SUSTINEX 30 TABLETS

Indications

• Premature ejaculation

Dosage

Children: Dapoxetine is not indicated for use in children or adolescents under 18 years of age.

Adults: Dapoxetine is typically used on an as-needed basis, with a recommended dose of 30 mg taken 1 to 3 hours before sexual activity. If necessary, the dose may be increased to 60 mg. It should not be taken more than once in a 24-hour period.

Mechanism of action

Dapoxetine inhibits the neuronal reuptake of serotonin, increasing its availability in the synaptic cleft. This potentiation of serotonin activity is thought to modulate the ejaculatory response through various serotonin receptor subtypes, such as 5-HT(1A), 5-HT(1B), and 5-HT(2C), which are involved in the central neural pathways regulating ejaculation.

Pharmacodynamics

As a selective serotonin reuptake inhibitor, dapoxetine enhances serotonin neurotransmission, which has a significant inhibitory effect on the ejaculatory reflex. This action is particularly beneficial for men experiencing premature ejaculation, as it allows for better control over ejaculation timing. Dapoxetine is noted for its rapid onset of action, often beginning to take effect within days of starting treatment.

Pharmacokinetics

Dapoxetine exhibits a rapid absorption profile, with peak plasma concentrations reached within approximately 1 hour after oral administration. Its elimination half-life is relatively short, ranging from 1 to 2 hours, allowing for a quick return to baseline levels after dosing. This pharmacokinetic profile supports its use as a PRN (as needed) medication for premature ejaculation rather than a daily regimen.

Contra-indications

• Anatomical deformation of the penis (e.g. angulation, cavernosal fibrosis, Peyronie's disease)
• Severe cardiovascular disease
• Severe cerebrovascular disease
• Use with other agents for erectile dysfunction
• History of priapism

Adverse effects

• Common: Bruising
• Common: Flushing
• Uncommon: Dizziness
• Uncommon: Headache
• Uncommon: Palpitations
• Uncommon: Tachycardia
• Rare: Angina pectoris
• Rare: Myocardial infarction
• Rare: Penile fibrosis (following multiple injections)
• Rare: Penile nodules
• Rare: Sexual dysfunction

Interactions

• Antifungals (azoles) may increase exposure to dapoxetine
• Bupropion may increase exposure to dapoxetine
• Cinacalcet may increase exposure to dapoxetine
• Cobicistat may increase exposure to dapoxetine
• Crizotinib may increase exposure to dapoxetine
• Idelalisib may increase exposure to dapoxetine
• Imatinib may increase exposure to dapoxetine
• Letermovir may increase exposure to dapoxetine
• Nilotinib may increase exposure to dapoxetine

Precautions

• Concomitant treatment with anticoagulants should be approached with caution
• Monitor for signs of penile angulation, cavernosal fibrosis, or Peyronie's disease
• Careful examination of the penis is recommended, particularly for patients undergoing self-injection therapy

Pregnancy

Use only if clearly needed, as safety in pregnancy has not been established.

Breast-feeding

It is not known whether dapoxetine is excreted in human milk; caution is advised.

Storage

Store in a refrigerator (2–8°C).

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).