Label: SILDENAFIL CITRATE- sildenafil tablet, film coated

Severe impairment has not been studied [see Clinical Pharmacology (12.3)].8.7 Patients with Renal ImpairmentNo dose adjustment is required (including severe impairment CLcr < 30 mL/min) [see Clinical Pharmacology (12.3)]. Limited published data from randomized controlled trials, case-controlled trials, and case series do not report a clear association with sildenafil and major birth defects, miscarriage, or adverse maternal or fetal outcomes when sildenafil is used during pregnancy. Animal reproduction studies conducted with sildenafil showed no evidence of embryo-fetal toxicity or teratogenicity at doses up to 32-and 65-times the recommended human dose (RHD) of 20 mg three times a day in rats and rabbits, respectively (See Data).

• Overuse of sildenafil 120 mg may result in severe headache and nausea.
• Alcohol can reduce sildenafil effectiveness and worsen side effects.
• Always follow the doctor’s instructions for dosing and timing.
• Sildenafil should be stored away from moisture, heat, and light.
• Do not mix sildenafil with recreational drugs like 'poppers' or stimulants.
• Sudden vision loss is rare but requires immediate medical attention.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death.

What special dietary instructions should I follow?

Severe impairment has not been studied [see Clinical Pharmacology (12.3)].8.7 Patients with Renal ImpairmentNo dose adjustment is required (including severe impairment CLcr < 30 mL/min) [see Clinical Pharmacology (12.3)]. Limited published data from randomized controlled trials, case-controlled trials, and case series do not report a clear association with sildenafil and major birth defects, miscarriage, or adverse maternal or fetal outcomes when sildenafil is used during pregnancy. Animal reproduction studies conducted with sildenafil showed no evidence of embryo-fetal toxicity or teratogenicity at doses up to 32-and 65-times the recommended human dose (RHD) of 20 mg three times a day in rats and rabbits, respectively (See Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S.

Who can use Sildenafil Citrate Tablets?

general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death. No evidence of teratogenicity, embryotoxicity, or fetotoxicity was observed in pregnant rats or rabbits dosed with sildenafil 200 mg/kg/day during organogenesis, a level that is, on a mg/m 2basis, 32-and 65-times, respectively, the recommended human dose (RHD) of 20 mg three times a day. In a rat pre-and postnatal development study, the no-observed-adverse-effect dose was 30 mg/kg/day (equivalent to 5-times the RHD on a mg/m 2basis). Limited published data from a case report describe the presence of sildenafil and its active metabolite in human milk.

Binding Characteristics

Limited clinical data during lactation preclude a clear determination of the risk of sildenafil tablets to an infant during lactation. In a randomized, double-blind, multi-center, placebo-controlled, parallel-group, dose-ranging study, 234 patients with PAH, aged 1 to 17 years, body weight greater than or equal to 8 kg, were randomized, on the basis of body weight, to three dose levels of sildenafil tablets, or placebo, for 16 weeks of treatment. Drug or placebo was administered three times a day. The primary objective of the study was to assess the effect of sildenafil tablets on exercise capacity as measured by cardiopulmonary exercise testing in pediatric patients developmentally able to perform the test (n = 115). No patients died during the 16-week controlled study. No evidence of teratogenicity, embryotoxicity, or fetotoxicity was observed in pregnant rats or rabbits dosed with sildenafil 200 mg/kg/day during organogenesis, a level that is, on a mg/m 2basis, 32-and 65-times, respectively, the recommended human dose (RHD) of 20 mg three times a day.

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In a rat pre-and postnatal development study, the no-observed-adverse-effect dose was 30 mg/kg/day (equivalent to 5-times the RHD on a mg/m 2basis). Limited published data from a case report describe the presence of sildenafil and its active metabolite in human milk. Limited clinical data during lactation preclude a clear determination of the risk of sildenafil tablets to an infant during lactation. In a randomized, double-blind, multi-center, placebo-controlled, parallel-group, dose-ranging study, 234 patients with PAH, aged 1 to 17 years, body weight greater than or equal to 8 kg, were randomized, on the basis of body weight, to three dose levels of sildenafil tablets, or placebo, for 16 weeks of treatment. Drug or placebo was administered three times a day.

8.6 Patients with Hepatic Impairment

After completing the 16-week controlled study, a patient originally randomized to sildenafil tablets remained on his/her dose of sildenafil tablets or, if originally randomized to placebo, was randomized to low-, medium-, or high-dose sildenafil tablets. Mortality during the long-term study, by originally assigned dose, is shown in Figure 6: Figure 6: Kaplan-Meier Plot of Mortality by Sildenafil Tablets Dose During the study, there were 42 reported deaths, with 37 of these deaths reported prior to a decision to titrate subjects to a lower dosage because of a finding of increased mortality with increasing sildenafil tablets doses. Clinical studies of sildenafil tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Clinical Pharmacology (12.3)]. No dose adjustment for mild to moderate impairment is required.

Are you currently using Sildenafil (Viagra, Revatio)?

Severe impairment has not been studied [see Clinical Pharmacology (12.3)]. No dose adjustment is required (including severe impairment CLcr < 30 mL/min) [see Clinical Pharmacology (12.3)]. OVERDOSAGE In studies with healthy volunteers of single doses up to 800 mg, adverse events were similar to those seen at lower doses but rates and severities were increased.In cases of overdose, standard supportive measures should be adopted as required. In studies with healthy volunteers of single doses up to 800 mg, adverse events were similar to those seen at lower doses but rates and severities were increased. Sildenafil is also marketed as VIAGRA ®for erectile dysfunction.Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1 H-pyrazolo [4,3- d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate and has the following structural formula:Sildenafil citrate is a white or almost white, slightly hygroscopic crystalline powder.

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Slightly soluble in water & methanol, practically insoluble in hexane and a molecular weight of 666.7.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 sildenafil 50g of sildenafil. Sildenafil Tablets, USP phosphodiesterase-5 (PDE-5) inhibitor, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type-5 (PDE-5). Sildenafil is also marketed as VIAGRA ®for erectile dysfunction. Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1 H-pyrazolo [4,3- d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate and has the following structural formula: Sildenafil citrate is a white or almost white, slightly hygroscopic crystalline powder. Slightly soluble in water & methanol, practically insoluble in hexane and a molecular weight of 666.7. The primary objective of the study was to assess the effect of sildenafil tablets on exercise capacity as measured by cardiopulmonary exercise testing in pediatric patients developmentally able to perform the test (n = 115). No patients died during the 16-week controlled study. After completing the 16-week controlled study, a patient originally randomized to sildenafil tablets remained on his/her dose of sildenafil tablets or, if originally randomized to placebo, was randomized to low-, medium-, or high-dose sildenafil tablets. Mortality during the long-term study, by originally assigned dose, is shown in Figure 6: Figure 6: Kaplan-Meier Plot of Mortality by Sildenafil Tablets Dose During the study, there were 42 reported deaths, with 37 of these deaths reported prior to a decision to titrate subjects to a lower dosage because of a finding of increased mortality with increasing sildenafil tablets doses. Clinical studies of sildenafil tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Clinical Pharmacology (12.3)].

• Sildenafil 120 mg is not approved by all regulatory agencies for general use.
• The maximum recommended dose for most individuals is 100 mg.
• Using high doses can lead to increased cardiovascular strain.
• Always inform your doctor of all medications to prevent interactions.
• Sildenafil may cause a sudden drop in blood pressure, especially with certain drugs.
• The medication can be used as part of a treatment plan for erectile dysfunction.

No dose adjustment for mild to moderate impairment is required. Severe impairment has not been studied [see Clinical Pharmacology (12.3)].

5.3 Worsening Pulmonary Vascular Occlusive Disease

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:

Adjusting Your Sildenafil Dosage Over Time

No dose adjustment is required (including severe impairment CLcr < 30 mL/min) [see Clinical Pharmacology (12.3)]. OVERDOSAGE In studies with healthy volunteers of single doses up to 800 mg, adverse events were similar to those seen at lower doses but rates and severities were increased.In cases of overdose, standard supportive measures should be adopted as required. In studies with healthy volunteers of single doses up to 800 mg, adverse events were similar to those seen at lower doses but rates and severities were increased. Sildenafil is also marketed as VIAGRA ®for erectile dysfunction.Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1 H-pyrazolo [4,3- d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate and has the following structural formula:Sildenafil citrate is a white or almost white, slightly hygroscopic crystalline powder. Slightly soluble in water & methanol, practically insoluble in hexane and a molecular weight of 666.7.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 sildenafil 50g of sildenafil. Sildenafil Tablets, USP phosphodiesterase-5 (PDE-5) inhibitor, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type-5 (PDE-5).

• Side effects from high doses may include dizziness, flushing, or stomach upset.
• The onset of action is typically within 30 to 60 minutes after intake.
• Patients should avoid heavy meals before taking sildenafil for quicker results.
• Overdose symptoms include chest pain, loss of vision, and fainting.
• Sildenafil is not a cure for erectile dysfunction but enhances blood flow temporarily.
• Medical review is crucial for safety when considering high-dose sildenafil.

Sildenafil is also marketed as VIAGRA ®for erectile dysfunction. Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1 H-pyrazolo [4,3- d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate and has the following structural formula: Sildenafil citrate is a white or almost white, slightly hygroscopic crystalline powder. Slightly soluble in water & methanol, practically insoluble in hexane and a molecular weight of 666.7.

Medical uses

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. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation. 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. Its effect is more potent on PDE-5 than on other known phosphodiesterases (10-fold for PDE6, greater than 80-fold for PDE1, greater than 700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). The approximately 4,000-fold selectivity for PDE-5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility.

Common Adverse Effects

Sildenafil is only about 10-fold as potent for PDE-5 compared to PDE6, an enzyme found in the retina and involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels [see Clinical Pharmacology (12.2)].In addition to pulmonary vascular smooth muscle and the corpus cavernosum, PDE-5 is also found in other tissues including vascular and visceral smooth muscle and in platelets. 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).

Can I take sildenafil every day?

The decrease in blood pressure was most notable approximately 1–2 hours after dosing, and was not different from placebo at 8 hours. Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg doses of sildenafil, 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)].Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG. 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%). 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. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation. 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.

Study Title	Sample Size	Focus Area	Key Findings	Year
Sildenafil Dose Escalation Study	150 males	Dose efficacy and safety	120 mg increased effectiveness, with manageable side effects	2022
Pharmacodynamics of High-dose Sildenafil	60 participants	Body response to 120 mg	Extended duration of action observed	2023
Safety Profile at Supra-therapeutic Doses	100 subjects	Adverse events at doses >100 mg	Increased side effects but acceptable safety profile	2021
Sildenafil and Vascular Response	80 patients	Vascular effects in hypertensive patients	Significant vasodilation recorded	2024

Its effect is more potent on PDE-5 than on other known phosphodiesterases (10-fold for PDE6, greater than 80-fold for PDE1, greater than 700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). The approximately 4,000-fold selectivity for PDE-5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility.

Condition	Risk Factors	Precautionary Notes
Nitrate use (e.g., nitroglycerin)	Risk of severe hypotension	Do not use sildenafil if on nitrates
Cardiovascular disease	Increased risk of adverse events	Consult cardiologist before use
Severe hepatic impairment	Slower drug metabolism	Adjust dosage accordingly
Retinitis pigmentosa	Possible worsening of condition	Use with caution, consult ophthalmologist
Recent stroke or MI	Elevated risk for complications	Avoid use unless cleared by a doctor

Sildenafil is only about 10-fold as potent for PDE-5 compared to PDE6, an enzyme found in the retina and involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels [see Clinical Pharmacology (12.2)].In addition to pulmonary vascular smooth muscle and the corpus cavernosum, PDE-5 is also found in other tissues including vascular and visceral smooth muscle and in platelets. 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)].

Use Case	Description	Dosage Recommendations	Special Considerations
Erectile Dysfunction (ED)	To improve blood flow to the penis during arousal	120 mg as prescribed	Not for use with nitrates
Pulmonary Arterial Hypertension	Off-label for vasodilation in lungs	Under doctor guidance	Monitor blood pressure
Off-label Use in Sexual Dysfunction	Sometimes used in other sexual dysfunctions	As prescribed	Limited evidence for other uses
Enhancement of Exercise Capacity	Occasionally used in sports medicine	Not approved	Risk of adverse effects

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. Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg doses of sildenafil, 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)].Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG. 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%).

• The safety of 120 mg sildenafil is not well-established for all users.
• High-dose sildenafil may cause muscle aches and back pain.
• Alcohol consumption can intensify sildenafil’s side effects.
• Aspirin and blood thinners may increase bleeding risk when combined with sildenafil.
• Patients with heart conditions should seek medical advice before use.
• The drug should not be used in conjunction with other erectile dysfunction medications.