Dapoxetine Hydrochloride is used for the treatment of premature ejaculation (PE) in men aged 18 to 64 years who experience one or more of the following conditions:

• Persistent or repeated ejaculation occurring with minimal sexual stimulation, either before, during, or shortly after penetration, and earlier than desired by the patient.
• Significant personal distress or difficulty in interpersonal relationships due to premature ejaculation.
• Reduced or poor control over ejaculation timing.

The mechanism of action of Dapoxetine in treating premature ejaculation is believed to involve inhibition of the neuronal reuptake of serotonin, which enhances serotonin activity at both pre-synaptic and post-synaptic receptors. Ejaculation in humans is mainly controlled by the sympathetic nervous system. The ejaculatory process begins from a spinal reflex center, which is regulated by the brain stem and influenced by several brain nuclei, including the medial preoptic and paraventricular nuclei.

After oral administration, Dapoxetine is rapidly absorbed, reaching maximum plasma concentration (Cmax) within about 1–2 hours. Its absolute bioavailability is approximately 42%. More than 99% of Dapoxetine binds to human serum proteins in vitro. The active metabolite, Desmethyl Dapoxetine (DED), is about 98.5% protein bound. The drug shows rapid distribution, with a mean steady-state volume of distribution of around 162 liters.

Dapoxetine undergoes extensive metabolism into multiple metabolites through several pathways, including N-oxidation, N-demethylation, naphthyl hydroxylation, glucuronidation, and sulfation. There is evidence of significant first-pass (presystemic) metabolism after oral intake. The metabolites are mainly excreted in urine as conjugated forms. Dapoxetine is eliminated quickly, with a terminal half-life of approximately 19 hours.

For Premature Ejaculation:

Adult men (18 to 64 years of age): The recommended starting dose for all patients is 30 mg, taken as needed approximately 1 to 3 hours prior to sexual activity. The maximum recommended dosing frequency is once every 24 hours. If the effect of 30 mg is insufficient and the side effects are acceptable, the dose may be increased to the maximum recommended dose of 60 mg. Dapoxetine may be taken with or without food.

Children and adolescents: Dapoxetine should not be used in individuals below 18 years of age. Elderly (age 65 years and over): Safety and efficacy of Dapoxetine have not been established in patients age 65 years and over as limited data are available in this population.

Patients with renal impairment: Caution is advised in patients with mild or moderate renal impairment. Dapoxetine is not recommended for use in patients with severe renal impairment.

Patients with hepatic impairment: Dapoxetine is contraindicated in patients with moderate and severe hepatic impairment

CNS-active medicinal products: The combined use of Dapoxetine Hydrochloride with other centrally acting (CNS-active) medicines has not been thoroughly studied in patients with premature ejaculation. Therefore, caution is recommended when these medicines are used together with Dapoxetine.

PDE5 inhibitors: Tadalafil does not significantly affect the pharmacokinetics of Dapoxetine. Sildenafil may cause minor changes in Dapoxetine pharmacokinetics, but these are not considered clinically important. However, Dapoxetine should still be used carefully in patients taking PDE5 inhibitors due to a possible reduction in orthostatic tolerance.

Tamsulosin: The use of single or repeated doses of Dapoxetine (30 mg or 60 mg) together with daily Tamsulosin did not significantly change Tamsulosin pharmacokinetics. However, caution is advised when Dapoxetine is used alongside alpha-adrenergic receptor antagonists because of a potential decrease in orthostatic tolerance.

Warfarin: There is no available data on the long-term combined use of Warfarin and Dapoxetine. Therefore, caution is recommended when prescribing Dapoxetine to patients on chronic Warfarin therapy.

Ethanol (Alcohol): Taking alcohol together with Dapoxetine may increase the risk or severity of side effects such as dizziness, drowsiness, delayed reflexes, and impaired judgment. This combination may also enhance alcohol-related effects and increase neurocardiogenic reactions such as fainting (syncope), raising the risk of accidental injury. Patients are therefore advised to avoid alcohol while using Dapoxetine.

• Patients with known hypersensitivity to Dapoxetine Hydrochloride.
• Patients with significant pathological cardiac conditions such as:
  • Heart failure (NYHA class II–IV)
  • Conduction abnormalities (second- or third-degree AV block, sick sinus syndrome) not treated with a permanent pacemaker
  • Significant ischemic heart disease
  • Significant valvular heart disease
• Concomitant use with monoamine oxidase inhibitors (MAOIs) or thioridazine, or within 14 days of stopping these drugs.
• MAOIs or thioridazine should not be started within 7 days after stopping Dapoxetine.
• Concomitant use with serotonin reuptake inhibitors (SSRIs, SNRIs, TCAs) or other serotonergic medicines or herbal products, or within 14 days of stopping them.

The most common side effects of Dapoxetine Hydrochloride include nausea, dizziness, dry mouth, headache, diarrhea, and insomnia. Discontinuation of treatment due to adverse effects is dose-related. In clinical studies involving 1067 subjects, the discontinuation rates were 0.3% with placebo, 1.7% with Dapoxetine 30 mg, and 5.3% with Dapoxetine 60 mg. Unlike other SSRIs used for depression, which are often associated with a high incidence of sexual dysfunction, Dapoxetine is linked with a low rate of such side effects. When taken as needed, it shows very mild sexual adverse effects, including decreased libido in less than 1% of users and erectile dysfunction in less than 4% of users.

Dapoxetine Hydrochloride is not recommended for use in women. It is also unknown whether Dapoxetine or its metabolites are excreted in human breast milk.

Use with recreational drugs:
Patients should be warned not to take Dapoxetine together with recreational drugs. Drugs with serotonergic effects such as ketamine, methylenedioxymethamphetamine (MDMA), and lysergic acid diethylamide (LSD) may cause serious and potentially dangerous reactions when used with Dapoxetine. These may include, but are not limited to, irregular heartbeat (arrhythmia), elevated body temperature (hyperthermia), and serotonin syndrome.

Using Dapoxetine with sedative recreational substances such as narcotics or benzodiazepines may further increase drowsiness and dizziness.

Ethanol (Alcohol):
Taking alcohol with Dapoxetine may intensify alcohol-related effects on cognition and also increase the risk of neurocardiogenic adverse effects such as fainting (syncope). This can raise the chance of accidental injury. Therefore, patients should avoid alcohol during Dapoxetine treatment.

Syncope (fainting):
Early warning symptoms such as nausea, dizziness, lightheadedness, palpitations, weakness (asthenia), confusion, and sweating (diaphoresis) usually occur within 3 hours after taking the dose and may precede fainting. Patients should be informed that fainting can occur at any time during treatment, with or without warning signs.

Orthostatic hypotension:
An orthostatic test should be carried out before starting treatment. If there is a history or suspicion of orthostatic hypotension, Dapoxetine should not be used.

Bleeding risk:
Bleeding abnormalities have been reported with SSRIs. Caution is required when Dapoxetine is used, especially alongside medicines that affect platelet function (such as atypical antipsychotics, phenothiazines, aspirin, NSAIDs, and anti-platelet drugs) or anticoagulants (e.g., warfarin). Extra caution is also needed in patients with a history of bleeding or clotting disorders.

PDE5 inhibitors:
A single-dose crossover study evaluated Dapoxetine (60 mg) with Tadalafil (20 mg) and Sildenafil (100 mg). Neither Tadalafil nor Sildenafil altered the pharmacokinetics of Dapoxetine.

Tamsulosin:
Dapoxetine should be used carefully in patients taking alpha-adrenergic receptor blockers due to a possible reduction in tolerance to orthostatic changes in blood pressure.

Overdose:
No cases of Dapoxetine overdose have been reported. In a clinical pharmacology study, daily doses up to 240 mg (given as two 120 mg doses taken 3 hours apart) did not show any unexpected adverse effects.

In general, SSRI overdose may cause serotonin-related symptoms such as drowsiness, gastrointestinal disturbances (including nausea and vomiting), rapid heart rate (tachycardia), tremors, restlessness or agitation, and dizziness.

Withdrawal effects:
A clinical trial in patients with premature ejaculation (PE) evaluated the effects of 62 days of daily or on-demand use of 60 mg Dapoxetine. The study found no evidence of withdrawal syndrome after stopping the medication.

Drugs for Erectile Dysfunction

Store at a temperature below 30°C. Keep the product protected from light and moisture. Ensure it is stored safely out of the reach of children.