 1 to 3 hours beforehand (max one dose per 24 hours). As the primary endpoint the time that elapsed after penetration until ejaculation occurred was determined, the so-called «intravaginal ejaculatory latency time» (IELT).
Two studies conducted using the same protocol were combined into one publication, bringing together a total of 2614 men. From this, three groups were formed, in which dapoxetine (30 mg or 60 mg) or placebo was used. A significant difference in IELT in favor of dapoxetine was already detectable after the first dose. At 12 weeks, IELT had increased on average from 54 seconds to 1 minute 45 seconds with placebo, from 55 seconds to 2 minutes 47 seconds with the lower dose of dapoxetine, and from 55 seconds to 3 minutes 19 seconds with the higher dose. As a secondary endpoint among other things, it was determined how satisfactorily the sexual act was experienced. A scale ranging from 0 (“not at all satisfied”) to 4 (“very satisfied”) was used. With placebo, the average score increased from 1.66 to 1.70 in men and from 1.59 to 1.69 in women, with the lower dose of dapoxetine from 1.65 to 2.21 (men) and from 1.65, respectively 1.62 to 2.11 (partners) and with the higher dapoxetine dose from 1.72 to 2.31 (men) and from 1.74 to 2.32 (partners).
Another study with 1162 participants lasted 24 weeks. It provided a similar picture, with both doses of dapoxetine delaying ejaculation significantly longer than placebo. The percentage of men who classified the premature ejaculation as improved or significantly improved in the overall assessment was also higher with dapoxetine: it was 16% with placebo, 31% with the lower dapoxetine dose, and 39% with the higher dose.
A comparison with paroxetine (Deroxat® and others) suggests that dapoxetine is basically no more effective than other SSRIs. 309 men received double-blind dapoxetine (twice 30 mg/day), paroxetine (twice 10 mg/day) or placebo, albeit as a 12-week long-term treatment. IELT increased from an average of 38 seconds to 2 minutes 59 seconds with dapoxetine, from 31 seconds to 6 minutes 10 seconds with paroxetine, and from 34 to 55 seconds with placebo.
Side effects reported after taking dapoxetine included nausea, dizziness, headache, diarrhea, fatigue, insomnia, dry mouth, increased sweating, blurred vision, nervousness, and nasopharyngitis. Dapoxetine produced orthostatic hypotension slightly more frequently than placebo. In rare cases, syncope has occurred with dapoxetine, the cause of which was most likely thought to be vasovagal. About 1% of men using dapoxetine reported sexual dysfunction (decreased libido, erectile dysfunction, etc.).
For people who take dapoxetine regularly, not taking it can lead to mild withdrawal symptoms.
Concomitant administration of strong CYP3A4 or CYP2D6 inhibitors can increase dapoxetine exposure almost two-fold. The effect of CYP3A4 inhibitors on dapoxetine clearance is particularly pronounced in individuals with reduced CYP2D6 activity (“poor metabolizer”). Dapoxetine itself has some CYP2D6 inhibitory activity.
If dapoxetine is combined with other antidepressants (SSRIs, tricyclics, St. John’s wort) or serotoninergic substances, there is a risk of serotonin syndrome. Dapoxetine users should also not consume substances that are circulating as “party drugs” such as ketamine, methylenedioxymethamphetamine (MDMA, ecstasy), or LSD because of an increased risk of arrhythmias, hyperthermia, and serotonin syndrome.
Dapoxetine (Priligy®) is available as a 30 mg film-coated tablet and is approved for the treatment of premature ejaculation in men aged 18 to 65. It is recommended to take the tablets 1 to 3 hours before planned sexual activity, maximum once every 24 hours. If the 30 mg dose is well tolerated but insufficiently effective, it can be doubled to 60 mg. Dapoxetine should only be used when needed and not in the form of long-term therapy. Before prescribing dapoxetine, blood pressure and pulse must be measured while lying and standing to rule out a tendency to orthostasis. Dapoxetine should not be used in moderate or severe hepatic insufficiency; among the contraindications are also listed severe renal dysfunction and heart disease.
The ejaculation-inhibiting effect of serotonin reuptake inhibitors (SSRI) is one of their well-known (side) effects, and if a new area of application is derived from this, it is not a big surprise. The reason dapoxetine was chosen for this is not that it was particularly effective at delaying ejaculation compared to other SSRIs; rather, it is dapoxetine’s pharmacokinetic properties that make it slightly more suitable for on-demand use. But the mere idea of using a pill to hope for a 1 to 2 minute longer sexual act a few hours later, and thereby exposing yourself to the risk of syncope and other side effects, contains enough absurdity that in itself is considered able to comment.
The problem of premature ejaculation can also be tackled with local anesthetics – for example in the form of creams or coated condoms. This method has not been compared to dapoxetine, but it should help at least as well and cause hardly any side effects. All the more one will call Dapoxetine a superfluous drug.
How long does it take for dapoxetine to work?
The SSRI dapoxetine takes effect around 1 hour after ingestion
How long does dapoxetine work?
The dapoxetine duration of action is just under 3 hours, the half-life is reached after 90 minutes. Accordingly, the drug should be taken 1 to 3 hours before sexual intercourse.
Is Dapoxetine Dangerous?
If the drug is taken properly with medical indication, the use of dapoxetine is usually harmless. However, a detailed medical history by a doctor is a prerequisite for the safe use of Dapoxetine
Can I take dapoxetine and alcohol together?
If the intake of dapoxetine is planned, alcohol should be avoided. The combination of Priligy and alcohol increases the chance of side effects such as fainting, dizziness, or sleepiness.
How long can dapoxetine be kept?
The shelf life of dapoxetine is 3 years. So you can use up your pack in a relaxed manner.
What is the maximum dose of dapoxetine?
The prescribed dose of the active ingredient dapoxetine in Priligy should not be exceeded under any circumstances.
In addition, the medication may only be taken a maximum of once per 24 hours.
Can Dapoxetine and Sildenafil (Viagra) be taken together?
The drugs Priligy and Sildenafil (Viagra) must not be combined. The reason for this is possible dangerous interactions between the two active ingredients dapoxetine and sildenafil.
Can Dapoxetine and Tadalafil (Cialis) be taken together?
The drugs Cialis and Priligy must not be combined. As with Priligy and Viagra, this is due to dangerous interactions between the active ingredients, i.e. dapoxetine and tadalafil.