Dapoxetine

Structural formula
General
Non-proprietary name	Dapoxetine
other names	(+) - N , N -dimethyl-1-phenyl-3- (1-naphthyloxy) propylamine ( S ) - N , N -Dimethyl-1-phenyl-3- (1-naphthyloxy) propylamine
Molecular formula	C 21 H 23 NO (dapoxetine) C 21 H 24 ClNO (dapoxetine hydrochloride )
External identifiers / databases
CAS number 119356-77-3 (dapoxetine) 129938-20-1 (dapoxetine hydrochloride) PubChem 71353 ChemSpider 64453 DrugBank DB04884 Wikidata Q424965
Drug information
ATC code	G04 BX14
Drug class	Serotonin reuptake inhibitors
Mechanism of action	Inhibition of serotonin reuptake
properties
Molar mass	305.41 g · mol -1 (dapoxetine) 341.87 g · mol -1 (dapoxetine · hydrochloride)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 302-319-413 P: 305 + 351 + 338
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Dapoxetine (trade name Priligy , manufacturer Janssen-Cilag ), Sales now by Berlin-Chemie ( Menarini ) is a drug that since April 2009 in Germany for oral treatment of premature ejaculation ( premature ejaculation of the man is allowed). Based on the studies to date, a three to four-fold increase in the intravaginal latency period of ejaculation can be assumed. In addition, dapoxetine can improve sexual satisfaction and perceived control over ejaculation in men and reduce psychological stress and interpersonal difficulties.

Since it is legally a lifestyle drug , the costs are not covered by the German health insurance companies.

application areas

According to the Package Leaflet (GI), dapoxetine is indicated for the treatment of premature ejaculation (ejaculatio praecox, EP) in adult men aged 18 to 64 years. Dapoxetine should only be prescribed to patients who meet the following criteria:

• an intravaginal latency time to ejaculation (English: intravaginal ejaculation latency time (IELT)) of less than two minutes; and
• persistent or recurrent ejaculation with minimal sexual stimulation before, during, or shortly after penetration and sooner than the patient wishes; and
• clear personal pressure of suffering or interpersonal problems as a result of EP; and
• insufficient control over ejaculation; and
• a history of premature ejaculation in most sex attempts during the previous six months.

Dapoxetine should only be used as reliever medication prior to expected sexual activity. Dapoxetine should not be prescribed to men to delay ejaculation without a prior diagnosis of EP.

Mechanism of action

The ejaculation reflex represents a complex interplay between physical mechanisms in the central nervous system and here especially in the spinal cord . The messenger substance serotonin plays a central, inhibiting role in this structure for ejaculation. The active ingredient dapoxetine belongs to a group of antidepressants , specifically the serotonin reuptake inhibitors (SSRI) . So it blocks the serotonin transporter , which removes the serotonin from its place of action and thus leads to a longer retention time of serotonin on certain nerve fibers in the brain and thus presumably to a delay in ejaculation.

Risks and Side Effects

The tolerability and safety of dapoxetine was investigated in 4,224 patients in five placebo-controlled studies. The most commonly reported adverse drug reactions (ADRs) with the use of dapoxetine in phase III clinical studies were: nausea, dizziness, headache, diarrhea, insomnia and fatigue.

The most common side effects that led to discontinuation of dapoxetine were: nausea (2.2% of the treated subjects) and dizziness (1.2% of the subjects).

Syncope (loss of consciousness) and orthostatic hypotension

Syncope related to the use of dapoxetine occurred in 0.06 to 0.23% in the phase III studies. This is a brief sudden loss of consciousness with simultaneous failure of the holding tone (risk of falling) and subsequent spontaneous recovery. In none of the reported cases there was an acceleration or arrhythmia of the heartbeat. The majority of cases occurred in the first three hours after taking dapoxetine, after the first dose, or in connection with study-related measures in a clinical setting (such as blood draws and orthostatic maneuvers and blood pressure measurements). Syncope is often announced by nausea, dizziness, drowsiness, etc. after taking dapoxetine. The frequency of syncope can be significantly reduced by taking dapoxetine with a large glass of water. Symptoms similar to those of syncope can occur with so-called orthostatic hypotension (drop in blood pressure after getting up from a sitting or lying position). These symptoms have been reported in <1% of patients treated with dapoxetine. Patients prescribed dapoxetine should be advised of the possibility of syncope or orthostatic hypotension. Work on machines and participation in road traffic should be suspended while taking dapoxetine.

Contraindications

According to the Instructions for Use (GI), men should not be treated with dapoxetine if any of the following applies:

• Heart disease ( heart failure), conduction disorders (second or third degree AV block or sick sinus syndrome), ischemia of the heart (lack of oxygen, such as occurs in CHD ), heart valve disease, history of syncope.
• Mania or depression
• Moderate to severe liver dysfunction.
• concomitant treatment with an MAOI (or ingestion within the last 14 days; MAOI should not be administered within 7 days of stopping dapoxetine). Monoamine oxidase inhibitors are drugs that are used to treat depression.
• concomitant treatment with thioridazine (or ingestion within the last 14 days; thioridazine should not be administered within 7 days of stopping dapoxetine). Thioridazine belongs to the group of psychotropic drugs and acts as a neuroleptic .
• Simultaneous (or within the last 14 days) treatment with: serotonin reuptake inhibitors ( SSRI ), serotonin norepinephrine reuptake inhibitors ( SNRI ), tricyclic antidepressants (TCA) and other medicinal products / herbal ingredients with serotonin-enhancing (serontonin-enhancing) effects (e.g. B. L -Tryptophan, Triptans, Tramadol, Linezolid, Lithium, St. John's Wort). The active substances mentioned should not be administered within 7 days of stopping dapoxetine.
• Concomitant therapy with highly effective isoenzyme inhibitors ( CYP3A4 inhibitors), such as ketoconazole , itraconazole , ritonavir , cobicistat , saquinavir , telithromycin , nefazadone , nelfinavir or atazanavir .

criticism

According to arznei-telegramm (at) , dapoxetine, taken when needed, increases the time to ejaculation by around one minute on average compared to placebo. This does not correspond to the values ​​given in the product information. The at advises against the use of the poorly effective and expensive SSRI. In 2009, the benefits and safety were not proven for any of the therapeutic measures available for ejaculation praecox.

The European Medicines Agency (EMA) has entered into arbitration to approve Priligy tablets due to disagreements within the member states of the European Union (EU). The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of the 60 mg tablets (overriding disagreement) outweigh the risks and that Priligy's marketing authorization given in Sweden is recognized in other EU Member States can .

Tablets, pack sizes

Priligy ^® requires a prescription and is available on the market in doses of 30 mg and 60 mg as an oral film- coated tablet. Pack sizes of 3 and 6 film-coated tablets each are available.

Web links

• European Medicines Agency information document (PDF)
• Rating (infomed)
• Evaluation ( drug telegram )

Individual evidence

1. ↑ ^{a b} Data sheet Dapoxetine hydrochloride from Sigma-Aldrich , accessed on March 24, 2011 ( PDF ).
2. ↑ http://www.janssen-cilag.com/content/news/janssen-cilag.de_ger/local_content/news_product_90.pdf
3. ↑ ^{a b c} Instructions for use of Priligy ^® 30 mg  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. (PDF; 770 kB), (as of January 2013).  
4. ↑ ^{a b c} Instructions for use for Priligy ^® 60 mg  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. (PDF; 770 kB), (as of January 2013).  
5. ↑ ^{a b c} Berlin-Chemie: Fachinformation Priligy ^®  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. (PDF; 147 kB), as of January 2013.  
6. ↑ ^{a b c} McMahon CG et al .: Efficacy and Safety of Dapoxetine for the Treatment of Premature Ejaculation: Integrated Analysis of Results from Five Phase 3 Trials . In: The Journal of Sexual Medicine . tape 8 , no. 2 , February 2011, p. 524-539 , doi : 10.1111 / j.1743-6109.2010.02097.x .
7. ^ Resolution of the Federal Joint Committee on an amendment to the Medicines Directive (AM-RL): Annex II - Lifestyle Medicines (PDF; 288 kB), April 15, 2010.
8. ↑ infomed.ch: Dapoxetin - pharma-kritik - Infomed Online , accessed on February 16, 2017
9. ↑ Hans-Ulrich Schmelz, Christoph Sparwasser, Wolfgang Weidner: Specialist knowledge of urology, differentiated diagnostics and therapy . Springer-Verlag, 2011, ISBN 978-3-642-01626-4 , pp. 773 ( limited preview in Google Book search).
10. ↑ New on the market , evaluation of arznei-telegramm (at) in 2009.
11. ↑ EMA / CHMP / 842278/2011 Rev. 1 (PDF; 48 kB), questions and answers on Priligy (dapoxetine, 30 mg and 60 mg tablets) (as of January 2012).

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !