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Dapoxetine

Well Researched

Short-acting on-demand SSRI | First and only PE-specific drug approved in 60+ countries (not FDA-approved)

Aliases (7)
Priligy · dapoxetine hydrochloride · LY-210448 · Poxet · Duralast · Dapsule · Westoxetin
TYPICAL DOSE
30-60 mg PRN
PRN — not daily
ROUTE
Oral (tablet)
Oral tablet, swallowed whole with water
CYCLE
On-demand only — not chronic
On-demand only by design; no chronic dosing rationale
STORAGE
Room temp; original blister
Room temperature in original blister

Overview

What is Dapoxetine?

Dapoxetine (Priligy, LY-210448) is the first and only SSRI specifically developed and approved for premature ejaculation. Approved in the EU/UK/Australia/Canada/India and 60+ other countries between 2009 and 2017 for on-demand use in men 18-64 with PE. Originally developed by Eli Lilly as an antidepressant; the NDA was withdrawn in the US in 2005 for commercial reasons before re-positioning as a PE-specific agent — never re-submitted to FDA by subsequent owners (ALZA → Janssen → Menarini).

Key Benefits

On-demand SSRI taken 1-3 hours before sex extends IELT roughly 2.5-3.0x over placebo (geometric mean 0.9 to 3.1-3.6 minutes in pivotal phase III pooled analyses). Designed for short systemic exposure: rapid Tmax ~1-2 h, fast alpha-phase elimination (t½ ~1.5 h) with minimal accumulation — sidesteps the chronic-SSRI side-effect profile that plagues off-label paroxetine/sertraline/fluoxetine use for PE. Works first dose; no titration period; well-tolerated for an SSRI.

Mechanism of Action

SERT inhibition at the spinal ejaculatory generator raises 5-HT tone at the lumbar sympathetic outflow, increasing the ejaculatory reflex threshold. Dapoxetine's chemistry was deliberately tuned for fast absorption and rapid alpha-phase clearance so the serotonergic effect lasts roughly the duration of a sexual encounter rather than 24+ hours like classical SSRIs.

Pharmacokinetics

·
PeakHalf-life
Approximate curve — visual aid only, not data-precise PK

Peptide Interactions

Sildenafil / Tadalafil / Vardenafil
Synergistic

(PDE5 inhibitors): Dapoxetine extends IELT, PDE5i ensures erection quality. Co-use for PE + mild ED is well-studied and recommended in some EU guidelines. No…

Behavioral techniques
Synergistic

(start-stop, squeeze, pelvic floor strengthening): Pharmacological + behavioral combination outperforms drug alone across trials.

Topical lidocaine/prilocaine sprays
Synergistic

(on glans): Different mechanism (peripheral desensitization vs central serotonin); can layer for non-responders. Note: condom use protects partner from numbi…

MAOIs
Avoid

(phenelzine, tranylcypromine, linezolid, methylene blue, selegiline >10 mg/d): Absolute contraindication. 14-day washout each direction. Risk of fatal seroto…

Other SSRIs / SNRIs / TCAs
Avoid

Additive serotonergic load. If the user is already on a chronic SSRI for any indication, do not add dapoxetine — washout first.

Tramadol, meperidine, MDMA, mephedrone
Avoid

Serotonergic stacking; serotonin syndrome risk.

5-HTP, L-tryptophan, St John's Wort
Avoid

Same serotonergic concern.

Strong CYP3A4 inhibitors
Avoid

(ketoconazole, ritonavir, clarithromycin, telithromycin, nefazodone): Raise dapoxetine AUC ~2x → increased syncope/orthostatic risk. EU label contraindicates…

Alcohol
Avoid

Amplifies dizziness, syncope, CNS depression. EU label warns against combined use.

Recreational stimulants (MDMA, mephedrone, cocaine)
Avoid

Avoid; serotonergic + cardiovascular load.

Thioridazine
Avoid

(CYP2D6 substrate with QT effects): Contraindicated.

PDE5 inhibitors
Compatible

as noted (synergistic for combined PE + ED).

Quality Indicators

Pharmacy-dispensed Priligy in original blister (EU/UK/AU/CA)

Janssen-licensed Priligy 30 mg or 60 mg in foil blister with batch + expiry. The cleanest sourcing path where legally available.

Indian generics (Sun Pharma, Cipla, Menarini-licensed)

Brand names: Poxet (Sun), Duralast, Dapsule, Westoxetin. WHO-GMP manufacturers; same gray-market sourcing channel as modafinil generics.

!

Fixed-dose combos with sildenafil/tadalafil

Indian market sells "Super Tadarise", "Super P-Force", etc. — dapoxetine 60 mg + sildenafil/tadalafil. Convenient but harder to titrate each component. Prefer separate dosing on first use.

Non-blister 'natural' pills claiming PE benefit

FDA seizes counterfeit supplements adulterated with undeclared dapoxetine + sildenafil. Avoid any "all-natural PE" supplement — assume hidden pharma.

US compounding pharmacy dapoxetine

Dapoxetine is not on FDA's approved or pre-approved bulk substances lists; legitimate US compounding is not legal. Any US compounding source is problematic.

What to Expect

  • Onset
    1-2 hours. Most men report a noticeable shift in ejaculatory threshold by the 90-minute mark.
  • Peak
    window: Hour 1.5 to hour 4. Effect on IELT is robust here.

Side Effects & Safety 8

Side Effects

  1. 1Nausea — ~10-22% across trials (dose-dependent: 30 mg lower, 60 mg higher). First-dose worst; food + hydration help.
  2. 2Dizziness — ~6-11%. Worst on first dose, often diminishes with subsequent use.
  3. 3Headache — ~6-9%.
  4. 4Diarrhea / GI upset — ~4-7%.
  5. 5Insomnia / vivid dreams (atypical for an SSRI but reported)
  6. 6Dry mouth, sweating, fatigue
  7. 7Mild blurred vision
  8. 8Light-headedness, particularly orthostatic

When to Stop

  • Syncope / vasovagal-type response — the unusual signal in dapoxetine trials. ~0.3-1.5% in phase III. Mechanism likely vagal/orthostatic; presents as feeling faint, dropping BP, occasionally losing consciousness briefly. Almost always first-dose or first-few-doses; resolves with hydration and rest. EU label requires a syncope warning. Take first dose seated/lying down for the first hour.
  • Serotonin syndrome — when stacked with other serotonergic drugs (MAOIs, SSRIs, SNRIs, TCAs, tramadol, MDMA, 5-HTP, St John's Wort). Cardinal triad: autonomic instability, neuromuscular hyperactivity (clonus, hyperreflexia), altered mental status. Medical emergency.
  • Mood changes — anxiety, depression, suicidal ideation reported but not class-typical at PRN exposure. EU label includes the SSRI-class suicidality precaution.
  • Mania/hypomania — bipolar diagnosis is a hard contraindication.
  • Hepatic effects — rare elevation of LFTs; not used in moderate-severe hepatic impairment.
  • First dose: Highest syncope risk. Sit or lie down for the first 60-90 minutes; have water nearby; avoid hot showers, alcohol, or other vasodilators that day.
  • First 6 doses: Refine dose (30 vs 60 mg) and timing (1 h vs 2 h vs 3 h pre-activity).
  • Any switch from chronic SSRI: Mandatory washout — 1-2 weeks for sertraline/escitalopram/paroxetine, 5-6 weeks for fluoxetine because of the long norfluoxetine tail.

References

PMID 17011944

pubmed.ncbi.nlm.nih.gov · 2006

Pryor 2006 Lancet phase III pivotal pooled analysis (~2,600 men).

View Study

PMID 22247794

pubmed.ncbi.nlm.nih.gov · 2011

McMahon 2011 integrated 5-trial analysis (~6,000 men).

View Study

PMID 21696550

pubmed.ncbi.nlm.nih.gov · 2012

McMahon 2012 J Sex Med pooled phase III analysis.

View Study

PMID 24433890

pubmed.ncbi.nlm.nih.gov · 2014

Mirone 2014 PAUSE study real-world cohort (~6,700 men).

View Study

PMID 16855071

pubmed.ncbi.nlm.nih.gov · 2006

Modi 2006 dapoxetine PK characterization (Tmax, alpha/beta t½).

View Study
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