Dapoxetine

Mechanism of action:

• Dapoxetine is a potent selective serotonin reuptake inhibitor (SSRI) with IC50 at 1.12 nm, while its major human metabolites, desmethyldapoxetine (IC50 <1.0 nM) and didesmethyldapoxetine (IC50 = 2.0 nM) are equivalent or low-potency (POPE). (IC50 = 282 nM)).
• Human ejaculation is primarily mediated by the sympathetic nervous system. The ejaculation pathway arises from a spinal reflex center, mediated by the stem of the brain, which is initially affected by multiple nuclei in the brain (medial prophylactic and paraventricular nuclei).
• The mechanism of action of dapoxinate in premature ejaculation is thought to be associated with the inhibition of neuronal burst of serotonin and subsequent potentiation of neurotransmitters at pre- and postsynaptic receptors.

Pharmacokinetics:

• Dapoxetine is a white powdered substance and water-insoluble. Taken 1-3 hours before sexual activity, it is rapidly absorbed into the body. Its maximum plasma concentration (Cmax) is reached within 1-2 hours after oral administration. Cmax and AUC (area under plasma vs. time curve) are dose dependent. Cmax and TM (the time required to achieve maximum plasma concentration) are 297 and 498 ng / ml 1.01 and 1.27 hours, respectively, after single doses of demaxitine 30 mg and 60 mg. High-fat food reduces Cmax slightly, but is negligible. In fact, food does not alter dapoxetine pharmacokinetics. It can be taken with or without food.
• Distribution: Dapoxetine is absorbed and rapidly distributed throughout the body. More than 99% of daphoxin is bound to plasma proteins. The average steady-state volume is 162 L. Its initial half-lives are 1.31 hours (30 mg dose) and 1.42 hours (60 mg dose), and its terminal half-lives are 18.7 hours (30 mg dose) and 21.9 hours (60 mg dose).
• Metabolism: Dapoxetine is extensively metabolized in liver and kidney, such as CYP2D6, CYP3A4, and flavin monooxygenase. The major product at the end of the metabolic pathway is circulating Dapoxetine N-oxide, which is a weak SSRI and has no contribution in clinical effect. Other products presented less than 3% in plasma are desmethyldapoxitin and daemmethidapoxetine. Desmethyldapoxitin is almost identical to dapoxetine.
• Excretion: Metabolites of dapoxetine are rapidly eliminated in the urine with a terminal half-life of 18.7 and 21.9 hours for a single dose of 30.7 mg and 60 mg, respectively.

Pharmacodynamics:

• Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor. The physiology of ejaculation mainly depends on serotonin and dopamine receptors, including 5-HT1a and 5-HT2c. Dapoxetine hydrochloride prevents bursting of the serotonin transporter. The drug binds with reuptake transporters of norepinephrine and dopamine and inhibits reuptake.

Precautions:

• Dapoxetine should not be used:

Patients are allergic to its contents.

Patients suffering from kidney disease or dialysis.

Patients suffering from liver diseases

Patients with heart problems (heart failure, irregular heart rate, valvular heart disease)

Patients with bleeding disorders

History of syncope (syncope)

History of severe depression

Tour history

Serious alcoholics

Side effects:

• Side effects are possible but do not always occur in all patients.

Some of the commonly observed side effects may include:

head ache

Dizziness

Sleepiness

Tremors of earthquake

Difficulty sleeping

Nausea

Loss of libido

Diarrhea

dry mouth

Dosage:

• For Premature Ejaculation and Erectile Dysfunction (Adult):
• The recommended adult dose of dapoxetine hydrochloride is 30 – 60 mg / day. The maximum dose should not exceed 100 mg / day. Take dapoxetine hydrochloride at least two hours before sexual intercourse to get maximum treatment benefits.

Overdosage:

There have been no reported cases of drug overdose during clinical trials.

Warning:

• This tablet can make you faint. You may experience warning symptoms such as nausea, dizziness or mild sadness before you faint. Unless you feel nauseous, dizzy or light-headed, until the symptoms pass, lie on your head or sit between your knees. This will prevent falls and injury.
• Do not take more than one tablet once every 24 hours due to the risk of syncope.

Duration of actions:

Dapoxetine is a short acting SSRI and doses of 30 mg and 60 mg have been evaluated through our meta-analysis. Peak plasma concentrations of dapoxetine were observed within 1.01–2.27 hours after oral administration 24. The elimination half-life time is 1.3–1.4 hours and there appears to be very little accumulation.

Drug- drug interactions:

• With phosphodiesterase inhibitors (PDE5 inhibitors): Many people who have PE also suffer from erectile dysfunction (ED). Treatment for these patients should consider drug-drug interactions between dapoxetine and PDE5 inhibitors such as tadalafil or sildenafil. In the Dresser study (2006), plasma concentrations of 24 subjects were obtained. Half of the sample pools 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 analyzed using liquid chromatography – tandem mass spectrometry. The results showed that dapoxetine does not alter the pharmacokinetic of tadalafil or sildenafil.
• With ethanol: Ethanol does not affect the pharmacokinetics of dapoxetine when taken concurrently.

Adverse effects:

• The most common effects on taking dapoxetine are nausea, dizziness, dry mouth, headache, diarrhea, and insomnia. Relapse due to adverse effects is related to dose. According to McMahon in a recent study in Asia, amputation rates of 0.3%, 1.7%, and 5.3% of 1067 have been studied with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively. In contrast to other SSRIs used to treat depression, which have been associated with a higher incidence of sexual dysfunction, dapoxetine is associated with lower rates of sexual dysfunction. Taken as needed, dapoxetine has very mild adverse effects of decreased libido (<1%) and erectile dysfunction (<4%).

Pregnancy:

May or may not be harmful to an unborn fetus. Consult a doctor if you are planning to conceive during dapoxetine hydrochloride treatment.

Fertility:

There is no information related to sperm measures, pregnancy results or fetal / fetal development on fertility.

Containdications:

• Dapoxetine should not be used in men with moderate to severe liver impairment and in receiving CYP3A4 inhibitors such as ketoconazole, ritonavir, and telithromycin. Dapoxetine may also not be used in patients with heart failure, permanent pacemakers, or other significant ischemic heart disease. Caution is advised in men receiving thioridazine, monoamine oxidase inhibitors, SSRIs, serotonin-norepinephrine reuptake inhibitors, or tricyclic antidepressants. If a patient stops taking one of these medicines, they should wait for 14 days before taking dapoxetine. If a patient stops taking dapoxetine, they should wait 7 days before receiving these drugs.

Breastfeeding:

It is not known whether dapoxetine or its metabolites are excreted in human milk.