Adult: 18-64 years In men who have poor control over ejaculation, history of the condition for over the past 6 months, marked personal distress or interpersonal difficulty due to the condition, intravaginal ejaculatory latency time of <2 minutes, and recurrent or persistent ejaculation with minimal sexual stimulation prior to, on, or shortly following penetration and before the patient wishes: Initially, 30 mg to be taken approx 1-3 hours before sexual activity as necessary. If response is inadequate and the initial dose is well-tolerated (no experience of moderate or severe adverse effects or symptoms suggesting syncope), may increase up to a single dose of 60 mg to be taken approx 1-3 hours before sexual activity as necessary. Max: 60 mg once 24 hourly. Dose must only be taken when sexual activity is anticipated, and it should not be taken more frequently than once every 24 hours. Not intended for continuous daily use. Review treatment after the 1st 4 weeks (or at least after 6 doses) and at least every 6 months thereafter.
Nhóm bệnh nhân đặc biệt
Patients taking potent CYP2D6 inhibitors: Use caution if increasing the dose to 60 mg.
Dapoxetine is mainly metabolised by multiple enzymes including CYP2D6, CYP3A4 and flavin monooxygenase (FMO1) into dapoxetine-N-oxide (major inactive metabolite), desmethyldapoxetine and didesmethyldapoxetine (active metabolites). Desmethyldapoxetine is the active metabolite with equipotent activity to dapoxetine. CYP2D6 polymorphism may affect the exposure of both dapoxetine and desmethyldapoxetine, and the safety of the drug.
CYP2D6 extensive metabolisers
Recommended Max dose of dapoxetine is 30 mg if taken concurrently with a potent CYP3A4 inhibitor. Use caution if 60 mg dapoxetine doses are taken with moderate CYP3A4 inhibitors.
CYP2D6 poor metabolisers
According to research, patients who lack functional CYP2D6 enzyme had approx 31% higher plasma concentrations and 36% higher exposure of dapoxetine, and 98% higher plasma levels and 161% higher exposure of desmethyldapoxetine as compared to CYP2D6 extensive metabolisers. The plasma concentration and exposure of the active fraction of dapoxetine may be increased by approx 46% and 90%, respectively, which may result in higher incidence and severity of dose-related adverse events. Therefore, caution must be exercised if increasing the dapoxetine dose to 60 mg. Concomitant use with potent CYP3A4 inhibitors is contraindicated.
Currently, there are no recommendations for CYP2D6 gene testing before initiating treatment with dapoxetine.
Suy thận
CrCl (mL/min)
Dosage
<30
Not recommended.
Suy gan
Moderate to severe (Child-Pugh class B and C): Contraindicated.
Cách dùng
May be taken with or without food. Swallow tab whole & take w/ a full glass of water.
Chống chỉ định
Significant cardiac disease such as NYHA class II-IV heart failure, conduction abnormalities (e.g. atrioventricular block, sick sinus syndrome), significant ischaemic or valvular heart disease, orthostatic hypotension, history of syncope; uncontrolled epilepsy, history of mania/hypomania, bipolar disorder, or severe depression. Moderate to severe hepatic impairment (Child-Pugh class B and C). Concomitant use with potent CYP3A4 inhibitors (except in patients confirmed to be CYP2D6 extensive metabolisers). Use with MAOIs, thioridazine, other SSRIs, TCAs, serotonin-norepinephrine reuptake inhibitors (SNRIs) and medicinal or herbal agents with serotonergic effects (concomitant use, within 7 days of stopping dapoxetine, or within 14 days of stopping MAOIs, thioridazine, SSRIs, TCAs, SNRIs or serotonergic medicinal or herbal agents).
Thận trọng
Patient with controlled epilepsy, history of bleeding or coagulation disorders; high intraocular pressure or at risk of angle-closure glaucoma. Not indicated for use in women, or for psychiatric disorders including depression. Not recommended in patients with severe renal impairment (CrCl <30 mL/min). Not for use in men with erectile dysfunction who are taking phosphodiesterase-5 (PDE5) inhibitors. CYP2D6 extensive and poor metabolisers. Patients taking potent CYP2D6 inhibitors or moderate CYP3A4 inhibitors. Mild hepatic impairment (Child-Pugh class A) and mild to moderate renal impairment (CrCl 30-80 mL/min).
Tác dụng không mong muốn
Significant: Impaired platelet aggregation leading to increased bleeding risk; orthostatic hypotension, bone fracture, ocular effects (e.g. mild pupillary dilation which may lead to episode of narrow-angle glaucoma, eye pain), syndrome of inappropriate antidiuretic hormone secretion (SIADH), seizure, CNS effects (e.g. dizziness, blurred vision, somnolence, loss of attention), mild withdrawal symptoms. Rarely, syncope, hyponatraemia. Ear and labyrinth disorders: Tinnitus. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, abdominal pain, distension or discomfort, flatulence, dyspepsia, dry mouth. General disorders and administration site conditions: Fatigue, irritability. Investigations: Increased blood pressure. Nervous system disorders: Headache, tremor, paraesthesia. Psychiatric disorders: Anxiety, agitation, insomnia, restlessness, abnormal dreams. Reproductive system and breast disorders: Erectile dysfunction, decreased libido. Respiratory, thoracic and mediastinal disorders: Yawning, sinus congestion. Skin and subcutaneous tissue disorders: Hyperhidrosis. Vascular disorders: Flushing. Potentially Fatal: Serotonin syndrome.
Thông tin tư vấn bệnh nhân
This drug may cause dizziness, somnolence, blurred vision or lightheadedness; if affected, do not drive or operate machinery. If prodromal symptoms (e.g. lightheadedness soon after standing) occur, immediately lie down so the head is lower than the rest of the body or sit down and place the head between the knees until symptoms pass. Avoid rising quickly after prolonged lying or sitting.
Chỉ số theo dõi
Perform orthostatic test (blood pressure and heart rate in supine and standing positions) before treatment initiation. Assess men with other forms of sexual dysfunction (including erectile dysfunction) or underlying signs and symptoms of depression (to rule out undiagnosed depressive disorders) before treatment. Closely monitor for signs or symptoms of serotonin syndrome, syncope, depression, mania; suicidal ideation (particularly at the start of treatment or during dose increase or decrease).
May significantly increase dapoxetine serum concentrations and exposure with potent CYP2D6 inhibitors (e.g. fluoxetine) and moderate CYP3A4 inhibitors (e.g. fluconazole, verapamil, amprenavir, aprepitant, clarithromycin). May increase the risk of bleeding abnormalities with agents known to affect platelet function (e.g. warfarin, aspirin, NSAIDs, antiplatelets, atypical antipsychotics). May result in reduced orthostatic tolerance with α-adrenergic receptor antagonists, nitrates or PDE5 inhibitors. Potentially Fatal: Increased serum concentration and exposure levels with potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, nefazodone, telithromycin). May increase the risk of serotonin syndrome with MAOIs, other SSRIs, SNRIs, TCAs, and other agents with serotonergic effects (e.g. tryptophan, triptans, tramadol, lithium). May inhibit the metabolism of thioridazine resulting in increased thioridazine levels which may cause QTc interval prolongation.
Tương tác với thức ăn
Concomitant use with alcohol may increase the incidence or severity of alcohol-related effects (e.g. dizziness, drowsiness) and may also enhance neurocardiogenic adverse events (e.g. syncope); avoid combination. May increase the risk of serotonin syndrome with St. John's wort; avoid concomitant use. Avoid grapefruit juice within 24 hours before administration, as it may elevate the serum levels of dapoxetine.
Tác dụng
Description: Mechanism of Action: Dapoxetine is a potent, short-acting SSRI. Its exact mechanism for ejaculatory pathway inhibition is presumed to be connected to the blocking of neuronal serotonin reuptake and the subsequent potentiation of the action of neurotransmitters at pre- and postsynaptic receptors. Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Absolute bioavailability: 42% (range: 15-76%). Time to peak plasma concentration: Approx 1-2 hours. Distribution: Volume of distribution: 162 L. Plasma protein binding: >99% (dapoxetine); 98.5% (desmethyldapoxetine). Metabolism: Extensively metabolised by several enzymes, primarily CYP2D6, CYP3A4 and flavin monooxygenase (FMO1) mainly via N-oxidation, N-demethylation, naphthyl hydroxylation, glucuronidation and sulfation into multiple metabolites such as dapoxetine-N-oxide (major inactive metabolite), desmethyldapoxetine and didesmethyldapoxetine (<3% active metabolites). Excretion: Via urine (as conjugates). Elimination half-life: Approx 1.5 hours (initial phase); approx 19 hours (terminal phase).
Đặc tính
Source: National Center for Biotechnology Information. PubChem Database. Dapoxetine, CID=71353, https://pubchem.ncbi.nlm.nih.gov/compound/Dapoxetine (accessed on Jan. 20, 2020)
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