Edsave Plus

Uses

Indicated for the treatment of premature ejaculation (PE) in men 18 to 64 years of age, who have all of the following:

• Persistent or recurrent ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the patient wishes.
• Marked personal distress or interpersonal difficulty as a consequence of PE and poor control over ejaculation.

Tadalafil is used for the treatment of erectile dysfunction (ED).

Tadalafil is used for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).

Tadalafil is used for the treatment of erectile dysfunction and the signs of benign prostatic hyperplasia (ED/BPH).

Edsave Plus is also used to associated treatment for these conditions: Premature EjaculationBenign Prostatic Hyperplasia (BPH), Erectile Dysfunction, Symptomatic pulmonary arterial hypertension (PAH)

How Edsave Plus works

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.

Penile erection during sexual stimulation is achieved by the relaxation of penile arteries and corpus cavernosal smooth muscles, leading to increased blood flow to the organ. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum, and is degraded by the cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum located around the penis. Tadalafil inhibits PDE5 and thereby enhances erectile function by increasing the amount of cGMP available.

Dosage

Edsave Plus dosage

Adult (18 to 64 years of age): The recommended starting dose for all patients is 30 mg, taken as needed approximately 1 to 3 hours prior to sexual activity. 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. The maximum recommended dosing frequency is one dose every 24 hours.

Erectile Dysfunction-

For Use as Needed:

• The recommended starting dose of Tadalafil for use as needed in most patients is 10 mg, taken prior to anticipated sexual activity.
• The dose may be increased to 20 mg or decreased to 5 mg, based on individual efficacy and tolerability. The maximum recommended dosing frequency is once per day in most patients.

For Once Daily Use:

• The recommended starting dose of Tadalafil for once daily use is 2.5 mg, taken at approximately the same time every day, without regard to timing of sexual activity.
• The Tadalafil dose for once daily use may be increased to 5 mg, based on individual efficacy and tolerability.

Patients with BPH or with ED and BPH-

• Intimate for once daily use for BPH: The recommended dose of Intimate for once daily use is 5 mg, taken at approximately the same time every day.
• Intimate for once daily use for ED+BPH: The recommended dose of Intimate for once daily use is 5 mg, taken at approximately the same time every day, without regard to timing of sexual activity.

Tadalafil may be taken without regard to food.

Side Effects

Dizziness, Headache, Somnolence, Tremor, Blurred vision, Tinnitus, Sinus congestion, Nausea, Diarrhea, Abdominal pain, Dry mouth, Fatigue, Insomnia, Hypertension.

Body as a whole: hypersensitivity reactions including rash, urticaria, facial edema, Stevens-Johnson syndrome, and exfoliative dermatitis.

Cardiovascular and cerebrovascular: Serious cardiovascular events, including myocardial infarction, sudden cardiac death, unstable angina pectoris, ventricular arrhythmia, stroke, transient ischemic attacks, chest pain, palpitations, and tachycardia, may occur. Most of the patients in whom these events have been reported had pre-existing cardiovascular risk factors. Hypotension (more commonly reported when tadalafil is given to patients who are already taking antihypertensive agents), hypertension, and syncope.

Skin and subcutaneous tissues: hyperhidrosis (sweating).

Gastrointestinal: abdominal pain and gastroesophageal reflux.

Nervous system: migraine, transient global amnesia.Respiratory system: epistaxis (nose bleed).

Special senses: blurred vision, nonarteritic anterior ischemic optic neuropathy, retinal vein occlusion, visual field defect.

Otologic: cases of sudden decrease or loss of hearing have been reported.

Toxicity

Oral, Rat LD₅₀ = 2000 mg/kg, no deaths or toxicity.

Precaution

Patient with bleeding disorders, epilepsy, susceptibility to angle-closure glaucoma or raised intraocular pressure. Not intended for use in women. Known CYP2D6 poor metabolisers.

Cardiovascular: Physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Potential for Drug Interactions When Taking Tadalafil for Once Daily Use Physicians should be aware that Tadalafil for once daily use provides continuous plasma Tadalafil levels and should consider this when evaluating the potential for interactions with medications (e.g., nitrates, alpha-blockers, anti-hypertensives and potent inhibitors of CYP3A4).

Prolonged Erection: There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention. Tadalafil should be used with caution in patients who have conditions that might predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia), or in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease).

Eye & Sudden Hearing Loss: Physicians should advise patients to stop use of all PDE5 inhibitors, including Tadalafil, and seek medical attention in the event of a sudden loss of vision in one or both eyes & sudden decrease or loss of hearing.

Alpha blockers and Antihypertensives: Physicians should discuss with patients the potential for Tadalafil to augment the blood-pressure-lowering effect of alpha blockers and antihypertensive medications. Caution is advised when PDE5 inhibitors are coadministered with alpha blockers Renal Insufficiency, Hepatic Impairment, Consumption of alcohol.

Interaction

CNS active medicinal products: The use of Dapoxetine in combination with CNS active medicinal products has not been systematically evaluated in patients with premature ejaculation. Consequently, caution is advised if the concomitant administration of Dapoxetine and such medicinal products is required.

PDE5 inhibitors: Tadalafil did not affect the pharmacokinetics of Dapoxetine. Sildenafil caused slight changes in Dapoxetine pharmacokinetics, which are not expected to be clinically significant. However, Dapoxetine should be prescribed with caution in patients who use PDE5 inhibitors due to possible reduced orthostatic tolerance.

Tamsulosin: Concomitant administration of single or multiple doses of 30 mg or 60 mg Dapoxetine to patients receiving daily doses of Tamsulosin did not result in changes in the pharmacokinetics of Tamsulosin. However, Dapoxetine should be prescribed with caution in patients who use alpha adrenergic receptor antagonists due to possible reduced orthostatic tolerance.

Warfarin: There are no data evaluating the effect of chronic use of Warfarin with Dapoxetine; therefore, caution is advised when Dapoxetine is used in patients taking Warfarin chronically.

Ethanol: Concomitant use of alcohol and Dapoxetine could increase the chance or severity of adverse reactions such as dizziness, drowsiness, slow reflexes, or altered judgment. Combining alcohol with Dapoxetine may increase these alcohol-related 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.

Volume of Distribution

• 63 L

Elimination Route

Rapidly absorbed.

After single oral-dose administration, the maximum observed plasma concentration (Cmax) of tadalafil is achieved between 30 minutes and 6 hours (median time of 2 hours). Absolute bioavailability of tadalafil following oral dosing has not been determined.

Half Life

Initial half-life of 1-2 hours.

17.5 hours

Clearance

• oral cl=2.5 L/hr

Elimination Route

Tadalafil is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).

Pregnancy & Breastfeeding use

Dapoxetine is not indicated for use by women. It is not known either dapoxetine or its metabolites are excreted through human breast milk.

It is not indicated for use in newborn, children or women.

Contraindication

• Patients with known hypersensitivity to Dapoxetine Hydrochloride.
• Patients with significant pathological cardiac conditions such as heart failure (NYHA class II-IV), conduction abnormalities (second or third degree AV block or sick sinus syndrome) not treated with a permanent pacemaker, significant ischemic heart disease of significant valvular disease.
• Concomitant treatment with monoamine oxidase inhibitors (MAOIs), thioridazine. Similarly, MAOIs or thioridazine should not be administered within 7 days after Dapoxetine has been discontinued.
• Concomitant treatment with serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) or other medicinal/herbal products with serotonergic effects or within 14 days of discontinuing treatment with these medicinal/herbal products.

Nitrates: Administration of tadalafil to patients who are using any form of organic nitrate, either regularly and/or intermittently, is contraindicated. In clinical pharmacology studies, tadalafil was shown to potentiate the hypotensive effect of nitrates.

Hypersensitivity Reactions: Tadalafil is contraindicated in patients with a known serious hypersensitivity to tadalafil. Hypersensitivity reactions have been reported, including Stevens-Johnson syndrome and exfoliative dermatitis.

Special Warning

Renal Insufficiency-

For Use as Needed:

• Mild (creatinine clearance 51 to 80 mL/min): No dose adjustment is required.
• Moderate (creatinine clearance 31 to 50 mL/min): A starting dose of 5 mg not more than once per day is recommended, and the,maximum dose should be limited to 10 mg not more than once in every 48 hours.
• Severe (creatinine clearance <30 mL/min and on hemodialysis): The maximum recommended dose is 5 mg not more than once in every 72 hours.

For Once Daily Use:

• Mild (creatinine clearance 51 to 80 mL/min): No dose adjustment is required. Moderate (creatinine clearance 31 to 50 mL/min): No dose adjustment is required.
• Severe (creatinine clearance <30 mL/min and on hemodialysis): Tadalafil for once daily use is not recommended.

Hepatic Impairment-

For Use as Needed:

• Mild or moderate: The dose should not exceed 10 mg once per day.
• Severe: Not recommended

For Once Daily Use:

• Mild or moderate: Tadalafil for once daily use has not been extensively evaluated in patients with hepatic insufficiency. Therefore, caution is advised if Tadalafil for once daily use is prescribed to these patients.
• Severe: Not recommended.

Geriatrics:

No dose adjustment is required in patients >65 years of age

Acute Overdose

There were no unexpected adverse events in a clinical pharmacology study of Dapoxetine with daily doses up to 240 mg. In general, symptoms of overdose with SSRIs include serotonin-mediated adverse reactions such as somnolence, gastrointestinal disturbances such as nausea and vomiting, tachycardia, tremor, agitation and dizziness. In cases of overdose, standard supportive measures should be adopted as required.

Adverse events were similar to those seen at lower doses. In case of overdose, standard supportive measure should be adopted as required

Storage Condition

Store below 30°C. Protect from light and moisture. Keep out of reach of children

Store below 30° C. Protect from light and moisture. Keep out of reach of children.

Innovators Monograph

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