Bioequivalence and Bioavailability of an Orodispersible Tablet of Sildenafil Citrate in Healthy Chinese Male Subjects

The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility.

• Sildenafil use should be disclosed to your healthcare provider.
• Not suitable for men with severe cardiovascular conditions.
• Ask about possible drug interactions before starting.
• Adjustments may be needed for older adults.
• Timing of medication is important for maximum effect.
• Monitoring for side effects helps prevent complications.
• Stop using sildenafil if health issues arise.
• Always follow professional medical advice.

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)] .

7.2 Alpha-blockers

In a 12-week, placebo-controlled clinical study and an open-label extension study (SUPER-1) in 277 sildenafil citrate-treated adults with PAH (WHO Group I) [see Clinical Studies (14)] the adverse reactions that were reported by at least 10% of sildenafil citrate-treated patients in any dosing group, and were more frequent in sildenafil citrate-treated patients than in placebo-treated patients are shown in Table 1. The overall frequency of discontinuation in sildenafil citrate-treated patients was 3% (20 mg and 40 mg three times a day) and 8% (80 mg three times a day). Most Common Adverse Reactions in Patients Treated with sildenafil tablets 20 mg, 40 mg, 80 mg and Placebo three times per day in SUPER-1 (More Frequent in sildenafil-Treated Patients than Placebo-Treated Patients) In a placebo-controlled fixed dose titration study (PACES-1) of sildenafil citrate (starting with recommended dose of 20 mg and increased to 40 mg and then 80 mg all three times a day) as an adjunct to intravenous epoprostenol in patients with PAH, no new safety issues were identified except for edema, which occurred in 25% of subjects in the combined sildenafil citrate + epoprostenol group canadian sildenafil citrate compared with 13% of subjects in the epoprostenol group [see Clinical Studies (14)]. In a study to assess the effects of multiple doses of sildenafil citrate on mortality in adults with PAH (StudyA1481324), the lower dose 5 mg TID group showed a higher observed number of deaths (all related to underlying disease/disease under study), serious adverse events, and severe adverse events than the 20 mg and 80 mg TID groups [see Clinical Studies (14)]. Overall, the safety data for sildenafil 80 mg TID dose in Study A1481324 was consistent with the established safety profile of sildenafil in previous adult PAH studies.

Destinations with risk

Sildenafil citrate was studied in a total of 234 PAH pediatric patients 1 to 17 years of age in a 16-week, double-blind placebo-controlled study (STARTS-1); 220 patients continued in a longterm extension study (STARTS-2). Erection increased was observed in 9% of patients treated with sildenafil in STARTS-1. No other new adverse reactions were identified in pediatric patients [see Use in Specific Populations (8.4)]. In postmarketing experience with sildenafil at doses indicated for erectile dysfunction, serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, pulmonary hemorrhage, and subarachnoid and intracerebral hemorrhages have been reported in temporal association with the use of the drug. It is not possible to determine whether these events are related directly to sildenafil, to sexual activity, to the patient's underlying cardiovascular disease, or to a combination of these or other factors. Effects of Sildenafil Citrate on Hemodynamic Measures Patients on all sildenafil citrate 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 tablets 20 mg three times a day and placebo dosing regimens is displayed in Table 2.

• Sildenafil tablets 125 mg are available by prescription only.
• They work by inhibiting the PDE5 enzyme.
• Do not mix sildenafil with alcohol to avoid adverse effects.
• Use with caution if you have heart or liver conditions.
• Sildenafil may interact with certain antibiotics.
• Be aware of potential side effects like flushing.
• Take sildenafil about 30-60 minutes before activity.
• Avoid using grapefruit juice while on sildenafil.

Changes from Baseline in Hemodynamic Parameters at Week 12 [mean (95% CI)] for the Sildenafil Tablets 20 mg Three Times a Day and Placebo Group mPAP = 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.

5. Warnings and Precautions

Clinical Considerations 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. Data Animal Data 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/m2 basis, 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/m2 basis). Risk Summary Limited published data from a case report describe the presence of sildenafil and its active metabolite in human milk. The safety and efficacy of Sildenafil citrate have been established in pediatric patients 1 to 17 years old, for the treatment of PAH (WHO Group I) to improve exercise ability and, in patients too young to perform standard exercising testing, pulmonary hemodynamics thought to underly improvements in exercise Use of sildenafil citrate for this indication is supported by evidence from adequate and well-controlled studies in adults with additional PK and safety data in pediatric patients aged 1 year and older [see Adverse Reactions (6.1), Clinical Studies (14)].

What should I tell my healthcare provider before taking sildenafil?

The safety and effectiveness of sildenafil citrate have not been established in pediatric patients younger than 1 year of age. During the conduct of the pediatric studies (STARTS-1 and STARTS-2) [see Clinical Studies(14)], an imbalance in the number of deaths was noted: 5/55 (9.1%), 10/74 (13.5%), and 22/100 (22%) in the sildenafil low, medium, and high dose groups, respectively. The causes of death were related to the progression of PAH. This safety observation in pediatrics was not confirmed in a study conducted in adults designed to evaluate this risk (Study A1481324). Given the beneficial effects on clinical worsening and death observed in adults with increasing doses (Study A1481324) and the expected similarity of disease in pediatrics and adults, a causal association for the observed dose-related effect on mortality in pediatric patients is unlikely, and therefore, the available data support dosing in pediatric patients >45 kg up to a maximum of 40 mg three times a day. Patients on sildenafil tablets medium and high dose groups achieved a dose related improvements in pulmonary vascular resistance index (PVRI) and mean pulmonary arterial pressure (mPAP) compared to those on placebo [see STARTS-1 in Clinical Studies (14)].

Dosage for Viagra

In general, dose selection for an elderly patient should be cautious, buy sildenafil citrate online canada reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Clinical Pharmacology (12.3)] . 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)] . 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.

Allergy warning

Sildenafil Tablets USP: Sildenafil citrate is formulated as white, film-coated round tablets for oral administration. Each tablet contains sildenafil citrate equivalent to 20 mg of sildenafil. In addition to the active ingredient, sildenafil citrate, each tablet contains the following inactive ingredients: croscarmellose sodium, dibasic calcium phosphate anhydrous, hypromellose, microcrystalline cellulose, sodium stearyl fumarate, titanium dioxide and triacetin. Studies in vitro have shown that sildenafil is selective for PDE5. 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). Improvements were observed with cardiac index in all three sildenafil tablets dose groups over placebo.

• Always use the lowest effective dose of sildenafil.
• Follow your doctor’s instructions carefully.
• Do not alter the dosage without consulting your doctor.
• Keep track of your health conditions and medications.
• Use sildenafil responsibly to prevent dependency.
• Seek prompt medical attention for prolonged erections.
• Consider lifestyle changes to improve ED symptoms.
• Education about sildenafil can improve treatment outcomes.

Data on other hemodynamic measures for the sildenafil tablets low, medium and high dose groups compared to placebo is displayed in Table 3.

2.5 Dosage Adjustments in Special Populations

NAION [see Warnings and Precautions (5.4), Patient Counseling Information (17)]. Concomitant use of sildenafil citrate with nitrates in any form is contraindicated [see Contraindications (4)] . Strong CYP3A Inhibitors Concomitant use of sildenafil citrate with strong CYP3A inhibitors is not recommended [see Clinical Pharmacology (12.3)]. Moderate-to-Strong CYP3A Inducers Concomitant use of Sildenafil citrate with moderate-to-strong CYP3A inducers (such as bosentan) decreases the sildenafil exposure. Reduce the dose of sildenafil tablets to 20 mg three times a day when discontinuing treatment with moderate-to-strong CYP3A inducers [see Clinical Pharmacology (12.3) and Clinical Studies (14)].

What are the most common side effects of sildenafil?

Risk Summary 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 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). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.