Chemical formula: C₂₁H₂₃NO Molecular mass: 305.413 g/mol PubChem compound: 71353
Dapoxetine interacts in the following cases:
Dapoxetine should not be used in patients using PDE5 inhibitors due to possible reduced orthostatic tolerance. The pharmacokinetics of dapoxetine (60 mg) in combination with tadalafil (20 mg) and sildenafil (100 mg) were evaluated in a single dose crossover study. Tadalafil did not affect the pharmacokinetics of dapoxetine. Sildenafil caused slight changes in dapoxetine pharmacokinetics (22% increase in AUCinf and 4% increase in Cmax), which are not expected to be clinically significant.
Concomitant use of dapoxetine with PDE5 inhibitors may result in orthostatic hypotension. The efficacy and safety of dapoxetine in patients with both premature ejaculation and erectile dysfunction concomitantly treated with dapoxetine and PDE5 inhibitors have not been established.
Patients should be advised not to use dapoxetine in combination with alcohol.
Combining alcohol with dapoxetine may increase alcohol-related neurocognitive effects and may also enhance neurocardiogenic adverse events such as syncope, thereby increasing the risk of accidental injury; therefore, patients should be advised to avoid alcohol while taking dapoxetine.
Concomitant treatment with moderate CYP3A4 inhibitors (e.g. erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil, diltiazem) may also give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers. The maximum dose of dapoxetine should be 30 mg if dapoxetine is combined with any of these drugs.
These two measures apply to all patients unless the patient has been verified to be a CYP2D6 extensive metabolizer by geno- or phenotyping. In patients verified to be CYP2D6 extensive metabolizers, a maximum dose of 30 mg is advised if dapoxetine is combined with a potent CYP3A4 inhibitor and caution is advised if dapoxetine in 60 mg doses is taken concomitantly with a moderate CYP3A4 inhibitor.
The Cmax and AUCinf of dapoxetine (60 mg single dose) increased by 50% and 88%, respectively, in the presence of fluoxetine (60 mg/day for 7 days). Considering the contribution of both unbound dapoxetine and desmethyldapoxetine, the Cmax of the active fraction may be increased by approximately 50% and the AUC of the active fraction may be doubled if taken with potent CYP2D6 inhibitors. These increases in the Cmax and AUC of the active fraction are similar to those expected for CYP2D6 poor metabolizers and may result in a higher incidence and severity of dose dependent adverse events.
Caution is advised in patients with mild or moderate renal impairment. Dapoxetine is not recommended for use in patients with severe renal impairment.
Dapoxetine should be prescribed with caution in patients taking medicinal products with vasodilatation properties (such as alpha adrenergic receptor antagonists and nitrates) due to possible reduced orthostatic tolerance.
Priligy should be used with caution in patients with raised intraocular pressure or those at risk of angle closure glaucoma.
Due to the potential of SSRIs to lower the seizure threshold, dapoxetine should be discontinued in any patient who develops seizures and avoided in patients with unstable epilepsy. Patients with controlled epilepsy should be carefully monitored.
Dapoxetine is not indicated for use by women.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy.
Dapoxetine is not indicated for use by women.
It is not known if either dapoxetine or its metabolites are excreted in human milk.
Dapoxetine is not indicated for use by women.
Animal studies do not indicate direct or indirect harmful effects with respect to fertility.
Dapoxetine has minor or moderate influence on the ability to drive and use machines. Dizziness, disturbance in attention, syncope, blurred vision and somnolence have been reported in subjects receiving dapoxetine in clinical trials. Therefore, patients should be warned to avoid situations where injury could result, including driving or operating hazardous machinery.
Combining alcohol with dapoxetine may increase alcohol-related neurocognitive effects and may also enhance neurocardiogenic adverse events such as syncope, thereby increasing the risk of accidental injury; therefore, patients should be advised to avoid alcohol while taking dapoxetine.
Syncope and orthostatic hypotension have been reported in clinical trials.
The following adverse drug reactions were reported during Phase 3 clinical trials most commonly and were dose related: nausea (11.0% and 22.2% in 30 mg and 60 mg prn dapoxetine groups, respectively), dizziness (5.8% and 10.9%), headache (5.6% and 8.8%), diarrhoea (3.5% and 6.9%), insomnia (2.1% and 3.9%) and fatigue (2.0% and 4.1%). The most common adverse events leading to discontinuation were nausea (2.2% of dapoxetine-treated subjects) and dizziness (1.2% of dapoxetine-treated subjects).
The safety of dapoxetine was evaluated in 4224 subjects with premature ejaculation who participated in five double-blind, placebo-controlled clinical trials. Of the 4224 subjects, 1616 received dapoxetine 30 mg as needed and 2608 received 60 mg, either as needed or once daily.
The following table presents the adverse reactions that have been reported.
Frequency of Adverse Reactions (MedDRA):
| System Organ Class | Very common (>1/10) | Common (≥1/100 to <1/10) | Uncommon (≥1/1000 to <1/100) | Rare (≥1/10000 to <1/1000) |
|---|---|---|---|---|
| Psychiatric disorders | Anxiety, Agitation, Restlessness, Insomnia, Abnormal dreams, Libido decreased | Depression, Depressed mood, Euphoric mood, Mood altered, Nervousness, Indifference, Apathy, Confusional state, Disorientation, Thinking abnormal, Hypervigilance, Sleep disorder, Initial insomnia, Middle insomnia, Nightmare, Bruxism, Loss of libido, Anorgasmia | ||
| Nervous system disorders | Dizziness, Headache | Somnolence, Disturbance in attention, Tremor, Paraesthesia | Syncope, Syncope vasovagal, Dizziness postural, Akathisia, Dysgeusia, Hypersomnia, Lethargy, Sedation, Depressed level of consciousness | Dizziness exertional, Sudden onset of sleep |
| Eye disorders | Vision blurred | Mydriasis, Eye pain, Visual disturbance | ||
| Ear and labyrinth disorders | Tinnitus | Vertigo | ||
| Cardiac disorders | Sinus arrest, Sinus bradycardia, Tachycardia | |||
| Vascular disorders | Flushing | Hypotension, Systolic hypertension, Hot flush | ||
| Respiratory, thoracic and mediastinal disorders | Sinus congestion, Yawning | |||
| Gastrointestinal disorders | Nausea | Diarrhoea, Vomiting, Constipation, Abdominal pain, Abdominal pain upper, Dyspepsia, Flatulence, Stomach discomfort, Abdominal distension, Dry mouth | Abdominal discomfort, Epigastric discomfort | Defaecation urgency |
| Skin and subcutaneous tissue disorders | Hyperhidrosis | Pruritis, Cold sweat | ||
| Reproductive system and breast disorders | Erectile dysfunction | Ejaculation failure, Male orgasmic disorder, Paraesthesia of genital male | ||
| General disorders and administration site conditions | Fatigue, Irritability | Asthenia, Feeling hot, Feeling jittery, Feeling abnormal, Feeling drunk | ||
| Investigations | Blood pressure increased | Heart rate increased, Blood pressure diastolic increased, Blood pressure orthostatic increased |
Adverse drug reactions reported in the 9-month long-term open-label extension trial were consistent with those reported in the double-blind studies and no additional adverse drug reactions were reported.
Syncope characterized as loss of consciousness, with bradycardia or sinus arrest observed in patients wearing Holter monitors, has been reported in clinical trials and is considered medicinal product-related. The majority of cases occurred during the first 3 hours after dosing, after the first dose or associated with study-related procedures in the clinical setting (such as blood draw and orthostatic maneuvers and blood pressure measurements). Prodromal symptoms often preceded the syncope.
The occurrence of syncope and possibly prodromal symptoms appears dose dependent as demonstrated by higher incidence among patients treated with higher than recommended doses in Phase 3 clinical trials.
Orthostatic hypotension has been reported in clinical trials.The frequency of syncope characterized as loss of consciousness in the dapoxetine clinical development program varied depending on the population studied and ranged from 0.06% (30 mg) to 0.23% (60 mg) for subjects enrolled in the Phase 3 placebo-controlled clinical trials to 0.64% (all doses combined) for Phase 1 non-PE healthy volunteer studies.
Caution is advised if increasing the dose to 60 mg in patients taking potent CYP2D6 inhibitors or if increasing the dose to 60 mg in patients known to be of CYP2D6 poor metabolizer genotype.
Abrupt discontinuation of chronically administered SSRIs used to treat chronic depressive disorders has been reported to result in the following symptoms: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g. paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia and hypomania.
Results of a safety study showed a slightly higher incidence of withdrawal symptoms of mild or moderate insomnia and dizziness in subjects switched to placebo after 62 days of daily dosing.
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