How Sildenafil 60mg Works in the Body

VIAGRA is formulated as blue, film-coated rounded-diamond-shaped tablets equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration.

What special precautions should I follow?

Two of these subjects had a standing SBP < 85mmHg. Both of 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 VIAGRA 50 mg or matching placebo was administered in a 2-period crossover design to 20 generally healthy males with BPH. Following at least 14 consecutive days of doxazosin, VIAGRA 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.

Platelet-aggregation Inhibitors

Twenty subjects received VIAGRA 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 VIAGRA 50 mg. This patient had been taking minoxidil, a potent vasodilator, during the study. For the 19 subjects who received both VIAGRA 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 VIAGRA or matching placebo are shown in Figure 3. Figure 3: Mean Standing Systolic Blood Pressure Change from Baseline Blood pressure was measured after administration of VIAGRA at the same times as those specified for the first doxazosin study. The physiologic mechanism of 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. 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. Sildenafil at recommended doses has no effect in the absence of sexual stimulation.

• Sildenafil 60mg is one of several doses available.
• Your doctor may adjust the dose based on response.
• Use only the dose prescribed to you.
• Do not self-adjust the medication without medical advice.

Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (10-fold for PDE6, >80-fold for PDE1, >700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). Sildenafil is approximately 4,000-fold more selective for PDE5 compared to PDE3.

PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision [see Clinical Pharmacology (12.2)]. In addition to human corpus cavernosum smooth muscle, PDE5 is also found in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testis, and seminal vesicle.

How should this medicine be used?

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 VIAGRA 50 mg and resolving after approximately 7.5 hours. There was one subject with a decrease from baseline in standing systolic BP >30mmHg following VIAGRA 50 mg and one subject with a decrease from baseline in standing systolic BP > 30 mmHg following both VIAGRA 50 mg and placebo. 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 VIAGRA 100 mg or matching placebo was administered in a 3-period crossover design to 20 generally healthy males with BPH.

Therapies for Erectile Dysfunction

In dose period 1, subjects were administered open-label doxazosin and a single dose of VIAGRA 50 mg simultaneously, after 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 VIAGRA 50 mg), including no significant hemodynamic adverse events, were allowed to skip dose period 1. Treatment with doxazosin continued for at least 7 days after dose period 1. The inhibition of PDE5 in some of these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of NO observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo. Effects of VIAGRA on Erectile Response: In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (RigiScan®), after VIAGRA administration compared with placebo. Most studies assessed the efficacy of VIAGRA approximately 60 minutes post dose. The erectile response, as assessed by RigiScan®, generally increased with increasing sildenafil dose and plasma concentration. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours. Effects of VIAGRA on Blood Pressure: Single oral doses of sildenafil (100 mg) administered to healthy volunteers produced decreases in sitting blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8.3/5.3 mmHg). The decrease in sitting blood pressure was most notable approximately 1–2 hours after dosing, and was not different than placebo at 8 hours. Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg of VIAGRA, therefore the effects are not related to dose or plasma levels within this dosage range. Larger effects were recorded among patients receiving concomitant nitrates [see Contraindications (4.1)]. Figure 1: Mean Change from Baseline in Sitting Systolic Blood Pressure, Healthy Volunteers. Effects of VIAGRA on Blood Pressure When Nitroglycerin is Subsequently Administered: Based on the pharmacokinetic profile of a single 100 mg oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2 ng/mL (compared to peak plasma levels of approximately 440 ng/mL). In the following patients: age >65 years, hepatic impairment (e.g., cirrhosis), severe renal impairment (e.g., creatinine clearance <30 mL/min), and concomitant use of erythromycin or strong CYP3A4 inhibitors, 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.

Usual Adult Dose for Pulmonary Hypertension

This lower selectivity is thought to be the basis for abnormalities related to color vision [see Clinical Pharmacology (12.2)]. In addition to human corpus cavernosum smooth muscle, PDE5 is also found in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testis, and seminal vesicle. The inhibition of PDE5 in some of these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of NO observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo. Effects of VIAGRA on Erectile Response: In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (RigiScan®), after VIAGRA administration compared with placebo. Most studies assessed the efficacy of VIAGRA approximately 60 minutes post dose.

Dosage adjustments

The erectile response, as assessed by RigiScan®, generally increased with increasing sildenafil dose and plasma concentration. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours. Effects of VIAGRA on Blood Pressure: Single oral doses of sildenafil (100 mg) administered to healthy volunteers produced decreases in sitting blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8.3/5.3 mmHg). The decrease in sitting blood pressure was most notable approximately 1–2 hours after dosing, and was not different than placebo at 8 hours. Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg of VIAGRA, therefore the effects are not related to dose or plasma levels within this dosage range. 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 co-administered at this time point [see Contraindications (4.1)]. Effects of VIAGRA on Blood Pressure When Co-administered with Alpha-Blockers: Three double-blind, placebo-controlled, randomized, two-way crossover studies were conducted to assess the interaction of VIAGRA with doxazosin, an alpha-adrenergic blocking agent. In the first study, a single oral dose of VIAGRA 100 mg or matching placebo was administered in a 2-period crossover design to 4 generally healthy males with benign prostatic hyperplasia (BPH). Following at least 14 consecutive daily doses of doxazosin, VIAGRA 100 mg or matching placebo was administered simultaneously sildenafil citrate 150 mg red pill with doxazosin. Following a review of the data from these first 4 subjects (details provided below), the VIAGRA dose was reduced to 25 mg. Thereafter, 17 subjects were treated with VIAGRA 25 mg or matching placebo in combination with doxazosin 4 mg (15 subjects) or doxazosin 8 mg (2 subjects). The mean subject age was 66.5 years.

Further information

The mean subject age was 66.5 years. For the 17 subjects who received VIAGRA 25 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 25 mg VIAGRA or matching placebo are shown in Figure 2. Figure 2: Mean Standing Systolic Blood Pressure Change from Baseline Blood pressure was measured immediately pre-dose and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours after VIAGRA or matching placebo. Outliers were defined as subjects with a standing systolic blood pressure of <85 mmHg or a decrease from baseline in standing systolic blood pressure of >30 mmHg at one or more timepoints. There were no subjects treated with VIAGRA 25 mg who had a standing SBP < 85mmHg.

Key takeaways

There were three subjects with a decrease from baseline in standing systolic BP >30mmHg following VIAGRA 25 mg, one subject with a decrease from baseline in standing systolic BP > 30 mmHg following placebo and two subjects with a decrease from baseline in standing systolic BP > 30 mmHg following both VIAGRA and placebo. No severe adverse events potentially related to blood pressure effects were reported in this group. Of the four subjects who received VIAGRA 100 mg in the first part of this study, a severe adverse event related to blood pressure effect was reported in one patient (postural hypotension that began 35 minutes after dosing with VIAGRA with symptoms lasting for 8 hours), and mild adverse events potentially related to blood pressure effects were reported in two others (dizziness, headache and fatigue at 1 hour after dosing; and dizziness, lightheadedness and nausea at 4 hours after dosing). 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. For the 17 subjects who received VIAGRA 25 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 25 mg VIAGRA or matching placebo are shown in Figure 2. Figure 2: Mean Standing Systolic Blood Pressure Change from Baseline Blood pressure was measured immediately pre-dose and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours after VIAGRA or matching placebo. Outliers were defined as subjects with a standing systolic blood pressure of <85 mmHg or a decrease from baseline in standing systolic blood pressure of >30 mmHg at one or more timepoints. There were no subjects treated with VIAGRA 25 mg who had a standing SBP < 85mmHg.

There were three subjects with a decrease from baseline in standing systolic BP >30mmHg following VIAGRA 25 mg, one subject with a decrease from baseline in standing systolic BP > 30 mmHg following placebo and two subjects with a decrease from baseline in standing systolic BP > 30 mmHg following both VIAGRA and placebo. No severe adverse events potentially related to blood pressure effects were reported in this group.

Uses for Revatio

VIAGRA is formulated as blue, film-coated rounded-diamond-shaped tablets equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration. The physiologic mechanism of 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. 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. Sildenafil at recommended doses has no effect in the absence of sexual stimulation.

More common

Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (10-fold for PDE6, >80-fold for PDE1, >700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). Sildenafil is approximately 4,000-fold more selective for PDE5 compared to PDE3. PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is involved in the phototransduction pathway of the retina. Of the four subjects who received VIAGRA 100 mg in the first part of this study, a severe adverse event related to blood pressure effect was reported in one patient (postural hypotension that began 35 minutes after dosing with VIAGRA with symptoms lasting for 8 hours), and mild adverse events potentially related to blood pressure effects were reported in two others (dizziness, headache and fatigue at 1 hour after dosing; and dizziness, lightheadedness and nausea at 4 hours after dosing). 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 of 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 VIAGRA 50 mg or matching placebo was administered in a 2-period crossover design to 20 generally healthy males with BPH.

Following at least 14 consecutive days of doxazosin, VIAGRA 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 VIAGRA 50 mg, but only 19 subjects received matching placebo.

Reviews for Sildenafil

Larger effects were recorded among patients receiving concomitant nitrates [see Contraindications (4.1)]. Figure 1: Mean Change from Baseline in Sitting Systolic Blood Pressure, Healthy Volunteers. Effects of VIAGRA on Blood Pressure When Nitroglycerin is Subsequently Administered: Based on the pharmacokinetic profile of a single 100 mg oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2 ng/mL (compared to peak plasma levels of approximately 440 ng/mL). In the following patients: age >65 years, hepatic impairment (e.g., cirrhosis), severe renal impairment (e.g., creatinine clearance <30 mL/min), and concomitant use of erythromycin or strong CYP3A4 inhibitors, 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 co-administered at this time point [see Contraindications (4.1)].

Organic Nitrates, Nitrites, and Nitric Oxide Donors

Effects of VIAGRA on Blood Pressure When Co-administered with Alpha-Blockers: Three double-blind, placebo-controlled, randomized, two-way crossover studies were conducted to assess the interaction of VIAGRA with doxazosin, an alpha-adrenergic blocking agent. In the first study, a single oral dose of VIAGRA 100 mg or matching placebo was administered in a 2-period crossover design to 4 generally healthy males with benign prostatic hyperplasia (BPH). Following at least 14 consecutive daily doses of doxazosin, VIAGRA 100 mg or matching placebo was administered simultaneously sildenafil citrate 150 mg red pill with doxazosin. Following a review of the data from these first 4 subjects (details provided below), the VIAGRA dose was reduced to 25 mg. Thereafter, 17 subjects were treated with VIAGRA 25 mg or matching placebo in combination with doxazosin 4 mg (15 subjects) or doxazosin 8 mg (2 subjects). One patient discontinued the study prematurely due to an adverse event of hypotension following dosing with VIAGRA 50 mg. This patient had been taking minoxidil, a potent vasodilator, during the study. For the 19 subjects who received both VIAGRA 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 VIAGRA or matching placebo are shown in Figure 3. Figure 3: Mean Standing Systolic Blood Pressure Change from Baseline Blood pressure was measured after administration of VIAGRA 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 VIAGRA 50 mg and resolving after approximately 7.5 hours. There was one subject with a decrease from baseline in standing systolic BP >30mmHg following VIAGRA 50 mg and one subject with a decrease from baseline in standing systolic BP > 30 mmHg following both VIAGRA 50 mg and placebo. 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 VIAGRA 100 mg or matching placebo was administered in a 3-period crossover design to 20 generally healthy males with BPH.

• Sildenafil 60mg does not protect against sexually transmitted infections.
• Use condoms as a protective measure.
• Discuss any pre-existing conditions with your doctor.
• Its safety in women has not been established.

In dose period 1, subjects were administered open-label doxazosin and a single dose of VIAGRA 50 mg simultaneously, after 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 VIAGRA 50 mg), including no significant hemodynamic adverse events, were allowed to skip dose period 1.

52% of men experience some kind of erectile dysfunction throughout their life

Treatment with doxazosin continued for at least 7 days after dose period 1.