D-LAST 60

Indications

• Premature ejaculation

Dosage

Children: Not established; refer to BNF for Children for any applicable guidance.

Adults: Refer to BNF for specific dosing recommendations.

Mechanism of action

Dapoxetine works by inhibiting the reuptake of serotonin (5-HT) in the neuronal synapses, thereby enhancing serotonin activity. This mechanism influences the central ejaculatory neural circuit, which includes spinal and cerebral areas that coordinate ejaculation. Serotonin plays an inhibitory role in ejaculation, and dapoxetine's action on specific serotonin receptor subtypes (5-HT(1A), 5-HT(1B), and 5-HT(2C)) modulates this response effectively.

Pharmacodynamics

As a short-acting SSRI, dapoxetine uniquely reaches maximum serum concentration within about one hour and is rapidly eliminated from the body, with a half-life of 1-2 hours. This pharmacokinetic profile is advantageous for its use in treating premature ejaculation, as it allows for quick action without the prolonged side effects commonly associated with long-term SSRI use.

Pharmacokinetics

Dapoxetine is absorbed quickly after oral administration, with peak plasma concentrations occurring approximately one hour post-dose. It undergoes hepatic metabolism primarily via cytochrome P450 enzymes, and its elimination is predominantly renal. The short half-life allows for flexibility in dosing, as it can be taken on an as-needed basis prior to sexual activity.

Adverse effects

• nausea
• headache
• upset stomach
• weakness
• dermatological reactions
• lower sex drive
• increase in body weight

Interactions

• antifungals, azoles: Unknown (increases exposure)
• bupropion: Unknown (increases exposure)
• cinacalcet: Unknown (increases exposure)
• cobicistat: Unknown (increases exposure)
• crizotinib: Unknown (increases exposure)
• idelalisib: Unknown (increases exposure)
• imatinib: Unknown (increases exposure)
• letermovir: Unknown (increases exposure)
• nilotinib: Unknown (increases exposure)

Pregnancy

Dapoxetine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Safety in pregnancy has not been established.

Breast-feeding

It is unknown whether dapoxetine is excreted in human milk. Caution should be exercised when administering dapoxetine to nursing mothers.

Storage

Store below 30°C. Keep in a dry place and protect from light.

Formulations

• Tablets

Mechanism of action

The drug's mechanism of action is thought to be related to inhibition of neuronal reuptake of serotonin and subsequent potentiation of serotonin activity. The central ejaculatory neural circuit comprises spinal and cerebral areas that form a highly interconnected network. The sympathetic, parasympathetic, and somatic spinal centers, under the influence of sensory genital and cerebral stimuli integrated and processed at the spinal cord level, act in synergy to command physiologic events occurring during ejaculation. Experimental evidence indicates that serotonin (5-HT), throughout brain descending pathways, exerts an inhibitory role on ejaculation. To date, three 5-HT receptor subtypes (5-HT(1A), 5-HT(1B), and 5-HT(2C)) have been postulated to mediate 5-HT's modulating activity on ejaculation.

Pharmacodynamics

Dapoxetine is a selective serotonin reuptake inhibitor currently undergoing trials through Alza (under license from GenuPro, a collaboration between Eli Lilly and PPD). Dapoxetine is a short-acting SSRI drug currently being considered for approval by the Food and Drug Administration (FDA) for the treatment of premature ejaculation in men, which would make it the first drug approved for such treatment. Despite two clinical trials finished in 2006, experts doubt it will be approved by the FDA soon because SSRIs come with undesirable side-effects after long-term use, such as psychiatric problems, dermatological reactions, increase in body weight, lower sex-drive, nausea, headache, upset stomach and weakness, thus not significantly outweighing the benefit of premature ejaculation medication versus the risks. By contrast with SSRIs approved for depression, which take 2 weeks or longer to reach steady-state concentration, dapoxetine has a unique pharmacokinetic profile, with a short time to maximum serum concentration (about 1 h) and rapid elimination (initial half-life of 1-2 h).