VIAGRA® (sildenafil citrate) Tablets DESCRIPTION VIAGRA°, an oral therapy for erectile dysfunction, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Sildenafil citrate is designated chemically as 1-[(3-(6,7-dihydro-1-methy1-7-oxo-3-propy1-1H- pyrazolo[4,3-d]pyrimidin-5-y1)-4-ethoxyphenylisulfony1J-4-methylpiperazine citrate and has the following structural formula: Sildenafil citrate is a white to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7. VIAGRA (sildenafil citrate) is formulated as blue, film-coated rounded-diamond-shaped tablets equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration. In addition to the active ingredient, sildenafil citrate, each tablet contains the following inactive ingredients: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, lactose, triacetin. and FD & C Blue #2 aluminum lake. CLINICAL PHARMACOLOGY Mechanism of Action The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavemosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavemosum and allowing inflow of blood. Sildenafil has no direct relaxant effect on isolated human corpus cavemosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDES), which is responsible for degradation of cGMP in the corpus cavemosum. When sexual stimulation causes local release of NO, inhibition of PDES by sildenafil causes increased levels of cGMP in the corpus cavemosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavemosum. Sildenafil at recommended doses has no eff