Dapoxetine. marketed as Priligy and Westoxetin. among and other brands, is the first compound developed specially for the treatment of premature ejaculation (PE) in men 18вЂ“64 years old.   Dapoxetine works by inhibiting the serotonin transporter. increasing serotonin’s action at the post synaptic cleft, and as a consequence promoting ejaculatory delay.  As a member of selective serotonin reuptake inhibitor (SSRI) family, dapoxetine was initially created as an antidepressant. However, unlike other SSRIs, dapoxetine is absorbed and eliminated rapidly in the body. Its fast acting property makes it suitable for the treatment of PE but not as an antidepressant. 
Originally created by Eli Lilly pharmaceutical company, dapoxetine was sold to Johnson & Johnson in 2003 and submitted as a New Drug Application to the Food and Drug Administration (FDA) for the treatment of PE in 2004.  Dapoxetine has been sold in several European and Asian countries, and lately in Mexico. In the US, dapoxetine has been stuck in phase III development since 2003. However, it is expected to be marketed soon.  In 2012, Menarini acquired the rights to commercialise Priligy in Europe, most of Asia, Africa, Latin America and the Middle East. 
Premature ejaculation Edit
Randomized, double blind, placebo-controlled trials have confirmed the efficacy of dapoxetine for the treatment of PE.  Different dosage has different impacts on different type of PE. Dapoxetine 60 mg significantly improves the mean intravaginal ejaculation latency time (IELT) compared to that of dapoxetine 30 mg in men with lifelong PE, but there is no difference in men with acquired PE.  Dapoxetine, given 1вЂ“3 hours before sexual episode, prolongs IELT, increases the sense of control and sexual satisfaction in men of 18 to 64 years of age with PE. Since PE is associated with personal distress, interrelationship difficulty, dapoxetine provides help for men with PE to overcome this condition.  Because lack of specific approval treatment for PE in the US and some other countries, other SSRIs such as fluoxetine. paroxetine. sertraline. fluvoxamine. and citalopram have been used as off label drugs to treat PE. Waldinger’s meta analysis shows that the use of these conventional antidepressants increasing IELT from two to ninefold above base line in comparison of three to eightfold when dapoxetine is used.  However, these SSRIs must be taken daily in order to achieve meaningful efficacy, and the long half-life increases the risk of the drug accumulation and as a consequence increased of adverse effects such as decreasing sexual libido and causing erectile dysfunction.  Dapoxetine, on the other hand, is a fast-acting SSRI. It is rapidly absorbed and eliminated from the body within a few hours. This favorable pharmacokinetics minimizes the risk of the drug’s accumulation in the body, and therefore reducing side effects. 
A contraindication is a situation in which a drug should not be used, because it may be harmful to the patient.  Dapoxetine should not be used in men with moderate to severe hepatic impairment and in those receiving CYP3A4 inhibitors such as ketoconazole, ritonavir, and telithromycine. Dapoxetine can also not be used in patients with heart failure, permanent pacemaker, or other significant ischemic heart disease. Caution is advised in men receiving thioridazine. monoamine oxidase inhibitors. SSRIs, serotonin-norepinephrine reuptake inhibitors. or tricyclic antidepressant. If a patient stops taking one of these drugs, he should wait for 14 days before taking dapoxetine. If a patient stops taking dapoxetine, he should wait for 7 days before receiving these drugs. 
The most common effects when taking dapoxetine are nausea, dizziness, dry mouth, headache, diarrhea, and insomnia.   Discontinuation due to adverse effects is dose related. According to McMahon in recent study in Asia, the rate of discontinuation is 0.3%, 1.7%, and 5.3% of 1067 studied subjects with placebo, dapoxetine 30 mg, and dapoxetine 60 mg respectively.  Unlike other SSRIs used to treat depression, which have been associated with high incidences of sexual dysfunction.  dapoxetine is associated with low rates of sexual dysfunction. Taken as needed, dapoxetine has very mild adverse effects on loss of libido (<1%) and ED (<4%). 
No case of the drug overdose has been reported during clinical trials. 
Many men that have PE also suffer from erectile dysfunction (ED). Treatment for these patients should consider the drug-drug interaction between dapoxetine and PDE5 inhibitors such as tadalafil (Cialis) or sildenafil (Viagra). In Dresser study (2006), plasma concentration of 24 subjects was obtained. Half of the sample pool were treated with dapoxetine 60 mg + tadalafil 20 mg; the other half were treated with dapoxetine 60 mg + sildenafil 100 mg. These plasma samples were then analyzed using liquid chromatography-tandem mass spectrometry. The results showed that dapoxetine does not alter the pharmacokinetic of tadalafil or sildenafil. 
Ethanol doesn’t affect the pharmacokinetics of dapoxetine when taking concurrently with dapoxetine. 
Mechanism of actions Edit
The mechanism through which dapoxetine affects premature ejaculation is still unclear. However, it is presumed that dapoxetine works by inhibiting serotonin transporter and subsequently increasing serotonin’s action at pre and postsynaptic receptors  Human ejaculation is regulated by various areas in the central nervous system (CNS).  The ejaculatory pathway originates from spinal reflex at the thoracolumbar and lumbosacral level of spinal cord activated by stimuli from male genital. These signals are relayed to the brain stem. which then is influenced by a number of nuclei in the brain such as medial preoptic and paraventricular nulcei.  Clement’s study performed on anaesthetized male rats showed that acute administration of dapoxetine inhibits ejaculatory expulsion reflex at supraspinal level by modulating activity of lateral paragigantocellular nucleus (LPGi) neurons. These effects cause an increase in pudendal motoneuron reflex discharge (PMRD) latency. However, it is unclear whether dapoxetine acts directly on LPGi or on the descending pathway in which LPGi located. 
Dapoxetine is a white powder substance and water- insoluble. Taken 1вЂ“3 hours before sexual activity, it is rapidly absorbed in the body. Its maximum plasma concentration (Cmax ) is reached 1вЂ“2 hours after oral administration. The Cmax and AUC (Area Under the plasma vs. time Curve) are dose dependent. The Cmax and Tm (time needed to obtain the maximum plasma concentration) after single doses of dapoxetine 30 mg and 60 mg are 297 and 498 ng/mL at 1.01 and 1.27 hours respectively. A high fat meal does reduce the Cmax slightly, but it is insignificant. In fact, food doesn’t alter dapoxetine pharmacokinetics. Dapoxetine can be taken with or without food. 
Dapoxetine is absorbed and distributed rapidly in the body. Greater than 99% of dapoxetine is bound to the plasma protein. The mean steady state volume is 162 L. Its initial half-life is 1.31 hours (30 mg dose) and 1.42 hours (60 mg dose,) and its terminal half life is 18.7 hours (30 mg dose) and 21.9 hours (60 mg dose). 
Dapoxetine is metabolized extensively in the liver and kidney by multiple enzymes such as CYP2D6, CYP3A4, and flavin monooxygenase 1 (FMO1). The major product at the end of the metabolic pathway is circulating dapoxetine N-oxide, which is a weak SSRI and contributes no clinical effect. The other products presented less than 3% in the plasma are desmethyldapoxetine and didesmethydapoxetine. Desmethyldapoxetine is approximately equipotent to dapoxetine. 
The metabolites of dapoxetine are eliminated rapidly in the urine with a terminal half-life of 18.7 and 21.9 hours for a single dose of 30 mg and 60 mg respectively. 
Safety and tolerability Edit
The cardiovascular safety profile of dapoxetine has been studied extensively during the drug development. Phase I trials showed that dapoxetine had neither clinical significant electrocardiographic effects nor delayed repolarization effects, with dosing up to 4-fold greater than the maximum recommended dosage which is 60 mg. Phase III studies in men with PE showed a safety and well tolerate profile of dapoxetine with dosing of 30 and 60 mg. There is no cardiovascular adverse had been found. 
Studies of SSRIs in patients with major psychiatric disorders prove that SSRIs are potentially associated with certain neurocognitive adverse effects such as anxiety. akathisia. hypomania. changes in mood, or suicidal thought.   However, there is no study on the effects of SSRIs in men with PE. McMahonвЂ™s study in 2012 showed that dapoxetine has no effect on mood and is not associated with anxiety or suicidality. 
The incidence of antidepressant discontinuation syndrome symptoms in men using dapoxetine to treat premature ejaculation has been described by reviewers as low and/or no different from the incidence of such symptoms in men withdrawn from placebo treatment.    The lack of chronic serotonergic stimulation with onвЂ“demand dapoxetine minimizes the potentiation action of serotonin at synaptic cleft, thus decreasing the risk of DESS. 
Synthesis of dapoxetine
Currently very few methods are used to synthesize (S )-dapoxetine. This novel approach consists of only six steps in which three main steps are shown above. The initial reactant is trans -cinnamyl alcohol which is commercial available. Sharpless asymmetric epoxidation and Mitsunobu reaction have been used to produce expected (S )-dapoxetine. The overall yield is 35%. This method is considered a good choice compare to the known methods due to high yield and easily obtainable reactants. 
Dapoxetine was created by Eli Lilly and in phase I clinical trial as an antidepressant. However, It never worked out well as a medication for the treatment of depression and was shelved for a while before subsequently developed to treat PE. In December 2003, Eli Lilly sold patent of dapoxeine to Pharmaceutical Product Development (PPD) for 65 million US dollars in cash. Eli Lilly may also receive royalties payment from PPD if the sale exceeds certain amount.
ALZA is the current owner of dapoxetine. However, PPD will receive milestone payment and drug royalties from ALZA. If approved, dapoxetine will be marketed in the US by Ortho McNeil pharmaceutical, Inc. Ortho McNeil as well as Janssen-Ortho Inc, or Janssen-Cilag are all units of Johnson & Johnson. Dapoxetine is currently in phase III clinical trials, pending review by the Federal Drug Administration (FDA). 
Dapoxetine has been marketed and approved in more than 50 countries.  Dapoxetine has been approved in Italy, Spain, Mexico, South Korea, and New Zealand in 2009 and 2010; marketed in Sweden, Austria, Germany, Finland, Spain, Portugal, and Italy. It has also been approved in France, Russia, Malaysia, Philippines, Argentina, and Uruguay. 
Dapoxetine is sold under a variety of brand names including Dumax, Duratia, Kutub, Lejam, Pentenal-30, Priligy, Sustinex, and Westoxetin.
- ^ “Russian State Register of Medicines. Priligy (dapoxetine) Film-coated Tablets, for Oral Use. Full Prescribing Information” (in Russian). 25 July 2013. Retrieved 11 August 2016.
- ^ ab Dresser, M. J.; Desai, D.; Gidwani, S.; Seftel, A. D. & Modi, N. B. (2006). “Dapoxetine, a novel treatment for premature ejaculation, does not have pharmacokinetic interactions with phosphodiesterase-5 inhibitors”. International Journal of Impotence Research. 18 (1): 104вЂ“110. doi :10.1038/Sj.Ijir.3901420.
- ^ McMahon, CG (Oct 2012). “Dapoxetine: a new option in the medical management of premature ejaculation.”. Therapeutic advances in urology. 4 (5): 233вЂ“51. doi :10.1177/1756287212453866. PMC 3441133 . PMID 23024705.
- ^ abcd Government, A. ( 2010). Australian Public Assessment Report for Dapoxetine (D. o. H. a. A. T. G. Administration, Trans.).
- ^ abc Andersson, K. E.; Mulhall, J. P. & Wyllie, M. G. (2006). “Pharmacokinetic and pharmacodynamic features of dapoxetine, a novel drug for ‘on-demand’ treatment of premature ejaculation.”. Bju International. 97 (2): 311вЂ“315. doi :10.1111/J.1464-410x.2006.05911.X.
- ^ McCarty, E. & Dinsmore, W. (2012). “Dapoxetine: an evidence-based review of its effectiveness in treatment of premature ejaculation”. Core Evid. 7. 1вЂ“14. doi :10.2147/CE.S13841.
- ^ http://www.menarini.com/news/News-Archive/20122/Morrisville-N.C.-and-Florence-Italy-May-14-2012-NEWS-RELEASE
- ^ McMahon, C. G. McMahon, C. N. & Leow, L. J. (2006). New agents in the treatment of premature ejaculation. Neuropsychiatr Dis Treat, 2(4), 489-503.
- ^ ab Pryor, J. L.; Althof, S. E.; Steidle, C.; Rosen, R. C.; Hellstrom, W. J. G.; Shabsigh, R.; Kell, S. (2006). “Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials”. Lancet. 368 (9539): 929вЂ“937. doi :10.1016/s0140-6736(06)69373-2.
- ^ Shabsigh, R. Broderick, G. A. Miloslavsky, M. & Bull, S. (2006). Dapoxetine has long-term efficacy in the treatment of premature ejaculation. Journal of Urology, 175(4), 297-298.
- ^ Montague, D. K.; Jarow, J.; Broderick, G. A.; Dmochowski, R. R.; Heaton, J. P.; Lue, T. F.; Sharlip, I. D. (2004). “AUA guideline on the pharmacologic management of premature ejaculation. [Guideline Practice Guideline]”. J Urol. 172 (1): 290вЂ“294. doi :10.1097/01.ju.0000132159.61156.ea.
- ^ Contraindications. (2012) Retrieved 11/27, 2012, from http://www.drugs.com/enc/contraindications.html
- ^ Buvat, J. Tesfaye, F. Rothman, M. Rivas, D. A. & Giuliano, F. (2009). Dapoxetine for the Treatment of Premature Ejaculation: Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial in 22 Countries. European Urology, 55(4), 957-968. doi: Doi 10.1016/J.Eururo.2009.01.025
- ^ (French) (2013) В« Г‰jaculation prГ©coce. pas de dapoxГ©tine В» http://www.prescrire.org/fr/3/31/48533/0/NewsDetails.aspx
- ^ McMahon, C. G. Kim, S. W. Park, N. C. Chang, C. P. Rivas, D. Tesfaye, F. Aquilina, J. W. (2010). Treatment of Premature Ejaculation in the Asia-Pacific Region: Results from a Phase III Double-blind, Parallel-group Study of Dapoxetinejsm_1560256..268. J Sex Med, 7, 12.
- ^ Montejo, A. L.; Llorca, G.; Izquierdo, J. A.; Rico-Villademoros, F.; Psychotr, S. W. G. S. (2001). “Incidence of sexual dysfunction associated with antidepressant agents: A prospective multicenter study of 1022 outpatients”. Journal of Clinical Psychiatry. 62. 10вЂ“21.
- ^ Jhanjee, A. Kumar, P. Bhatia, M. S. & Srivastava, S. (2011). Dapoxetine-A Novel Drug for Premature Ejaculation. Delhi Psychiatry Journal, 14(1), 5.
- ^ ab Modi, N. B. Dresser, M. Desai, D. & Jazrawi, R. P. (2005). Dapoxetine for the treatment of premature ejaculation: Lack of interaction with ethanol. Journal of Urology, 173(4), 239-239.
- ^ Gengo, P. J. View, M. Giuliano, F. McKenna, K. E. Chester, A. Lovenberg, T. Gupta, S. K. (2005). Monoaminergic transporter binding and inhibition profile of dapoxetine, a medication for the treatment of premature ejaculation. Journal of Urology, 173(4), 239-239.
- ^ Goldstein, I. (2003, 11/17/12). The Central Mechanisms of Sexual Function Retrieved 11/11/12, 2012, from http://www.bumc.bu.edu/sexualmedicine/publications/the-central-mechanisms-of-sexual-function/
- ^ Giuliano, F. & Clement, P. (2005). Physiology of ejaculation: emphasis on serotonergic control. [Review]. Eur Urol, 48(3), 408-417. doi :10.1016/j.eururo.2005.05.017
- ^ Clement, P. Bernabe, J. Gengo, P. Denys, P. Laurin, M. Alexandre, L. & Giuliano, F. (2007). Supraspinal site of action for the inhibition of ejaculatory reflex by dapoxetine. European Urology, 51(3), 825-832. doi: Doi 10.1016/J.Eururo.2006.10.011
- ^ McMahon, C. G. Althof, S. E. Kaufman, J. M. Buvat, J. Levine, S. B. Aquilina, J. W. Porst, H. (2011). Efficacy and safety of dapoxetine for the treatment of premature ejaculation: integrated analysis of results from five phase 3 trials. [Meta-Analysis Research Support, Non-U.S. Gov’t]. J Sex Med, 8(2), 524-539. doi :10.1111/j.1743-6109.2010.02097.x PMID 21059176
- ^ Dapoxetine: a guide to its use in premature ejaculation (D. T. Perspective, Trans.). (2011) (Vol. 27, pp. 1-4).
- ^ Dresser, M. Lindert, K. Lin, D. Gidwani, S. Gupta, S. K. & Modi, N. B. (2004). Pharmacokinetics of single and multiple escalating doses of dapoxetine in healthy volunteers. Clinical Pharmacology & Therapeutics, 75(2), P32-P32. doi: Doi 10.1016/J.Clpt.2003.11.123
- ^ Kowey, P. R. Mudumbi, R. V. Aquilina, J. W. & DiBattiste, P. M. (2011). Cardiovascular safety profile of dapoxetine during the premarketing evaluation. [Research Support, Non-U.S. Gov’t]. Drugs R D, 11(1), 1-11. doi :10.2165/11587660-000000000-00000
- ^ Khan, A. Khan, S. Kolts, R. & Brown, W. A. (2003). Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: Analysis of FDA reports. American Journal of Psychiatry. 160(4), 790-792. doi: Doi 10.1176/Appi.Ajp.160.4.790
- ^ Tamam, L. & Ozpoyraz, N. (2002). Selective serotonin reuptake inhibitor discontinuation syndrome: A review. Advances in Therapy, 19(1), 17-26. doi: Doi 10.1007/Bf02850015
- ^ McMahon, C. G. (2012). Dapoxetine: a new option in the medical management of premature ejaculation. Ther Adv Urol, 4(5), 233-251. doi :10.1177/1756287212453866
- ^ ab Hellstrom WJ (2009). “Emerging treatments for premature ejaculation: focus on dapoxetine”. Neuropsychiatr Dis Treat. 5. 37вЂ“46. doi :10.2147/ndt.s3251. PMC 2695237 . PMID 19557098.
- ^ Owen RT (2009). “Dapoxetine: a novel treatment for premature ejaculation”. Drugs Today. 45 (9): 669вЂ“78. doi :10.1358/dot.2009.45.9.1388694. PMID 19956808.
- ^ Waldinger, M. D. (2007). Premature ejaculation вЂ” Definition and drug treatment. Drugs. 67(4), 547-568. doi: Doi 10.2165/00003495-200767040-00005.
- ^ Venkatesan, K. & Srinivasan, K. V. (2008). A stereoselective synthesis of (S )-dapoxetine starting from trans -cinnamyl alcohol. arkivoc, 16, 9.
- ^ Dapoxetine: LY 210448. (2005). [Review]. Drugs R D, 6(5), 307-311.
- ^ Priligy for Premature Ejaculation: Partnership with Menarini. (2012) Retrieved 11/17, 2012, from http://www.furiex.com/pipeline/marketed-products/priligy/
Premature ejaculation: dapoxetine
Key points from the evidence
Dapoxetine is a short-acting selective serotonin-reuptake inhibitor (SSRI). It is the first pharmacological treatment for premature ejaculation to be licensed in the UK. In a pooled analysis of 4 randomised controlled trials (RCTs) in men with premature ejaculation there was a statistically significant increase in intravaginal ejaculatory latency time (IELT) with dapoxetine ‘on demand’ compared with placebo ‘on demand’, although an increase in IELT was also seen with placebo.
Statistically significant increase in IELT from baseline with dapoxetine 30 mg and 60 mg ‘on demand’ compared with placebo ‘on demand’ (from 0.9 minutes in all groups to 1.9, 3.1 and 3.6 minutes respectively for placebo, dapoxetine 30 mg and dapoxetine 60 mg; p<0.001 for comparisons with placebo, pooled analysis of 4 RCTs, n=4843).
Statistically significantly more men reported that their premature ejaculation was ‘better’ or ‘much better’ with dapoxetine compared with placebo (30.7% and 38.3% with dapoxetine 30 mg and 60 mg respectively compared with 13.7% with placebo; p<0.001 for comparisons with placebo, pooled analysis of 4 RCTs, n=4843).
Orthostatic hypotension and syncope was reported in clinical trials and the summary of product characteristics includes recommendations to minimise the risk of this.
Treatment with dapoxetine should not be initiated with the 60 mg dose. The incidence and severity of adverse events is higher with the 60 mg dose.
Men will need to be appropriately assessed and given an accurate diagnosis of premature ejaculation in line with the indication in the summary of product characteristics before dapoxetine can be considered.
Dapoxetine is taken ‘on demand’ approximately 1 to 3 hours before anticipated sexual activity.
The summary of product characteristics states that dapoxetine should not be used in men taking phosphodiesterase type 5 inhibitors (for example, sildenafil).
The summary of product characteristics states that a careful appraisal of the individual benefit/risk ratio should be carried out after the first 4 weeks of treatment (or at least after 6 doses of treatment) with dapoxetine to determine whether continuing treatment is appropriate. If dapoxetine is continued the benefit/risk balance should be re-evaluated at least every 6 months.
Men will need to balance the potential benefits with the likelihood of very common (greater than 1 in 10 men) adverse reactions of dizziness, headache and nausea reported in the summary of product characteristics.
The cost of dapoxetine ranges from ВЈ14.71 for a pack of 3Г—30 mg tablets to ВЈ34.42 for a pack of 6Г—60 mg tablets.
The estimated cost of 30 days’ supply of a longer-acting SSRI taken daily (off-label use) ranges from ВЈ0.94 to ВЈ6.38 depending on the SSRI used and the dosage.
Introduction and current guidance
In the Diagnostic and Statistical Manual of Mental Disorders IV-Text Revision (DSM-IV-TR ), premature ejaculation is defined as a ‘persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it. The clinician must take into account factors that affect duration of the excitement phase, such as age, novelty of the sexual partner or situation, and recent frequency of sexual activity.’ The European Association of Urology 2014 guidelines on male sexual dysfunction state that although premature ejaculation is a very common male sexual dysfunction (with prevalence rates of 20% to 30%), the aetiology of premature ejaculation is unknown, with little data to support suggested biological and psychological hypotheses. Despite the possible serious psychological and quality of life consequences of premature ejaculation, few men seek treatment.
Dapoxetine (Priligy) is licensed in the UK for the ‘on demand’ treatment of premature ejaculation in adult men aged 18 to 64 years. The summary of product characteristics states that dapoxetine should only be prescribed to men who meet all the following criteria:
An intravaginal ejaculatory latency time (IELT) of less than 2 minutes and
Persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the man wishes and
Marked personal distress or interpersonal difficulty as a consequence of premature ejaculation and
Poor control over ejaculation and
A history of premature ejaculation in the majority of intercourse attempts over the prior 6 months.
The summary of product characteristics states that dapoxetine should not be prescribed to delay ejaculation in men who have not been diagnosed with premature ejaculation. The starting dose recommended in the summary of product characteristics for all men is 30 mg, taken as needed approximately 1 to 3 hours prior to sexual activity.
This evidence summary is based on a pooled analysis of results from 5 phase III RCTs (McMahon et al. 2011 ) in men with premature ejaculation; 4 of the RCTs contributed to the main efficacy outcome. These 4 RCTs (n=4843) compared dapoxetine 30 mg and 60 mg ‘on demand’ with placebo ‘on demand’ for IELT (defined as the duration of time from penetration to intravaginal ejaculation and measured by a stopwatch held by the female partner during each intercourse episode).
The pooled analysis showed that there was an increase from baseline in mean IELT at 12 weeks with all 3 groups including the placebo group. There was a statistically significantly greater increase from baseline in mean IELT at 12 weeks with both dapoxetine 30 mg and 60 mg ‘on demand’ compared with placebo ‘on demand’ (from 0.9 minutes in all groups to 1.9, 3.1 and 3.6 minutes respectively for placebo, dapoxetine 30 mg and dapoxetine 60 mg; p<0.001 for comparisons with placebo).
Pryor et al. (2006) concluded that the minimum clinically important change in IELT seems to be about 1 minute based on a correlation of global impression of change scores with mean changes in IELT. However, in clinical practice a minimum clinically important change in IELT has not been defined. In the pooled analysis, the improvement in mean 12-week IELT from baseline for the placebo group was 1 minute and the difference between placebo and dapoxetine 30 mg for the improvement in mean 12-week IELT was 1.2 minutes. In both the pooled analysis and the individual studies, the difference between dapoxetine 30 mg and 60 mg ‘on demand’ for the mean IELT at 12 weeks was less than 1 minute.
Very common (greater than 1 in 10 men) adverse reactions reported in the summary of product characteristics are dizziness, headache and nausea. Contraindications to the use of dapoxetine include significant pathological cardiac conditions such as heart failure, significant ischaemic heart disease or history of syncope; a history of mania or severe depression; moderate and severe hepatic impairment; and concomitant treatment with monoamine oxidase inhibitors, thioridazine, SSRIs, tricyclic antidepressants or other herbal/medicinal products with serotonergic effects and potent CYP3A4 inhibitors. The summary of product characteristics states that men should be advised not to use dapoxetine in combination with recreational drugs or alcohol. Treatment with dapoxetine should not be initiated with the 60 mg dose. If a man has an orthostatic reaction on the 30 mg dose, the dose should not be increased to 60 mg. For further information on contraindications, cautions and warnings please refer to the summary of product characteristics .
There are no RCTs that compare ‘on demand’ dapoxetine with an active comparator such as daily use of a longer-acting SSRI (off-label use). In addition, there are limited data available on the safety and efficacy of dapoxetine ‘on demand’ for longer than 24 weeks. The studies only included men aged 18 years and over (the average age in the pooled analysis was 41 years) in a monogamous heterosexual relationship for at least 6 months who met DSM-IV-TR criteria for premature ejaculation. The efficacy and safety of dapoxetine have not been established in men aged 65 years and over.
The European Association of Urology 2014 guidelines on male sexual dysfunction recommend that non-pharmacological treatments for premature ejaculation which are beneficial include psychosexual counselling, education, and behavioural treatments. Pharmacological treatment options for premature ejaculation include ‘on demand’ dapoxetine, daily use of a longer-acting SSRI (off-label use), daily use of clomipramine (off-label use), ‘on demand’ topical local anaesthetic agents (off-label use) or ‘on demand’ tramadol (off-label use).
Estimated impact for the NHS
The European Association of Urology 2014 guidelines on male sexual dysfunction state that in men for whom premature ejaculation causes few if any problems treatment should be limited to psychosexual counselling and education. For a number of men, pharmacological treatment of premature ejaculation will not be acceptable. Various behavioural techniques have demonstrated benefit in treating premature ejaculation and are indicated for men uncomfortable with pharmacological therapy. In lifelong premature ejaculation (onset from the first sexual experience and remaining during life), the European guidelines state that behavioural techniques are not recommended for first-line treatment because they are time-intensive, require the support of a partner and can be difficult to do. Pharmacotherapy is recommended as first-line therapy.
The summary of product characteristics for dapoxetine states that a careful appraisal of the individual benefit/risk ratio should be carried out after the first 4 weeks of treatment (or at least after 6 doses of treatment) with dapoxetine to determine whether continuing treatment is appropriate. If dapoxetine is continued the benefit/risk balance should be re-evaluated at least every 6 months.
Dapoxetine is the only medicine licensed in the UK for the treatment of premature ejaculation, although other treatments are used off-label for this indication. The General Medical Council advice to use a licensed medicine whenever possible should be taken into consideration.
About this evidence summary
‘Evidence summaries: new medicines’ provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.
Dapoxetine for premature ejaculation
Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer’s approved product information, a drug information centre or some other appropriate source.
Approved indication: premature ejaculation
Priligy (A Menarini)
30 mg tablets
Australian Medicines Handbook section 13.3.2
Delayed ejaculation is an adverse effect of selective serotonin reuptake inhibitors (SSRIs) in men. Dapoxetine, a short-acting SSRI, is the first drug to be marketed for premature ejaculation.
After oral administration, peak plasma concentrations of dapoxetine are reached after an hour. Elimination is relatively rapid and the terminal half-life is approximately 19 hours.
There have been several randomised controlled trials of dapoxetine for premature ejaculation. 1-6 The primary outcome for most of the trials was вЂintravaginal ejaculatory latency timeвЂ™ measured by the partner using a stopwatch.
An analysis of two trials, 1 in which 2614 men (aged 18вЂ“77 years) were randomised to dapoxetine (30 mg or 60 mg) or placebo (all taken 1вЂ“3 hours before intercourse), found that dapoxetine increased intravaginal ejaculatory latency time significantly more than placebo. At baseline, men were required to have an intravaginal ejaculatory latency time of 2 minutes or less at least 75% of the time. After 12 weeks, 29% of men taking the 30 mg dose and 34% taking the 60 mg dose had a latency time of 3 minutes or more. This was compared to only 14% of men taking placebo. Men taking dapoxetine perceived that they had better control of ejaculation and were more satisfied with their sexual performance than those taking placebo.
In another trial, dapoxetine (60 mg) was compared to paroxetine (20 mg), another SSRI, in 340 men (aged 22вЂ“48 years) with premature ejaculation. Treatments were taken each day divided into two doses. After 12 weeks, intravaginal ejaculatory latency times had increased from 38 to 179 seconds for dapoxetine, from 31 seconds to 370 seconds for paroxetine, and from 34 to 55 seconds for placebo. More men reported sexual satisfaction with dapoxetine and paroxetine than with placebo (66% vs 78% vs 16%). A similar trend in sexual satisfaction was seen with partners who were interviewed independently of their husband. Eleven men dropped out because of lack of efficacy вЂ“ 3/104 with dapoxetine, 2/105 with paroxetine and 6/100 with placebo. The timing of dosing in relation to sexual intercourse was not described in this trial. 6
During the trials, nausea (11%), headache (5.6%), diarrhoea (3.5%), somnolence (3.1%) and dizziness (5.8%) were more commonly reported with dapoxetine 30 mg than with placebo. These events were dose-related вЂ“ all of them were more frequent with the 60 mg dapoxetine dose. Nausea and dizziness were the most common reasons for discontinuation with dapoxetine 30 mg. Because of the increased risk of adverse events, patients should be warned to take no more than one tablet in a 24-hour period.
Sexual adverse effects including erectile dysfunction, abnormal ejaculation and decreased libido were more common with dapoxetine than placebo. These occurred in 2.9% of patients taking dapoxetine 30 mg and 3.8% taking dapoxetine 60 mg versus 1.5% of patients taking placebo. 1
Postural hypotension occurred in some patients and caution is urged with concomitant use of vasodilators such as alpha blockers, nitrates and phosphodiesterase 5 inhibitors. Syncope has been reported with dapoxetine and appeared to be dose-related (0.05% with placebo, 0.06% with 30 mg and 0.23% with 60 mg dose). Possible prodromal symptoms such as nausea, dizziness and light-headedness were also more common with dapoxetine than with placebo. Patients should be warned about this risk and advised to maintain adequate hydration and avoid alcohol.
Dapoxetine is metabolised by enzymes in the liver and kidneys, in particular cytochrome P450 (CYP) 2D6 and 3A4. It also moderately inhibits CYP 2D6 and weakly induces CYP 3A4 so numerous interactions are expected. Poor CYP 2D6 metabolisers may be at increased risk of adverse events. Concomitant treatment with potent CYP 3A4 inhibitors such as ketoconazole and ritonavir is contraindicated. Dapoxetine is also contraindicated with antidepressants including monoamine oxidase inhibitors, serotonin reuptake inhibitors, tricyclics and other drugs with serotonergic effects (tramadol, St JohnвЂ™s wort and lithium).
Dapoxetine should not be taken in combination with recreational drugs such as ketamine, methylenedioxymethamphetamine (MDMA) and lysergic acid diethylamide (LSD) because of the potential risk of serious adverse events including arrhythmia, hyperthermia and serotonin syndrome. Concomitant sedatives can increase the risk of somnolence and dizziness.
Dapoxetine is contraindicated in patients with heart problems such as heart failure, conduction abnormalities or significant ischaemic or valvular disease. It is also contraindicated in moderate and severe hepatic impairment. Dapoxetine is not recommended in patients with severe renal impairment or with psychiatric disorders.
Although dapoxetine prolongs intravaginal latency time before ejaculation, improvements seem modest and a placebo effect was apparent in most of the studies. In an analysis of two trials, mean latency time increased from an average of 0.9 minutes at baseline to 1.75 minutes with placebo and 2.78 minutes with dapoxetine (30 mg taken on-demand). 1 In a comparative trial, paroxetine was more effective than dapoxetine, although it was unclear when treatment was taken in relation to sexual intercourse. This may have affected efficacy. 6 The benefits and adverse effects of dapoxetine treatment should be reviewed after four weeks (or six doses).
В© 2016 NPS MedicineWise. Providing independent, evidence based information for the Australian Capital Territory (ACT), New South Wales, Northern Territory, Queensland, South Australia, Tasmania, Victoria and Western Australia.
PO Box 1147 Strawberry Hills NSW 2012 Level 7, 418A Elizabeth St, Surry Hills NSW 2010 ABN: 61 082 034 393 HONcode
xenical en suisse
ASHFORD CRJ 305 Entire Course (Crime Prevention)
xenical efekty uboczne
xenical preparat za mrsavljenje
tem generico do xenical
learn more here
click to see more
check this out
buy your dissertation online
click the following article