Managing Potential Side Effects and Patient Guidance

PE is defined according to the International Society for Sexual Medicine (ISSM) guidelines as ejaculation that always happens in fewer than 1 minute following vaginal penetrating from the initial sexual encounter (lifelong PE), or a decrease in IELT, less than 3 min (acquired PE) with inability to delay ejaculation on all or nearly all vaginal penetrations and negative personal consequences, such as distress, frustration, bother and/or avoidance of sexual intimacy [Citation2].

• Use of dapoxetine 5mg may require dose adjustment over time.
• Erectile function is unaffected directly by dapoxetine.
• If a dose is missed, take it as soon as remembered.
• Do not double doses to compensate for missed ones.
• Potential for abnormal bleeding exists; inform your doctor.
• Step-by-step adherence ensures safe and effective use.
• Medical consultation should occur before any change in regimen.

Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) define PE as a persistent or recurrent ejaculation that occurs within approximately 1 minute after vaginal penetration and before the individual wishes it.

• Severe impairment is contraindicated
• Moderate impairment requires caution
• Reduced metabolism in liver disease
• Increased risk of side effects
• Dose adjustment is mandatory
• Avoid use in cirrhosis
• Monitor liver enzyme levels
• Risk of hepatotoxicity
• Consult a hepatologist
• Adjust dose carefully
• Safety not established in severe cases
• Use only if benefits outweigh risks

The problem must present for at least 6 months and present on almost all (approximately 75–100%) or on all occasions of sexual attempts with clinically significant distress and cannot be explained by a nonsexual mental disorder or as a result of severe relationship distress and is not attributable to the effects of a substance/medication or other medical condition [Citation3,Citation4].

• Proper hydration can help reduce side effects like dizziness.
• Always inform your doctor about existing medical conditions.
• Dapoxetine is part of a treatment plan for premature ejaculation.
• Avoid fatty or heavy meals immediately before taking dapoxetine.
• Keep a diary of medication effects for discussion with your doctor.
• Combining dapoxetine with other depression medications can be risky.
• Do not stop medication without medical advice.

A recent comprehensive novel classification of PE was reported by Raveendran A.

Adverse effects

Fluoxetine and paroxetine (but not other SSRIs) are potent CYP2D6 inhibitors so are predicted to decrease the metabolism of codeine to morphine, possibly reducing its analgesic efficacy. With concomitant use monitor patients for a reduced response to codeine and consider using an alternative analgesic if this is observed. SSRIs can lower the seizure threshold; concurrent use with tramadol that also lowers the seizure threshold may have an additive effect on the risk of seizure. In addition, tramadol may increase the risk of serotonin syndrome (see Interactions with common anaesthetic agents). Concomitant administration of tramadol with fluoxetine and paroxetine may result in reduced analgesic efficacy due to CYP2D6 inhibition.

STORAGE & DOSAGE:

Serotonin released from platelets potentiates platelet aggregation. SSRIs can block platelets reuptake of serotonin from the bloodstream leading to serotonin depletion, impairment of haemostatic function and an increased risk of bleeding. There are reports of prolonged bleeding time and/or bleeding abnormalities (gastrointestinal bleeding, gynaecological haemorrhages, ecchymoses, cutaneous or mucous bleedings) in patients receiving SSRIs. This risk is further increased with concomitant use of other medications known to affect platelet function (see Interactions with other common medicines used in the perioperative period). Observational studies suggest a link between SSRIs and an increased risk of perioperative bleeding, with one study indicating SSRIs increase the odds of in-hospital mortality, bleeding and readmission at 30 days.

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However, patient factors rather than medication factors could not be excluded as the cause. Other studies have shown increased need for red blood cell transfusions in patients having coronary artery bypass or orthopaedic surgery. However, a case-control study did not demonstrate an increase in blood loss following hip and knee arthroplasty. Clinicians should be aware that SSRIs may contribute to perioperative bleeding, further research is needed to determine the significance of this. Abruptly stopping or interrupting treatment with SSRIs is not recommended. In this classification, the grading of the severity of reduction of IELT was reported as mild or grade 1 (IELT of 2 to 3 minutes), moderate or grade 2 (IELT of 1 to less than 2 minutes), severe or grade 3 (IELT less than 1 minute), and extreme or grade 4 (ejaculation occurring prior to vaginal penetration) [Citation5]. Premature ejaculation is a frequent male sexual dysfunction, although the real incidence is unclear, 24% to 30% of males may be affected [Citation6,Citation7]. Several drugs as tricyclic antidepressants (e.g.

clomipramine) and tramadol could be used for treatment of PE. Selective serotonin-reuptake-inhibitors (SSRIs), like escitalopram, fluoxetine, serteralin, paroxetine and dapoxetine are the most common medications used for management of PE [Citation8–10].

As SSRI, dapoxetine was the first licenced drug with FDA approval used for on-demand management of PE. Dapoxetin acts by neglecting the effect for the different G protein coupled and ligand gated channels for all 5-hydroxytryptamin (5-HT) receptor subtypes, it inhibits the 5-HT transporter and activate the 5-HT 2C receptor, an action which diminishes the operation of 5-HT 1A receptor, thus reattaining equilibrium between the actions of 5-HT 1A and 5-HT 2C receptors and this leads to increased 5-HT levels in the synaptic clefts which results in delayed ejaculation [Citation11].

Regulatory Documentation Provided

Common withdrawal symptoms include dizziness, numbness, tingling, nausea, vomiting, headache, sweating, anxiety and sleep disorders. In some cases, withdrawal symptoms can be severe and disabling. Withdrawal reactions usually occur within 3 days of stopping an SSRI, although a delay of up to 2 weeks may be noted with fluoxetine due to its long half-life. Paroxetine and fluvoxamine are associated with a higher risk of withdrawal reactions, possibly due to their short half-lives. The risk sildenafil and dapoxetine of withdrawal is increased if SSRIs are stopped suddenly after regular administration for more than 8 weeks.

Stability study of PLGA NPs

Hyponatraemia, possibly as a result of inappropriate secretion of antidiuretic hormone has been associated with SSRIs. Caution is required in patients at increased risk of hyponatraemia, such as elderly, or volume depleted/dehydrated patients or patients treated with diuretics. & Norman, E. Anaesthetic implications of psychoactive drugs. Continuing Education in Anaesthesia Critical Care & Pain.

Benign prostatic hyperplasia and lower urinary tract symptoms: evidence and approaches for best case management

Summary of Product Characteristics – Priligy® (dapoxetine) 30mg film-coated tablets. Accessed via 24/07/2019 [date of revision of the text March 2019] Summary of Product Characteristics – Seroxat ® (paroxetine) 10mg tablets. Accessed via 18/07/2019 [date of revision of the text February 2019] British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. Nitric oxide (NO) activates guanylate cyclase which increases the intracellular cGMP in the corpus cavernosum causing smooth muscle relaxation. PDE-5 inhibitors act through increasing nitric oxide which causes relaxation of the smooth muscles of corpus cavernosum and the vas deferens and seminal-vesicles, also they reduce anxiety from sexual performance which is commonly associated with PE [Citation12]. According to several researches, using SSRIs and PDE-5 inhibitors together enhances sexual pleasure and boosts IELT when compared with taking SSRIs alone.

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Highly statistically significant improvements were found in the mean IELT and dapoxetine 60 mg buy online satisfaction scores 1, 2, and 3 months post-treatment in all groups (P = <0.001). Post hoc analysis suggested this improvement was more pronounced in group C (P < 0.001). Both tadalafil and dapoxetine are effective in the treatment of patients with premature ejaculation, but the combination of both drugs gives better results. Premature ejaculation (PE) is a male sexual disorder characterized by a brief intra-vaginal ejaculatory latency time (IELT) and lack of ability to properly control ejaculation which has detrimental personal effects [Citation1]. There is no global definition for PE. PDE-5 may suppress the central sympathetic tone, which causes better erection and increased the time interval for ejaculation [Citation13].

Supplementary Information

London: The Royal Pharmaceutical Society of Great Britain. Truven Health Analytics, Greenwood Village, Colorado, USA. Summary of Product Characteristics – Naropin ® (ropivacaine) 10mg/ml solution for injection. Accessed via 20/07/2019 [date of revision of the text February 2018] The Professionals’ Pocket Handbook and Aide Memoire. Summary of Product Characteristics – ProveBlue ® (methylthioninium chloride) 5mg/ml solution for injection.

Depression and anxiety

Accessed via 20/07/2019 [date of revision of the text February 2018] Summary of Product Characteristics – Cipramil ® (citalopram) Tablets. Accessed via 18/07/2019 [date of revision of the text March 2019] Summary of Product Characteristics – Cipralex ® (escitalopram) 10mg film-coated tablets. Accessed via 18/07/2019 [date of revision of the text January 2018] Summary of Product Characteristics – Prozac ® (fluoxetine) 20mg hard capsules. Accessed via 18/07/2019 [date of revision of the dapoxetine over counter text March 2018] Summary of Product Characteristics – Faverin ® (fluvoxamine) 50mg film-coated tablets. Accessed via 18/07/2019 [date of revision of the text October 2018] Summary of Product Characteristics – Lustral ® (sertraline) 100mg film-coated tablets.

Role of the phytoestrogenic, pro-apoptotic and anti-oxidative properties of silymarin in inhibiting experimental benign prostatic hyperplasia in rats

Selective serotonin reuptake inhibitors: depressing perioperative outcomes? Serotonin Reuptake Inhibitors and Bleeding Risks in Major Orthopaedic Procedures. To compare the efficacy of tadalafil alone, dapoxetine alone, and tadalafil with dapoxetine as a combination therapy for the treatment of premature ejaculation. Eligible patients attended our andrology clinic with premature ejaculation were randomly allocated into three groups: group A (92 participants) received on-demand tadalafil, 5 mg; group B (91 participants) were given on-demand dapoxetine, 30 mg; and group C (89 participants) received on-demand combination of tadalafil, 5 mg, and dapoxetine, 30 mg. We assessed the changes in the intravaginal ejaculatory latency time (IELT) and the satisfaction scores 1, 2, and 3 months after treatment. This study aimed to compare the pharmacological effect assessed by IELT in men suffering from PE by using either dapoxetine alone, tadalafil alone, or their combination as a primary outcome and to evaluate the possible side effects of drug therapy as a secondary outcome. This was a prospective, randomized work of patients who attended our andrology clinic with PE from May 2021 to September 2022.