Mechanism of Action

Dapoxetine is a selective serotonin reuptake inhibitor (SSRI) specifically designed for the treatment of premature ejaculation (PE) in males. It works by inhibiting the serotonin transporter, enhancing the action of serotonin at the pre- and postsynaptic receptors. This modulation leads to delayed ejaculation, providing a longer time until ejaculation and improving control over it.

Indications

Dapoxetine is indicated for adult men aged 18 to 64 years who have a diagnosis of premature ejaculation. Symptoms should include persistent or recurrent ejaculation with minimal sexual stimulation, occurring before or shortly after penetration and before the patient wishes. It can be used when the condition results in marked personal distress or interpersonal difficulty.

Dosage and Administration

The recommended starting dose of dapoxetine is 30 mg, taken as needed approximately 1 to 3 hours before sexual activity. If tolerated but not effective enough, the dose can be increased to a maximum recommended dose of 60 mg. It should not be taken more than once every 24 hours. It is intended for oral administration with a full glass of water. Patients should be advised to take dapoxetine only when anticipating sexual activity.

Pharmacokinetics

Dapoxetine is rapidly absorbed, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. The drug has a short half-life of 1.5 hours, reducing the risk of accumulation. It is extensively metabolized in the liver and kidneys, and its main metabolites are excreted in urine. Due to its rapid clearance, dapoxetine shows a low incidence of withdrawal symptoms.

Contraindications

Dapoxetine is contraindicated in patients with a known hypersensitivity to the active substance or any of the excipients. It should not be used in individuals with significant cardiac disease such as heart failure, conduction abnormalities like complete heart block, or ischemic heart disease. Its use is also contraindicated with monoamine oxidase inhibitors (MAOIs) and thioridazine. Dapoxetine should not be used in patients with a history of syncope.

Precautions

Patients should be assessed for orthostatic hypotension prior to starting dapoxetine. Those with a history of dizziness or fainting should exercise caution. The medication is not recommended in individuals with severe liver impairment as the hepatic metabolism of dapoxetine is critical for its clearance. Men with underlying erectile dysfunction (ED) should adequately manage ED before initiating dapoxetine for premature ejaculation.

Drug Interactions

Concomitant use of dapoxetine with potent inhibitors of CYP3A4, such as ketoconazole and ritonavir, can lead to increased plasma concentrations of dapoxetine. Co-administration with tramadol, SSRIs, SNRIs, and other serotonergic agents can increase the risk of serotonin syndrome. Using dapoxetine alongside PDE5 inhibitors for ED may increase the likelihood of hypotensive episodes.

Adverse Effects

Common side effects include nausea, dizziness, headache, and diarrhea. Psychiatric symptoms, such as anxiety and insomnia, have been reported. There is a potential for syncope, especially when rising abruptly from a seated or lying position. Cardiovascular effects, such as palpitations and an increased heart rate, may occur but are generally transient.

Use in Renal Impairment

For patients with mild or moderate renal impairment, no dose adjustment is required. However, caution is advised due to limited clinical data in this population. The use of dapoxetine in patients with severe renal impairment has not been extensively studied, and its use should be approached cautiously, weighing potential risks and benefits.

Special Populations

Dapoxetine is not recommended for men over the age of 65 due to limited data on its safety and efficacy in this age group. It should not be used in pediatric populations, as its safety profile has not been established. In ba individuals who are poor metabolizers of CYP2D6, caution is essential as these patients may have higher plasma concentrations of the drug.

Storage Instructions

Dapoxetine should be stored in its original package to protect it from moisture and light. The medication should be kept at room temperature, away from excess heat and humidity, typically in a range of 15-30°C (59-86°F). It should be kept out of reach of children to prevent accidental ingestion.

Monitoring Parameters

The patient should be monitored for response to therapy and any adverse effects. Regular assessment of blood pressure, heart rate, and signs of orthostatic hypotension is recommended. Monitoring for symptoms of serotonin syndrome, especially if used in conjunction with other serotonergic medications, is crucial. Continuation of therapy should be reassessed periodically to ascertain ongoing need and efficacy.

Patient Counseling Points

Patients should be informed about the potential for dizziness and advised to avoid situations where injury could result from syncope or loss of consciousness. The importance of dosing adherence should be stressed, including the maximum frequency of dosing. Explain the necessity to avoid alcohol use due to increased risk of syncope and sedation. Educate the patient on recognizing serotonin syndrome symptoms if taking other serotonergic drugs.