Drug used in Premature Ejaculation (Dapoxetine)/treatment of premature ejaculation

Drug used in Premature Ejaculation

Indications

Premature ejaculation 

Doses & Administration:

Recommended Starting Dose: 30 mg, taken as needed

approximately 1-3 hrs prior to sexual activity.

Maximum Recommended Dosing Frequency: Once every 24 hrs. If the effect of 30 mg is insufficient and the side effects are acceptable, the dose may be increased

to the maximum recommended dose of 60 mg.

Elderly (>65 years): Safety and efficacy of Dapoxetine

have not been established in patients >65 years as

|limited data are available in this population.

Children and Adolescents: Dapoxetine should not be

used in individuals <18 years.

Patients with Renal Impairment: No dose adjustment

is required but caution is advised in patients with

mild or moderate renal impairment. Dapoxetine is not

recommended for use in the patients with severe renal impairment.

Patients with Hepatic Impairment: No dose adjustment is required in patients with mild hepatic impairment.

Dapoxetine is contraindicated in patients with moderate and severe hepatic impairment.

Before treatment is initiated, the physician should obtain

a careful medical history focusing on past orthostatic events and also perform an orthostatic test (blood pressure and pulse rate, supine and standing). If the

patient discloses a history suggestive of orthostatic reactions or an orthostatic test shows this kind of reaction, treatment with Dapoxetine should be avoided.

Contraindications

Known hypersensitivity to dapoxetine HCI or to any of the excipients.

Patients with significant pathological cardiac conditions

eg, heart failure (NYHA class II-IV), conduction abnormalities (2nd- or 3rd-degree AV block or sick sinus syndrome) not treated with a permanent pacemaker,significant ischemic heart disease or significant valvular disease].

Concomitant treatment with monoamine oxidasen ihibitors (MAOIS), or within 14 days of discontinuing treatment with a MAOI. Similarly, a MAOI should not be

administered within 7 days after Dapoxetine has been

discontinued.

Concomitant treatment with thioridazine, or within

|4 days of discontinuing treatment with thioridazine.

Similarly, thioridazine should not be administered within

days after Dapoxetine has been discontinued.

Concomitant treatment with serotonin re-uptake inhibitors [selective serotonin re-uptake inhibitors

SSRIS), serotonin-norepinephrine re-uptake inhibitors

SNRIS), tricyclic antidepressants (TCAS)] or other

medicinal/herbal products with serotonergic effects or

vithin 14 days of discontinuing treatment with these

nedicinal/herbal products. Similarly these medicinal/

nerbal products should not be administered within 7

days after Dapoxetine has been discontinued.

 Side effects

Syncope characterized as loss of consciousness has

been reported.The majority of cases occurred during the

first 3 hrs after dosing, after the 1st dose or associated with study-related procedures in the clinic setting (eg.blood draw and orthostatic maneuvers and blood

pressure measurements). Prodromal symptoms often preceded the syncope.

Orthostatic hypotension has been reported in clinical trials.

The most common adverse drug reactions (5%)

reported during clinical trials were headache, dizziness,

nausea, diarrhea, insomnia and fatigue. The most common events leading to discontinuation were nausea

and dizziness.

Precautions & warnings

General: Dapoxetine is only indicated in men with PE.

Safety has not been established and there are no data on the ejaculation-delaying effects in men without PE.

Use with Recreational Drugs: Patients should be advised

not to use Dapoxetine in combination with recreational drugs. Recreational drugs with serotonergic activity

eg, ketamine, methylenedioxymethamphetamine

(MDMA) and lysergic acid diethylamide (LSD) may lead to potentially serious reactions if combined with

Dapoxetine. These reactions include, but are not limited

to, arrhythmia, hyperthermia and serotonin syndrome.

Use of Dapoxetine with recreational drugs with sedative

properties eg, narcotics and benzodiazepines may

further increase somnolence and dizziness.

Ethanol: Combining alcohol with Dapoxetine may

increase alcohol-related neurocognitive effects and may also enhance neurocardiogenic adverse events eg,

syncope, thereby increasing the risk of accidental injury;

therefore, patients should be advised to avoid alcohol while taking Dapoxetine.

Possibly prodromal symptoms eg, nausea, dizziness/

lightheadedness and diaphoresis were reported more

frequently among patients treated with Dapoxetine

compared to placebo.

Orthostatic Hypotension: An orthostatic test should be performed before initiating therapy. In case of a history of documented or suspected orthostatic reaction,

treatment with Dapoxetine should be avoided.

Dapoxetine is not indicated for psychiatric disorders and should not be used in men with these disorders

eg, schizophrenia, or in those suffering with co-morbid depression, as worsening of symptoms associated with

depression cannot be excluded.

Withdrawal Effects: Abrupt discontinuation of ohronically administered SSRIS used to treat chronic depressive disorders has been reported to result in the following symptoms: Dysphoric mood, irritability,

agitation, dizziness, sensory disturbances (eg,paresthesias, electric shock sensations), anxiety,confusion, headache, lethargy, emotional lability,insomnia and hypomania.

 Therapeutic Class

SSRIS & related anti-depressant drugs 

Mode of Action

Dapoxetine selectively inhibits the reuptake of oerotonin. It has limited direct action at other nurotransmitter sites including muscarinic receptors.

Interaction

Potential serious reactions w/ MAOIS.

nhibits metabolism of thioridazine. Risk of

serotonergic-associated effects w/ serotonergic medicinal/herbal products (including L-tryptophan,triptans, tramadol, linezolid, SSRIS, SNRIS, lithium & St.

John's wort prep). CNS-active medicinal products.

Possible reduction of clearance w/ CYP2D6, CYP3A4 &lavin monooxygenase 1 inhibitors. Increased exposure

W/ potent (eg ketoconazole, itraconazole, ritonavir,saquinavir, telithromycin, nefazodone, nelfinavir &atazanavir) & moderate (eg erythromycin, clarithromycin

iluconazole, amprenavir, fosamprenavir, aprepitant,verapamil, diltiazem) CYP3A4 inhibitors; potent CYP2D6 inhibitors.

Possible reduced orthostatic tolerance w/ PDE-5 inhibitors &?-adrenergic receptor antagonists. Increases plasma conc of desipramine & other drugs metabolized

CYP2D6. Decreases AUCinf of midazolam. Warfarin(Chronic therapy). Alcohol.