Brand Name: Prolong-30

Generic Name: Dapoxetine HCl

Strength: 30 mg

Dosage Form: Tablets

Class of Drug: SSRI 

 Indication:

• Premature Ejaculation (PE)

Mechanism of Action  

The mechanism of action of Dapoxetine in premature ejaculation is presumed to be linked to the inhibition of neuronal reuptake of serotonin and the subsequent potentiation of the neurotransmitter's action at pre- and postsynaptic receptors.

 Pharmacokinetics: 

Absorption

Dapoxetine is rapidly absorbed with maximum plasma concentrations (C_max) occurring approximately 1-2 hours after tablet intake. The absolute bioavailability is 42% (range 15-76%), and dose proportional increases in exposure (AUC and C_max) are observed between the 30 and 60 mg dose strengths.

Distribution

More than 99% of dapoxetine is bound in vitro to human serum proteins. The active metabolite desmethyldapoxetine (DED) is 98.5% protein bound. Dapoxetine has a mean steady state volume of distribution of 162 L.

Biotransformation

In vitro studies suggest that dapoxetine is cleared by multiple enzyme systems in the liver and kidneys, primarily CYP2D6, CYP3A4, and flavin monooxygenase (FMO1). Following oral dosing of ¹⁴C-dapoxetine, dapoxetine was extensively metabolized to multiple metabolites primarily through the following biotransformational pathways: N-oxidation, N-demethylation, naphthyl hydroxylation, glucuronidation and sulfation. There was evidence of presystemic first-pass metabolism after oral administration.

Intact dapoxetine and dapoxetine-N-oxide were the major circulating moieties in the plasma. In vitro binding and transporter studies show that dapoxetine-N-oxide is inactive. Additional metabolites including desmethyldapoxetine and didesmethyldapoxetine account for less than 3% of the total circulating drug –related materials in plasma. In vitro binding studies indicate that DED is equipotent to dapoxetine and didesmethyldapoxetine has approximately 50% of the potency of dapoxetine (see section 5.1). The unbound exposures (AUC and C_max) of DED are approximately 50% and 23%, respectively, of the unbound exposure of dapoxetine.

Elimination

The metabolites of dapoxetine were primarily eliminated in the urine as conjugates. Unchanged active substance was not detected in the urine. Following oral administration, dapoxetine has an initial (disposition) half-life of approximately 1.5 hours, with plasma levels less than 5% of peak concentrations by 24 hours post-dose, and a terminal half-life of approximately 19 hours. The terminal half-life of DED is approximately 19 hours.

 Dosage:

30 mg OD, 1-3 hours before sexual intercourse.

3 days a week, for 3 months.

Dose can be increased to 60 mg in consultation with Doctors.

It can be taken with or without food.

Adverse Drug Reactions: 

The following adverse drug reactions were reported during Phase 3 clinical trials most commonly and were dose related: nausea, dizziness, headache, diarrhoea, insomnia and fatigue.  

Fertility, Pregnancy and Lactation: 

It is not indicated for use by women.

Animal studies do not indicate direct or indirect harmful effects with respect to fertility, pregnancy or embryonal/foetal development .

 Presentation: 5 x 1 x 3 Tablets