SEAGRA TAB (Seldinafil)

SEAGRA
Sildenafil

Composition:
SEAGRA 50mg Tablets
Each film-coated tablet contains:
Sildenafil Citrate Eq to
Sildenafil
...... 50mg
(USP Specifications.)
SEAGRA 100mg Tablets
Each film-coated tablet contains:
Sildenafil Citrate, Eq, to
.... 100mg.
(USP Specifications.)

SEAGRA is an oral therapy for erectile dysfunction, which restores impaired erectile function by increasing blood flow to the penis, resulting in a natural response to sexual stimulation. The physiological mechanism responsible for the erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme, guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (CGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Sildenafil is a potent and selective inhibitor of GMP-specific phosphodiesterase type 5 (PDE5), which is responsible for the degradation of GMP in the corpus cavernosum. SEAGRA has a peripheral site of action on erections. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosal levels of cMP. Therefore, sexual stimulation is required for SEAGRA to produce its beneficial pharmacological effects.
Pharmacokinetic properties:
Absorption::
Sildenafil is rapidly absorbed. Maximum plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral bioavailability is 41% (range 25-63%). The oral pharmacokinetics of sildenafil are proportional over the récommended dose range (25-100 mg). When sildenafil is taken with a high-fat meal, the rate of absorption is reduced with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 29%. Patients may need to individualize their dosing relative to their food intake based on their own experienced clinical response.
Distribution:
The mean steady state volume of distribution (Vss) for sildenafil is 105 L, indicating distribution into the tissues. Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations.
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Biotransformation:
Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-demethylation of sildenafil. This metabolite has a PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% of the parent drug. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil. The N-desmethyl metabolite is further metabolised, with a terminal half-life of approximately 4 hours.
Elimination:
The total body clearance of sildenafil is 41 L/h with a resultant terminal phase half-life of 3-5 hours. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately-80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose).
Therapeutic indications:
SEAGRA is indicated for the treatment of erectile dysfunction in adult males.
Dose:
Use in Adults:
The recommended starting dose is 50 mg taken approximately one hour before sexual activity. Based on efficacy and toleration, the dose may be increased to 100 mg or decreased to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended dosing frequency is once per day.

 Dose Adjustments:
Dosage Adjustment in the Elderly:
Since sildenafil clearance is reduced in elderly patients, a first dose of 25 mg should be considered. Based on efficacy and toleration, the dose may be incréased to 50 mg and 100 mg.
Dosage Adjustment in Renal Impairment:
The dosing recommendations for Use in Adults should be followed for patients with mild to moderate renal impairment (Clcr = 30-80
mL/min). Since sildenafil clearance is reduced in patients with severe renal impairment (Cr <30ml/min), a 25 mg starting dose should be considered. Based on efficacy and toleration, the dose may be increased to 50 mg and 100 mg. Dosage Adjustment in Hepatic Impairment:
Since sildenafil clearance is reduced in patients with hepatic impairment (e.g, cirrhosis), a 25 mg starting dose should be considered. Based on efficacy and toleration, the dose may be increased to 50 mg and 100 mg.
Paediatric population:
There is no relevant use of SEAGRA in the paediatric population.
Overdose:
Overdose information is limited. In studies with healthy volunteers, adverse effects from single doses of up to 800 mg were similar to those seen at lower doses, but the incidence rates and severities were increased. Survival is reported in a 42-year-old female following an overdose of 2,000 mg of sildenafil. In cases of overdose, standard supportive measures should be adopted as required. Sildenafil blood levels are not clinically useful. Monitor ECG and blood pressure in patients who are symptomatic. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma protein and not eliminated in the urine.