Dapoxetine HCL Information
Dapoxetine (Priligy, Westoxetin) is a very short-acting selective serotonin reuptake inhibitor (SSRI) marketed and indicated as a treatment for premature ejaculation. Compared to longer-acting SSRIs such as those typically available for antidepressant use, dapoxetine has been deemed suitable for “on-demand” use taken 1-3 hours before sexual activity. Though approved in over 50 other countries, dapoxetine is currently in phase III (human) trials in the US FDA approval process.
Prior to approval and availability of dapoxetine as a drug-based treatment for premature ejaculation, psychotherapy and guided counseling were the only treatment options commonly available to men complaining of premature ejaculation. Though it is the most common male sexual disorder, affecting 20-30% of men globally, lack of formal scientific studies focused on PE until recently mean it is not as well-understood as other forms of sexual dysfunction. According to Rowland (2011), “unlike erectile dysfunction, which increases with age, rates of PE remain constant across the adult life span”. Other drugs have also been tried or investigated as PE treatments, generally with less success than dapoxetine, including tramadol, topical anesthetics, and PDE5 inhibitors.
Antidepressants are known to delay ejaculation in patients with or without premature ejaculation, who are usually using them for other reasons; however, most patients diagnosed with premature ejaculation (PE) are unlikely to have depression. Long-acting SSRIs have an unfavorable safety profile for treatment of PE in healthy men. Unlike antidepressants, dapoxetine does not require daily use for efficacy, and boasts a better safety profile for premature ejaculation:
Premature ejaculation (PE) is the most common male sexual dysfunction. Dapoxetine hydrochloride, belonging to a class of drugs known as selective serotonin reuptake inhibitors or, was the first drug originally approved for the on-demand treatment of men with PE. We aimed to compare the intravaginal ejaculatory latency time (IELT), patient-reported global impression of change (PGIC), and adverse effect (AE) incidence associated with the use of dapoxetine (30 mg and 60 mg) versus placebo, and evaluate the differences in administering 60 mg versus 30 mg as on-demand medical oral therapy for the treatment of PE via a literature review and meta-analysis. Relevant randomized controlled trials (RCTs) were identified from PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (Cochrane Library) databases. Ultimately, a total of seven RCTs with 8039 patients were included. Our meta-analysis demonstrated that dapoxetine (in the 30 mg and 60 mg subgroup) resulted in significantly higher IELT, PGIC, and AE incidence relative to the placebo, with higher proportions observed for 60 mg versus 30 mg of dapoxetine administration. The most common AEs were mild and tolerable. We conclude that dapoxetine (particularly the 60 mg dosage) may be considered a safe and effective drug for patients with PE.
In a randomized, double-blinded trial, secondary effects of premature ejaculation such as personal distress, interpersonal difficulty in relationships, and low satisfaction with sexual intercourse were improved, and dapoxetine was well-tolerated.
Modi et al discuss pharmacokinetics of dapoxetine:
Dapoxetine was rapidly absorbed following oral administration, with peak plasma concentrations reached approximately 1 hour after dosing; plasma concentrations after single doses of dapoxetine decreased rapidly to approximately 5% of peak concentrations by 24 hours. Elimination was biphasic, with an initial half-life of approximately 1.4 hours and a terminal half-life of approximately 20 hours. Dapoxetine showed time-invariant pharmacokinetics and dose proportionality between doses, and its pharmacokinetics was unaffected by multiple dosing. The pharmacokinetics of dapoxetine metabolites, desmethyldapoxetine and dapoxetine-N-oxide, was similarly unaffected by multiple dosing.
As the first compound indicated and developed for premature ejaculation, dapoxetine was at the center of a controversy; see, for example, a comment by Waldinger and Schweitzer (2008):
Time until ejaculation during sexual intercourse is highly variable. Some men and their partners find sex unsatisfactory because they feel ejaculation occurs too quickly. Psychobehavioural therapy is the first option. Dapoxetine, a short-acting serotonin reuptake inhibitor, is the first drug to be authorised for use in premature ejaculation in some EU member states. Four double-blind randomised placebo-controlled trials in a total of 4414 men are available. At best, only one in three men and one in five women perceived at least a moderate improvement in sexual satisfaction through a specific effect of dapoxetine. A substantial placebo effect was observed in one-third of participants of both sexes. Dapoxetine exposes men to the numerous adverse effects of all serotonin reuptake inhibitors, some of which can be severe, such as self-harm, aggressive behaviour, and serotonin syndrome. Postural hypotension and syncope can also occur. Dapoxetine is strongly metabolised by the cytochrome P450 isoenzymes CYP 3A4 and CYP 2D6, and thus carries a risk of numerous pharmacokinetic interactions. In practice, there is no justification for exposing men to potentially serious adverse effects for only a moderate symptomatic improvement in a poorly defined disorder. Behavioural approaches should remain the cornerstone of therapy.
The same researchers in a different paper question the state of the peer-review process as it pertains to studies funded by pharmaceutical companies pertaining to antidepressants, citing the concern that “PE drug treatment research is a young and dynamic field, and its development deserves transparency to its development[sic].”
News – Johnson & Johnson Prescrire Int. 2010 Feb;19(105):12-4.
Kendirci M, Salem E, Hellstrom WJ . Dapoxetine, a novel selective serotonin transport inhibitor for the treatment of premature ejaculation. Ther Clin Risk Manag 3 (2): 277–89. 2007.
Janssen-Cilag EMEA announces receipt of first regulatory approvals for Priligy for PE in Finland and Sweden. (2/11/2009)
De Hong C, Ren LL, Yu H, Qiang W. The role of dapoxetine hydrochloride on-demand for the treatment of men with premature ejaculation. Scientific Reports 4, Article number: 7269 (2014).
Gur S, Kadowitz PJ, Sikka SC.Current therapies for premature ejaculation. Drug Discov Today. 2016 Jul;21(7):1147-54.
Rowland DL. Psychological impact of premature ejaculation and barriers to its recognition and treatment. Curr Med Res Opin. 2011 Aug;27(8):1509-18.
Safarinejad MR .Safety and Efficacy of Dapoxetine in the Treatment of Premature Ejaculation: A Double-Blind, Placebo-Controlled, Fixed-Dose, Randomized Study.Neuropsychopharmacology 33: 1259. (2007).
Modi NB, Dresser MJ, Simon M, Lin D, Desai D, Gupta S. Single- and multiple-dose pharmacokinetics of dapoxetine hydrochloride, a novel agent for the treatment of premature ejaculation. J Clin Pharmacol. 2006 Mar;46(3):301-9.
Waldinger MD, Schweitzer DH. Dapoxetine. Premature ejaculation: not worth the risk. J Sex Med. 2008 Apr;5(4):966-97.
Waldinger MD, Schweitzer DH. Premature ejaculation and pharmaceutical company-based medicine: the dapoxetine case. J Sex Med. 2008 Apr;5(4):966-97.