Remember that no medicine is for everyone. If you use nitrate drugs, often used to control chest pain (also known as angina), don't take Sildenafil Citrate (The active ingredient in Viagra brand and Generic Viagra). This combination could cause your blood pressure to drop to an unsafe or life-threatening level. Be sure to ask your doctor if your heart is healthy enough for sexual activity.

For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity. However, sildenafil citrate (generic Viagra) may be taken anywhere from 4 hours to 0.5 hour before sexual activity. Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg. The maximum recommended dosing frequency is once per day.

The Following Factors are Associated with Increased Plasma Levels of Sildenafil: Age >65 (40% increase in AUC), hepatic impairment (e.g., cirrhosis, 80%), severe renal impairment (creatinine clearance <30 ml/min, 100%), and concomitant use of potent cytochrome P450 3A4 inhibitors (erythromycin, ketoconazole, itraconazole, 200%, saquinavir 210%). Since higher plasma levels may increase both the efficacy and incidence of adverse events, a starting dose of 25 mg should be considered in these patients.

Given the extent of the interaction with patients receiving concomitant therapy with ritonavir, it is recommended not to exceed a maximum single dose of 25 mg of sildenafil citrate in a 48 hour period.

Recommended Storage: Store at controlled room temperature, 15-30°C (59-86°F).

Mechanism of Action
The physiologic mechanism of genital erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum 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 cavernosum and allowing inflow of blood. Sildenafil citrate has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Caverta (generic Viagra) at recommended doses has no effect in the absence of sexual stimulation.

Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (>80-fold for PDE1, >1000-fold for PDE2, PDE3, and PDE4). The approximately 4000-fold selectivity for PDE5 versus PDE3 is important because that PDE is involved in control of cardiac contractility. Sildenafil citrate is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina; this lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels.
In addition to human corpus cavernosum smooth muscle, PDE5 is also found in lower concentrations in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle. The inhibition of PDE5 in these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo.

Consistent with its known effects on the nitric oxide/cGMP pathway, sildenafil citrate was shown to potentiate the hypotenive effects of nitrates and its administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is therefore contraindicated.

After patients have taken sildenafil, it is unknown when nitrates, if necessary, can be safely administered. Based on the parmacokinetic profile o a single 100 mg oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2ng/ml (compared to peak plasma levels of approximately 440ng/ml, in the following patients: age >65, hepatic impairment (e.g, creatinine clearance <30mL/min), and concomitant use of potent cytochrome P450 3A4 inhibitors (erythromycin), plasma levels of sildenafil at 24 hours post dose have been found to be 3 to 8 times higher than those seen in healthy volunteers. Although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely coadministered at this time point. Sildenafil is contraindicated in patients with a known hypersensitivity to any component o the tablet.