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In a double-blind study, 144 patients with erectile dysfunction and chronic stable angina limited by exercise, not receiving chronic oral nitrates, were randomized to a single dose of placebo or sildenafil 100 mg 1 hour prior to exercise testing.

Ingredient Function Concentration Notes
Sildenafil Citrate Active pharmaceutical ingredient 25 mg or 50 mg Common doses in oral strips
Sweeteners Improve taste Variable Sucralose, aspartame
Flavorings Enhance flavor Natural/Artificial Mint, strawberry, citrus
Binders Maintain structure Hydroxypropyl methylcellulose Ensures strip integrity
Stabilizers Preserve shelf life Ascorbic acid Prevent degradation

The primary endpoint was time to limiting angina in the evaluable cohort. The mean times (adjusted for baseline) to onset of limiting angina were 423.6 and 403.7 seconds for sildenafil (N=70) and placebo, respectively.

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There were no severe adverse events potentially related to blood pressure and no episodes of syncope reported in this study. In the third study, a single oral dose of sildenafil 100 mg or matching placebo was administered in a 3-period crossover design to 20 generally healthy males with BPH. In dose period 1, subjects were administered open label doxazosin and a single dose of sildenafil 50 mg simultaneously, after sildenafil pricing at least 14 consecutive days of doxazosin. If a subject did not successfully complete this first dosing period, he was discontinued from the study. Subjects who had successfully completed the previous doxazosin interaction study (using sildenafil 50 mg), including no significant hemodynamic adverse events, were allowed to skip dose period 1.

5.7 Combination with other PDE5 Inhibitors or Other Erectile Dysfunction Therapies

Treatment with doxazosin continued for at least 7 days after dose period 1. Thereafter, sildenafil 100 mg or matching placebo was administered simultaneously with doxazosin 4 mg (14 subjects) or doxazosin 8 mg (6 subjects) in standard crossover fashion. The mean subject age in this study was 66.4 years. Two were discontinued after study period 1: one failed to meet pre-dose screening qualifications and the other experienced symptomatic hypotension as a moderately severe adverse event 30 minutes after dosing with open-label sildenafil 50 mg. Of the twenty subjects who were ultimately assigned to treatment, a total of 13 subjects successfully completed dose period 1, and seven had successfully completed the previous doxazosin study (using sildenafil 50 mg).

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For the 20 subjects who received sildenafil 100 mg and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 100 mg sildenafil citrate or matching placebo are shown in Figure 5. Figure5: Mean Standing Systolic Blood Pressure Change from Baseline Blood pressure was measured after administration of sildenafil at the same times as those specified for the previous doxazosin studies. There lovegra sildenafil were three subjects who had a standing SBP of <85 mmHg. All three were taking sildenafil 100 mg, and all three reported mild adverse events at the time of reductions in standing SBP, including vasodilation and lightheadedness. There were four subjects with a decrease from baseline in standing systolic BP >30 mmHg following sildenafil 100 mg, one subject with a decrease from baseline in standing systolic BP >30 mmHg following placebo and one subject with a decrease from baseline in standing systolic BP >30 mmHg following both sildenafil citrate and placebo. These results demonstrated that the effect of sildenafil on the primary endpoint was statistically non-inferior to placebo.

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Effects ofSildenafil on Vision:At single oral doses of 100 mg and 200 mg, transient dose-related impairment of color discrimination was detected using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels.

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This finding is sildenafil film tablet consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. Subjects in the study reported this finding as difficulties in discriminating blue/green. An evaluation of visual function at doses up to twice the maximum recommended dose revealed no effects of sildenafil on visual acuity, intraocular pressure, or pupillometry. Effects ofSildenafilon Sperm: There was no effect on sperm motility or morphology after single 100 mg oral doses of sildenafil in healthy volunteers.

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In one small, open-label, uncontrolled, pilot study, eight patients with stable ischemic heart disease underwent Swan-Ganz catheterization. A total dose of 40 mg sildenafil was administered by four intravenous infusions. The results from this pilot study are shown in Table 3; the mean resting systolic and diastolic blood pressures decreased by 7% and 10% compared to baseline in these patients. Mean resting values for right atrial pressure, pulmonary artery pressure, pulmonary artery occluded pressure and cardiac output decreased by 28%, 28%, 20% and 7% respectively. Even though this total dosage produced plasma sildenafil concentrations which were approximately 2 to 5 times higher than the mean maximum plasma concentrations following a single oral dose of 100 mg in healthy male volunteers, the hemodynamic response to exercise was preserved in these patients. Sildenafil is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (range 25-63%). The pharmacokinetics of sildenafil are dose-proportional over the recommended dose range.

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While there were no severe adverse events potentially related to blood pressure reported in this study, one subject reported moderate vasodilatation after both sildenafil 50 mg and 100 mg. There were no episodes of syncope reported in this study. Effect ofSildenafilon Blood Pressure When Co-administered with Antihypertensives:When sildenafil 100 mg oral was co-administered with amlodipine, 5 mg or 10 mg oral, to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic. Effect ofSildenafilon Blood Pressure When Co-administered with Alcohol:Sildenafil 50 mg did not potentiate the hypotensive effect of alcohol (0.5 g/kg) in healthy volunteers with mean maximum blood alcohol levels of 0.08%. The maximum observed decrease in systolic blood pressure was -18.5 mmHg when sildenafil was co-administered with alcohol versus -17.4 mmHg when alcohol was administered alone.

Rapid Acting

The maximum observed decrease in diastolic blood pressure was -17.2 mmHg when sildenafil was co-administered with alcohol versus -11.1 mmHg when alcohol was administered alone. There were no reports of postural dizziness or orthostatic hypotension. The maximum recommended dose of 100 mg sildenafil was not evaluated in this study [see Drug Interactions (7.5)]. Effects ofSildenafilon Cardiac Parameters:Single oral doses of sildenafil up to 100 mg produced no clinically relevant changes in the ECGs of normal male volunteers. Studies have produced relevant data on the effects of sildenafil citrate on cardiac output. It is eliminated predominantly by hepatic metabolism (mainly CYP3A4) and is converted to an active metabolite with properties similar to the parent, sildenafil.

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Both sildenafil and the metabolite have terminal half-lives of about 4 hours. Figure6: Mean Sildenafil Plasma Concentrations in Healthy Male Volunteers Absorption and Distribution:SILDENAFIL ORAL FILM is rapidly absorbed.

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Maximum observed plasma concentrations are reached within 30 to 300 minutes (median 80 minutes) of oral dosing in the fasted state. After a single dose of 100 mg of SILDENAFIL ORAL FILM in adult males, the mean (coefficient of variation, %) peak plasma concentration (Cmax) and area under the concentration curve (AUC) of sildenafil were 503.5 (37.7%) ng/mL and 1902.4 (36.3%) ng·h/mL, respectively.

12. Sildenafil Oral Film - Clinical Pharmacology

There were no reports of syncope among these patients. For these four subjects, the placebo-subtracted mean maximum decreases from baseline in supine and standing systolic blood pressures were 14.8 mmHg and 21.5 mmHg, respectively. Two of these subjects had a standing SBP <85mmHg. Both these subjects were protocol violators, one due to a low baseline standing SBP, and the other due to baseline orthostatic hypotension. In the second study, a single oral dose of sildenafil 50 mg or matching placebo was administered in a 2-period crossover design to 20 generally healthy males with BPH.

8.1 Pregnancy

Following at least 14 consecutive days of doxazosin, sildenafil 50 mg or matching placebo was administered simultaneously with doxazosin 4 mg (17 subjects) or with doxazosin 8 mg (3 subjects). The mean subject age in this study was 63.9 years. Twenty subjects received sildenafil 50 mg, but only 19 subjects received matching placebo. One patient discontinued the study prematurely due to an adverse event of hypotension following dosing with sildenafil 50 mg. This patient had been taking minoxidil, a potent vasodilator, during the study.

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For the 19 subjects who received both sildenafil and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 50 mg sildenafil or matching placebo are shown in Figure 4. Figure4: Mean Standing Systolic Blood Pressure Change from Baseline Blood pressure was measured after administration of sildenafil at the same times as those specified for the first doxazosin study. There were two subjects who had a standing SBP of <85 mmHg. In these two subjects, hypotension was reported as a moderately severe adverse event, beginning at approximately 1 hour after administration of sildenafil 50 mg and resolving after approximately 7.5 hours. There was one subject with a decrease from baseline in standing systolic BP >30mmHg following sildenafil 50 mg and one subject with a decrease from baseline in standing systolic BP >30 mmHg following both sildenafil 50 mg and placebo. When SILDENAFIL ORAL FILM is taken with a high fat meal, the rate of absorption is reduced, with a mean delay in Tmax of 87 minutes and a mean reduction in Cmax of 45%. In a clinical study in 35 healthy males (18-55 years old) where SILDENAFIL ORAL FILM 100 mg was administered in fed conditions with or without water, no clinically significant differences in pharmacokinetics of sildenafil and its major N-desmethyl metabolite was observed.