Sildenafil Oral

Sildenafil tablets: Sildenafil tablets is white round, biconvex film coated tablets, debossed with R on one side and 20 on the other, containing sildenafil citrate equivalent to 20 mg of sildenafil. In patients with PAH, this can lead to vasodilatation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.Studies in vitro have shown that sildenafil is selective for PDE-5. The inhibition of PDE-5 in these tissues by sildenafil may be the basis for the enhanced platelet anti-aggregatory activity of nitric oxide observed in vitro, and the mild peripheral arterial-venous dilatation in vivo.12.2 PharmacodynamicsEffects of Sildenafil tablets on Hemodynamic MeasuresPatients on all sildenafil tablets doses achieved a statistically significant reduction in mean pulmonary arterial pressure (mPAP) compared to those on placebo in a study with no background vasodilators [ Study 1 in Clinical Studies (14)].

5.7 Priapism

Data on other hemodynamic measures for the sildenafil tablets 20 mg three times a day and placebo dosing regimens is displayed in Table 3. The relationship between these effects and improvements in 6-minute walk distance is unknown.In another study evaluating lower doses of sildenafil 1 mg, 5 mg and 20 mg [ Study 3 in Clinical Studies (14)] , there were no significant differences in the effects on hemodynamic variables between doses.Effects of Sildenafil on Blood PressureSingle oral doses of sildenafil 100 mg administered to healthy volunteers produced decreases in supine blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8/5 mmHg). The decrease in blood pressure was most notable approximately 1–2 hours after dosing, and was not different from placebo at 8 hours. After chronic dosing of 80 mg three times a day to patients with PAH, no clinically relevant effects on ECG were reported.After chronic dosing of 80 mg three times a day sildenafil to healthy volunteers, the largest mean change from baseline in supine systolic and supine diastolic blood pressures was a decrease of 9.0 mmHg and 8.4 mmHg, respectively.After chronic dosing of 80 mg three times a day sildenafil to patients with systemic hypertension, the mean change from baseline in systolic and diastolic blood pressures was a decrease of 9.4 mmHg and 9.1 mmHg, respectively.After chronic dosing of 80 mg three times a day sildenafil to patients with PAH, lesser reductions than above in systolic and diastolic blood pressures were observed (a decrease in both of 2 mmHg).Effects of Sildenafil tabletson VisionAt single oral doses of 100 mg and 200 mg, transient dose-related impairment of color discrimination (blue/green) was detected using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels.

An evaluation of visual function at doses up to 200 mg revealed no effects of sildenafil tablets on visual acuity, intraocular pressure, or pupillometry.12.3 PharmacokineticsSildenafil tablets is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (25–63%). When sildenafil tablets is taken with a high-fat meal, the rate of absorption is reduced, with a mean delay in T maxof 60 minutes and a mean reduction in C maxof 29%.

• The usual starting dose of sildenafil for ED is 50 mg, but 20 mg may be prescribed for some patients.
• Prescription requirements ensure safe usage and proper dosing based on health conditions.
• Always follow a doctor’s instructions when taking sildenafil 20 mg.

Protein binding is independent of total drug concentrations.Metabolism and ExcretionSildenafil is cleared predominantly by the CYP3A (major route) and cytochrome P450 2C9 (CYP2C9, minor route) hepatic microsomal isoenzymes. In healthy volunteers, plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil, so that the metabolite accounts for about 20% of sildenafil's pharmacologic effects. None of these factors had a significant impact on sildenafil pharmacokinetics in patients with PAH.In patients with PAH, the average steady-state concentrations were 20–50% higher when compared to those of healthy volunteers. Both findings suggest a lower clearance and/or a higher oral bioavailability of sildenafil in patients with PAH compared sildenafil citrates to healthy volunteers.Geriatric PatientsHealthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 84% and 107% higher plasma concentrations of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy younger volunteers (18–45 years). Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively.Renal ImpairmentIn volunteers with mild (CLcr = 50–80 mL/min) and moderate (CLcr = 30–49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of sildenafil (50 mg) was not altered. In addition, N-desmethyl metabolite AUC and C maxvalues were significantly increased 200 % and 79 %, respectively, in subjects with severe renal impairment compared to subjects with normal renal function.Hepatic ImpairmentIn volunteers with mild to moderate hepatic cirrhosis (Child-Pugh class A and B), sildenafil clearance was reduced, resulting in increases in AUC (84%) and C max(47%) compared to age-matched volunteers with no hepatic impairment. Patients with severe hepatic impairment (Child-Pugh class C) have not been studied.Drug Interaction StudiesIn vitrostudiesSildenafil metabolism is principally mediated by the CYP3A (major route) and CYP2C9 (minor route) cytochrome P450 isoforms.

5.3 Worsening Pulmonary Vascular Occlusive Disease

Patients with severe hepatic impairment (Child-Pugh class C) have not been studied.Drug Interaction StudiesIn vitrostudiesSildenafil metabolism is principally mediated by the CYP3A (major route) and CYP2C9 (minor route) cytochrome P450 isoforms. Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance.Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A (IC50 greater than 150 µM).Sildenafil is not expected to affect the pharmacokinetics of compounds which are substrates of these CYP enzymes at clinically relevant concentrations.In vivostudiesThe effects of other drugs on sildenafil pharmacokinetics and the effects of sildenafil on the exposure to other drugs are shown in Figure 7 and Figure 8, respectively.Figure 7. Effects of Other Drugs on Sildenafil PharmacokineticsFigure 8 Effects of Sildenafil on Other DrugsCYP3A Inhibitors and Beta BlockersPopulation pharmacokinetic analysis of data from patients in clinical trails indicated an approximately 30% reduction in sildenafil clearance when it was co-administered with mild/moderate CYP3A inhibitors and an approximately 34% reductions in sildenafil clearance when co-administered with beta-blockers. This concentration range covers the same increased sildenafil exposure observed in specifically-designed drug interaction studies with CYP3A inhibitors (except for potent inhibitors such as ketoconazole, itraconazole, and ritonavir).CYP3A4 inducers including bosentanConcomitant administration of potent CYP3A inducers is expected to cause substantial decreases in plasma levels of sildenafil.Population pharmacokinetic analysis of data from patients in clinical trials indicated an approximately 3-fold the sildenafil clearance when it was co-administered with mild CYP3A inducers.EpoprostenolThe mean reduction of sildenafil (80 mg three times a day) bioavailability when co-administered with epoprostenol was 28%, resulting in about 22% lower mean average steady state concentrations. In patients with PAH, this can lead to vasodilatation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.

4.1 Nitrates

Effects of Sildenafil tablets on Hemodynamic Measures Patients on all sildenafil tablets doses achieved a statistically significant reduction in mean pulmonary arterial pressure (mPAP) compared to those on placebo in a study with no background vasodilators [ Study 1 in Clinical Studies (14)]. In another study evaluating lower doses of sildenafil 1 mg, 5 mg and 20 mg [ Study 3 in Clinical Studies (14)] , there were no significant differences in the effects on hemodynamic variables between doses. An evaluation of visual function at doses up to 200 mg revealed no effects of sildenafil tablets on visual acuity, intraocular pressure, or pupillometry. Sildenafil tablets is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (25–63%). In patients with PAH, the average steady-state concentrations were 20–50% higher when sildenafil citrate tablets 150 mg compared to those of healthy volunteers.

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Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 84% and 107% higher plasma concentrations of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy younger volunteers (18–45 years). In volunteers with mild (CLcr = 50–80 mL/min) and moderate (CLcr = 30–49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of sildenafil (50 mg) was not altered. In addition, N-desmethyl metabolite AUC and C maxvalues were significantly increased 200 % and 79 %, respectively, in subjects with severe renal impairment compared to subjects with normal renal function. Effects of Other Drugs on Sildenafil Pharmacokinetics Figure 8 Effects of Sildenafil on Other Drugs Population pharmacokinetic analysis of data from patients in clinical trails indicated an approximately 30% reduction in sildenafil clearance when it was co-administered with mild/moderate CYP3A inhibitors and an approximately 34% reductions in sildenafil clearance when co-administered with beta-blockers. Population pharmacokinetic analysis of data from patients in clinical trials indicated an approximately 3-fold the sildenafil clearance when it was co-administered with mild CYP3A inducers. Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance.Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A (IC50 greater than 150 µM).Sildenafil is not expected to affect the pharmacokinetics of compounds which are substrates of these CYP enzymes at clinically relevant concentrations.In vivostudiesThe effects of other drugs on sildenafil pharmacokinetics and the effects of sildenafil on the exposure to other drugs are shown in Figure 7 and Figure 8, respectively.Figure 7.

2. Sildenafil Tablets Dosage and Administration

Sildenafil tablets: Sildenafil tablets is white round, biconvex film coated tablets, debossed with R on one side and 20 on the other, containing sildenafil citrate equivalent to 20 mg of sildenafil. In patients with PAH, this can lead to vasodilatation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.Studies in vitro have shown that sildenafil is selective for PDE-5. The inhibition of PDE-5 in these tissues by sildenafil may be the basis for the enhanced platelet anti-aggregatory activity of nitric oxide observed in vitro, and the mild peripheral arterial-venous dilatation in vivo.12.2 PharmacodynamicsEffects of Sildenafil tablets on Hemodynamic MeasuresPatients on all sildenafil tablets doses achieved a statistically significant reduction in mean pulmonary arterial pressure (mPAP) compared to those on placebo in a study with no background vasodilators [ Study 1 in Clinical Studies (14)]. Data on other hemodynamic measures for the sildenafil tablets 20 mg three times a day and placebo dosing regimens is displayed in Table 3. The relationship between these effects and improvements in 6-minute walk distance is unknown.In another study evaluating lower doses of sildenafil 1 mg, 5 mg and 20 mg [ Study 3 in Clinical Studies (14)] , there were no significant differences in the effects on hemodynamic variables between doses.Effects of Sildenafil on Blood PressureSingle oral doses of sildenafil 100 mg administered to healthy volunteers produced decreases in supine blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8/5 mmHg).

Warnings for people with certain health conditions

The decrease in blood pressure was most notable approximately 1–2 hours after dosing, and was not different from placebo at 8 hours. After chronic dosing of 80 mg three times a day to patients with PAH, no clinically relevant effects on ECG were reported.After chronic dosing of 80 mg three times a day sildenafil to healthy volunteers, the largest mean change from baseline in supine systolic and supine diastolic blood pressures was a decrease of 9.0 mmHg and 8.4 mmHg, respectively.After chronic dosing of 80 mg three times a day sildenafil to patients with systemic hypertension, the mean change from baseline in systolic and diastolic blood pressures was a decrease of 9.4 mmHg and 9.1 mmHg, respectively.After chronic dosing of 80 mg three times a day sildenafil to patients with PAH, lesser reductions than above in systolic and diastolic blood pressures were observed (a decrease in both of 2 mmHg).Effects of Sildenafil tabletson VisionAt single oral doses of 100 mg and 200 mg, transient dose-related impairment of color discrimination (blue/green) was detected using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. An evaluation of visual function at doses up to 200 mg revealed no effects of sildenafil tablets on visual acuity, intraocular pressure, or pupillometry.12.3 PharmacokineticsSildenafil tablets is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (25–63%). When sildenafil tablets is taken with a high-fat meal, the rate of absorption is reduced, with a mean delay in T maxof 60 minutes and a mean reduction in C maxof 29%. Protein binding is independent of total drug concentrations.Metabolism and ExcretionSildenafil is cleared predominantly by the CYP3A (major route) and cytochrome P450 2C9 (CYP2C9, minor route) hepatic microsomal isoenzymes.

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In healthy volunteers, plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil, so that the metabolite accounts for about 20% of sildenafil's pharmacologic effects. None of these factors had a significant impact on sildenafil pharmacokinetics in patients with PAH.In patients with PAH, the average steady-state concentrations were 20–50% higher when compared to those of healthy volunteers. Both findings suggest a lower clearance and/or a higher oral bioavailability of sildenafil in patients with PAH compared sildenafil citrates to healthy volunteers.Geriatric PatientsHealthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 84% and 107% higher plasma concentrations of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy younger volunteers (18–45 years). Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively.Renal ImpairmentIn volunteers with mild (CLcr = 50–80 mL/min) and moderate (CLcr = 30–49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of sildenafil (50 mg) was not altered. In addition, N-desmethyl metabolite AUC and C maxvalues were significantly increased 200 % and 79 %, respectively, in subjects with severe renal impairment compared to subjects with normal renal function.Hepatic ImpairmentIn volunteers with mild to moderate hepatic cirrhosis (Child-Pugh class A and B), sildenafil clearance was reduced, resulting in increases in AUC (84%) and C max(47%) compared to age-matched volunteers with no hepatic impairment. Effects of Other Drugs on Sildenafil PharmacokineticsFigure 8 Effects of Sildenafil on Other DrugsCYP3A Inhibitors and Beta BlockersPopulation pharmacokinetic analysis of data from patients in clinical trails indicated an approximately 30% reduction in sildenafil clearance when it was co-administered with mild/moderate CYP3A inhibitors and an approximately 34% reductions in sildenafil clearance when co-administered with beta-blockers. This concentration range covers the same increased sildenafil exposure observed in specifically-designed drug interaction studies with CYP3A inhibitors (except for potent inhibitors such as ketoconazole, itraconazole, and ritonavir).CYP3A4 inducers including bosentanConcomitant administration of potent CYP3A inducers is expected to cause substantial decreases in plasma levels of sildenafil.Population pharmacokinetic analysis of data from patients in clinical trials indicated an approximately 3-fold the sildenafil clearance when it was co-administered with mild CYP3A inducers.EpoprostenolThe mean reduction of sildenafil (80 mg three times a day) bioavailability when co-administered with epoprostenol was 28%, resulting in about 22% lower mean average steady state concentrations.

• Common side effects of sildenafil include headaches, flushing, and nasal congestion.
• Serious side effects are rare but require immediate medical attention.
• Patients should report any adverse reactions to their healthcare provider.

In patients with PAH, this can lead to vasodilatation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation. Effects of Sildenafil tablets on Hemodynamic Measures Patients on all sildenafil tablets doses achieved a statistically significant reduction in mean pulmonary arterial pressure (mPAP) compared to those on placebo in a study with no background vasodilators [ Study 1 in Clinical Studies (14)]. In another study evaluating lower doses of sildenafil 1 mg, 5 mg and 20 mg [ Study 3 in Clinical Studies (14)] , there were no significant differences in the effects on hemodynamic variables between doses. An evaluation of visual function at doses up to 200 mg revealed no effects of sildenafil tablets on visual acuity, intraocular pressure, or pupillometry. Sildenafil tablets is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (25–63%).

Side Effects

In patients with PAH, the average steady-state concentrations were 20–50% higher when sildenafil citrate tablets 150 mg compared to those of healthy volunteers. Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 84% and 107% higher plasma concentrations of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy younger volunteers (18–45 years).

10. Overdosage

NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilitySildenafil was not carcinogenic when administered to rats for up to 24 months at 60 mg/kg/day, a dose resulting in total systemic exposure (AUC) to unbound sildenafil and its major metabolite 33- and 37- times, for male and female rats respectively, the human exposure at the RHD of 20 mg three times a day. Sildenafil was not carcinogenic when administered to male and female mice for up to 21 and 18 months, respectively, at doses up to a maximally tolerated level of 10 mg/kg/day, a dose equivalent to the RHD on a mg/m 2basis.Sildenafil was negative in in vitrobacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitrohuman lymphocytes and in vivomouse micronucleus assays to detect clastogenicity.There was no impairment of fertility in male or female rats given up to 60 mg sildenafil/kg/day, a dose producing a total systemic exposure (AUC) to unbound sildenafil and its major metabolite of 19- and 38- times for males and females, respectively, the human exposure at the RHD of 20 mg three times a day.

2.1 Dosage Information

Drugs you should not use with sildenafil

In volunteers with mild (CLcr = 50–80 mL/min) and moderate (CLcr = 30–49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of sildenafil (50 mg) was not altered. In addition, N-desmethyl metabolite AUC and C maxvalues were significantly increased 200 % and 79 %, respectively, in subjects with severe renal impairment compared to subjects with normal renal function. Effects of Other Drugs on Sildenafil Pharmacokinetics Figure 8 Effects of Sildenafil on Other Drugs Population pharmacokinetic analysis of data from patients in clinical trails indicated an approximately 30% reduction in sildenafil clearance when it was co-administered with mild/moderate CYP3A inhibitors and an approximately 34% reductions in sildenafil clearance when co-administered with beta-blockers.

• Sildenafil 20 mg is a prescription medication used for erectile dysfunction.
• It helps increase blood flow to the penis during sexual activity.
• Typically prescribed for men with ED to improve sexual performance.

Population pharmacokinetic analysis of data from patients in clinical trials indicated an approximately 3-fold the sildenafil clearance when it was co-administered with mild CYP3A inducers. NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilitySildenafil was not carcinogenic when administered to rats for up to 24 months at 60 mg/kg/day, a dose resulting in total systemic exposure (AUC) to unbound sildenafil and its major metabolite 33- and 37- times, for male and female rats respectively, the human exposure at the RHD of 20 mg three times a day. Sildenafil was not carcinogenic when administered to male and female mice for up to 21 and 18 months, respectively, at doses up to a maximally tolerated level of 10 mg/kg/day, a dose equivalent to the RHD on a mg/m 2basis.Sildenafil was negative in in vitrobacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitrohuman lymphocytes and in vivomouse micronucleus assays to detect clastogenicity.There was no impairment of fertility in male or female rats given up to 60 mg sildenafil/kg/day, a dose producing a total systemic exposure (AUC) to unbound sildenafil and its major metabolite of 19- and 38- times for males and females, respectively, the human exposure at the RHD of 20 mg three times a day.