Concomitant use of sildenafil with nitrates in any form is contraindicated [see Contraindications (4)] . Concomitant use of sildenafil with strong CYP3A inhibitors is not recommended [see Clinical Pharmacology (12.3)] . Concomitant use of sildenafil with moderate-to-strong CYP3A inducers (such as bosentan) decreases the sildenafil exposure.
5.7 Priapism
No dose adjustment is required (including severe impairment CLcr <30 mL/min) [see Clinical Pharmacology (12.3)] . 10 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. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is not eliminated in the urine. 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.
Postmarketing Reports
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 to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7.Sildenafil Tablets, USP are formulated as blue colored, round, film-coated tablets for oral administration. Each tablet contains sildenafil citrate equivalent to 20 mg of sildenafil. Sildenafil is also marketed as VIAGRA ®for erectile dysfunction. Sildenafil Tablets, USP are formulated as blue colored, sildenafil citrate drug round, film-coated tablets for oral administration. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation.
Revatio Injection
In patients with PAH, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.Studies in vitrohave shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 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. Sildenafil is only about 10 times as potent for PDE5 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, PDE5 is also found in other tissues including vascular and visceral smooth muscle and in platelets. 8 USE IN SPECIFIC POPULATIONS 8.1 PregnancyRisk SummaryLimited 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. There are risks to the mother and fetus from untreated pulmonary arterial hypertension (see Clinical Considerations).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.
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Viagra Generic | 25mg | 180 + 6 Pills | 154.93€ 147.55€ | |
| Viagra Generic | 50mg | 20 Pills | 40.52€ 38.59€ | |
| Viagra Generic | 150mg | 360 + 10 Pills | 423.48€ 403.31€ | |
| Viagra Generic | 200mg | 60 + 4 Pills | 125.19€ 119.23€ | |
| Kamagra Oral Jelly | 100mg | 30 + 5 Sachets | 136.20€ 129.71€ | |
| Viagra Generic | 200mg | 10 Pills | 40.96€ 39.01€ | |
| Viagra Generic | 200mg | 180 + 10 Pills | 277.56€ 264.34€ | |
| Viagra Generic | 100mg | 60 + 4 Pills | 96.36€ 91.77€ | |
| Viagra Generic | 150mg | 270 + 10 Pills | 326.61€ 311.06€ | |
| Viagra Generic | 50mg | 90 + 6 Pills | 107.37€ 102.26€ | |
| Viagra Generic | 150mg | 60 + 4 Pills | 111.25€ 105.95€ | |
| Kamagra Polo | 100mg | 60 + 4 Pills | 189.39€ 180.37€ |
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
5.5 Hearing Loss
Concomitant use of sildenafil with nitrates in any form is contraindicated [see Contraindications (4)] . Concomitant use of sildenafil with strong CYP3A inhibitors is not recommended [see Clinical Pharmacology (12.3)] . Concomitant use of sildenafil with moderate-to-strong CYP3A inducers (such as bosentan) decreases the sildenafil exposure. 8 USE IN SPECIFIC POPULATIONS 8.1 PregnancyRisk SummaryLimited 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. There are risks to the mother and fetus from untreated pulmonary arterial hypertension (see Clinical Considerations).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.
4.1 Nitrates
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.Clinical ConsiderationsDisease-Associated Maternal and/or Embryo/Fetal RiskPregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death.DataAnimal DataNo 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).8.2 LactationRisk SummaryLimited published data from a case report describe the presence of sildenafil and its active metabolite in human milk. There is insufficient information about the effects of sildenafil on the breastfed infant and no information on the effects of sildenafil on milk production.
Clinical monitoring
Limited clinical data during lactation preclude a clear determination of the risk of sildenafil to an infant during lactation.8.4 Pediatric UseThe safety and effectiveness of sildenafil have not been established in pediatric patients younger than 1 year of age.Pediatric use information is approved for Viatris Specialty LLC's, REVATIO ®(sildenafil) tablets. However, due to Viatris Specialty LLC's marketing exclusivity rights, this drug product is not labeled with that information .8.5 Geriatric UseClinical studies of sildenafil did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 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)] .8.6 Patients with Hepatic ImpairmentNo dose adjustment for mild to moderate impairment is required. 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)] . 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.Clinical ConsiderationsDisease-Associated Maternal and/or Embryo/Fetal RiskPregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death.DataAnimal DataNo 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).8.2 LactationRisk SummaryLimited published data from a case report describe the presence of sildenafil and its active metabolite in human milk. There is insufficient information about the effects of sildenafil on the breastfed infant and no information on the effects of sildenafil on milk production. Limited clinical data during lactation preclude a clear determination of the risk of sildenafil to an infant during lactation.8.4 Pediatric UseThe safety and effectiveness of sildenafil have not been established in pediatric patients younger than 1 year of age.Pediatric use information is approved for Viatris Specialty LLC's, REVATIO ®(sildenafil) tablets. However, due to Viatris Specialty LLC's marketing exclusivity rights, this drug product is not labeled with that information .8.5 Geriatric UseClinical studies of sildenafil did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 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)] .8.6 Patients with Hepatic ImpairmentNo dose adjustment for mild to moderate impairment is required. 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.
| Storage Requirement | Temperature Range | Light Exposure | Humidity Control | Notes |
|---|---|---|---|---|
| Room Temperature | 20–25°C (68–77°F) | Keep away from direct sunlight | Keep in a dry place | Keep out of reach of children |
| Avoid Humidity | ≤60% RH | Store in original container | Avoid bathroom storage | Protect from moisture |
| Temperature Fluctuations | Avoid extreme temperatures | - | - | Prevent degradation |
There are risks to the mother and fetus from untreated pulmonary arterial hypertension (see Clinical Considerations).Animal reproduction studies conducted with sildenafil sildenafil citrate 200mg price 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.
INFORMATION ABOUT SILDENAFIL
The inhibition of PDE5 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 on Hemodynamic MeasuresAdultsPatients on all sildenafil doses achieved a statistically significant reduction in mean pulmonary arterial pressure (mPAP) compared to those on placebo in a study with no background vasodilators [see SUPER-1 in Clinical Studies (14)] . Data on other hemodynamic measures for the sildenafil 20 mg three times a day and placebo dosing regimens is displayed in Table 2. The relationship between these effects and improvements in 6-minute walk distance is unknown.Table 2. Changes from Baseline in Hemodynamic Parameters at Week 12 [mean (95% CI)] for the Sildenafil 20 mg Three Times a Day and Placebo GroupmPAP = mean pulmonary arterial pressure; PVR = pulmonary vascular resistance; SVR = systemic vascular resistance; RAP = right atrial pressure; CO = cardiac output; HR = heart rate. *The number of patients per treatment group varied slightly for each parameter due to missing assessments.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). 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.
- Special populations require careful consideration before prescribing.
- In elderly patients (65+), clearance may be reduced; start with a lower dose.
- No dose adjustment is typically needed for patients with mild renal impairment.
- For moderate renal impairment (CrCl 30-80 mL/min), caution is advised.
- In severe renal impairment (CrCl <30 mL/min), a 25mg dose is often recommended.
- For hepatic impairment (Child-Pugh A and B), a 25mg starting dose is advised.
- Sildenafil is not recommended for patients with severe hepatic impairment.
- Safety and efficacy in pediatric patients for ED have not been established.
- Revatio is approved for pediatric PAH patients aged 1 year and older.
- The dose for pediatric PAH is based on body weight and must be carefully calculated.
- Use during pregnancy is only for PAH and requires a careful risk/benefit analysis.
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.
8.2 Lactation
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. There are risks to the mother and fetus from untreated pulmonary arterial hypertension (see Clinical Considerations).Animal reproduction studies conducted with sildenafil sildenafil citrate 200mg price 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. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
5.8 Effects on Bleeding
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. Limited clinical data during lactation preclude a clear determination of the risk of sildenafil to an infant during lactation.
8.2 Lactation
The safety and effectiveness of sildenafil have not been established in pediatric patients younger than 1 year of age. Clinical studies of sildenafil did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. 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. Severe impairment has not been studied [see Clinical Pharmacology (12.3)] . Limited clinical data during lactation preclude a clear determination of the risk of sildenafil to an infant during lactation. The safety and effectiveness of sildenafil have not been established in pediatric patients younger than 1 year of age. Clinical studies of sildenafil did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. 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. 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)] .
- In case of overdose, standard supportive measures should be employed.
- Symptoms of overdose are expected to be an extension of common side effects.
- Severe hypotension could occur and may require active cardiovascular support.
- Hemodialysis is not expected to accelerate clearance of sildenafil.
- The primary metabolite, N-desmethyl sildenafil, is also not significantly dialyzable.
- Management of priapism may require corporal irrigation or surgical intervention.
- There is no specific antidote for sildenafil overdose.
- If an overdose is suspected, contact a poison control center immediately.
- Provide the medical professional with the amount ingested and the time.
- Keep the patient hydrated and monitor vital signs closely.
- Ingestions in children require immediate emergency medical attention.
10 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. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is not eliminated in the urine. 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. 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 to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7.Sildenafil Tablets, USP are formulated as blue colored, round, film-coated tablets for oral administration. Each tablet contains sildenafil citrate equivalent to 20 mg of sildenafil. Sildenafil is also marketed as VIAGRA ®for erectile dysfunction. Sildenafil Tablets, USP are formulated as blue colored, sildenafil citrate drug round, film-coated tablets for oral administration. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation. In patients with PAH, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.Studies in vitrohave shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 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.
Why is this medication prescribed?
Sildenafil is only about 10 times as potent for PDE5 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, PDE5 is also found in other tissues including vascular and visceral smooth muscle and in platelets. The inhibition of PDE5 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 on Hemodynamic MeasuresAdultsPatients on all sildenafil doses achieved a statistically significant reduction in mean pulmonary arterial pressure (mPAP) compared to those on placebo in a study with no background vasodilators [see SUPER-1 in Clinical Studies (14)] . Data on other hemodynamic measures for the sildenafil 20 mg three times a day and placebo dosing regimens is displayed in Table 2. The relationship between these effects and improvements in 6-minute walk distance is unknown.Table 2. Changes from Baseline in Hemodynamic Parameters at Week 12 [mean (95% CI)] for the Sildenafil 20 mg Three Times a Day and Placebo GroupmPAP = mean pulmonary arterial pressure; PVR = pulmonary vascular resistance; SVR = systemic vascular resistance; RAP = right atrial pressure; CO = cardiac output; HR = heart rate. *The number of patients per treatment group varied slightly for each parameter due to missing assessments.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).